Factors governing the substitution of La3+ for Ca2+ and Mg2+ in metalloproteins: a DFT/CDM study.

PubMed

Dudev, Todor; Chang, Li-Ying; Lim, Carmay

2005-03-23

Trivalent lanthanide cations are extensively being used in biochemical experiments to probe various dication-binding sites in proteins; however, the factors governing the binding specificity of lanthanide cations for these binding sites remain unclear. Hence, we have performed systematic studies to evaluate the interactions between La3+ and model Ca2+ - and Mg2+ -binding sites using density functional theory combined with continuum dielectric methods. The calculations reveal the key factors and corresponding physical bases favoring the substitution of trivalent lanthanides for divalent Ca2+ and Mg2+ in holoproteins. Replacing Ca2+ or Mg2+ with La3+ is facilitated by (1) minimizing the solvent exposure and the flexibility of the metal-binding cavity, (2) freeing both carboxylate oxygen atoms of Asp/Glu side chains in the metal-binding site so that they could bind bidentately to La3+, (3) maximizing the number of metal-bound carboxylate groups in buried sites, but minimizing the number of metal-bound carboxylate groups in solvent-exposed sites, and (4) including an Asn/Gln side chain for sites lined with four Asp/Glu side chains. In proteins bound to both Mg2+ and Ca2+, La3+ would prefer to replace Ca2+, as compared to Mg2+. A second Mg2+-binding site with a net positive charge would hamper the Mg2+ --> La3+ exchange, as compared to the respective mononuclear site, although the La3+ substitution of the first native metal is more favorable than the second one. The findings of this work are in accord with available experimental data.

Solvent dielectric effect and side chain mutation on the structural stability of Burkholderia cepacia lipase active site: a quantum mechanical/molecular mechanics study.

PubMed

Tahan, A; Monajjemi, M

2011-12-01

Quantum mechanical and molecular dynamics methods were used to analyze the structure and stability of neutral and zwitterionic configurations of the extracted active site sequence from a Burkholderia cepacia lipase, histidyl-seryl-glutamin (His86-Ser87-Gln88) and its mutated form, histidyl-cysteyl-glutamin (His86-Cys87-Gln88) in vacuum and different solvents. The effects of solvent dielectric constant, explicit and implicit water molecules and side chain mutation on the structure and stability of this sequence in both neutral and zwitterionic forms are represented. The quantum mechanics computations represent that the relative stability of zwitterionic and neutral configurations depends on the solvent structure and its dielectric constant. Therefore, in vacuum and the considered non-polar solvents, the neutral form of the interested sequences is more stable than the zwitterionic form, while their zwitterionic form is more stable than the neutral form in the aqueous solution and the investigated polar solvents in most cases. However, on the potential energy surfaces calculated, there is a barrier to proton transfer from the positively charged ammonium group to the negatively charged carboxylat group or from the ammonium group to the adjacent carbonyl oxygen and or from side chain oxygen and sulfur to negatively charged carboxylat group. Molecular dynamics simulations (MD) were also performed by using periodic boundary conditions for the zwitterionic configuration of the hydrated molecules in a box of water molecules. The obtained results demonstrated that the presence of explicit water molecules provides the more compact structures of the studied molecules. These simulations also indicated that side chain mutation and replacement of sulfur with oxygen leads to reduction of molecular flexibility and packing.

Solvation thermodynamics of amino acid side chains on a short peptide backbone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hajari, Timir; Vegt, Nico F. A. van der, E-mail: vandervegt@csi.tu-darmstadt.de

The hydration process of side chain analogue molecules differs from that of the actual amino acid side chains in peptides and proteins owing to the effects of the peptide backbone on the aqueous solvent environment. A recent molecular simulation study has provided evidence that all nonpolar side chains, attached to a short peptide backbone, are considerably less hydrophobic than the free side chain analogue molecules. In contrast to this, the hydrophilicity of the polar side chains is hardly affected by the backbone. To analyze the origin of these observations, we here present a molecular simulation study on temperature dependent solvationmore » free energies of nonpolar and polar side chains attached to a short peptide backbone. The estimated solvation entropies and enthalpies of the various amino acid side chains are compared with existing side chain analogue data. The solvation entropies and enthalpies of the polar side chains are negative, but in absolute magnitude smaller compared with the corresponding analogue data. The observed differences are large; however, owing to a nearly perfect enthalpy-entropy compensation, the solvation free energies of polar side chains remain largely unaffected by the peptide backbone. We find that a similar compensation does not apply to the nonpolar side chains; while the backbone greatly reduces the unfavorable solvation entropies, the solvation enthalpies are either more favorable or only marginally affected. This results in a very small unfavorable free energy cost, or even free energy gain, of solvating the nonpolar side chains in strong contrast to solvation of small hydrophobic or nonpolar molecules in bulk water. The solvation free energies of nonpolar side chains have been furthermore decomposed into a repulsive cavity formation contribution and an attractive dispersion free energy contribution. We find that cavity formation next to the peptide backbone is entropically favored over formation of similar sized nonpolar side chain cavities in bulk water, in agreement with earlier work in the literature on analysis of cavity fluctuations at nonpolar molecular surfaces. The cavity and dispersion interaction contributions correlate quite well with the solvent accessible surface area of the nonpolar side chains attached to the backbone. This correlation however is weak for the overall solvation free energies owing to the fact that the cavity and dispersion free energy contributions are almost exactly cancelling each other.« less

Solvation thermodynamics of amino acid side chains on a short peptide backbone

NASA Astrophysics Data System (ADS)

Hajari, Timir; van der Vegt, Nico F. A.

2015-04-01

The hydration process of side chain analogue molecules differs from that of the actual amino acid side chains in peptides and proteins owing to the effects of the peptide backbone on the aqueous solvent environment. A recent molecular simulation study has provided evidence that all nonpolar side chains, attached to a short peptide backbone, are considerably less hydrophobic than the free side chain analogue molecules. In contrast to this, the hydrophilicity of the polar side chains is hardly affected by the backbone. To analyze the origin of these observations, we here present a molecular simulation study on temperature dependent solvation free energies of nonpolar and polar side chains attached to a short peptide backbone. The estimated solvation entropies and enthalpies of the various amino acid side chains are compared with existing side chain analogue data. The solvation entropies and enthalpies of the polar side chains are negative, but in absolute magnitude smaller compared with the corresponding analogue data. The observed differences are large; however, owing to a nearly perfect enthalpy-entropy compensation, the solvation free energies of polar side chains remain largely unaffected by the peptide backbone. We find that a similar compensation does not apply to the nonpolar side chains; while the backbone greatly reduces the unfavorable solvation entropies, the solvation enthalpies are either more favorable or only marginally affected. This results in a very small unfavorable free energy cost, or even free energy gain, of solvating the nonpolar side chains in strong contrast to solvation of small hydrophobic or nonpolar molecules in bulk water. The solvation free energies of nonpolar side chains have been furthermore decomposed into a repulsive cavity formation contribution and an attractive dispersion free energy contribution. We find that cavity formation next to the peptide backbone is entropically favored over formation of similar sized nonpolar side chain cavities in bulk water, in agreement with earlier work in the literature on analysis of cavity fluctuations at nonpolar molecular surfaces. The cavity and dispersion interaction contributions correlate quite well with the solvent accessible surface area of the nonpolar side chains attached to the backbone. This correlation however is weak for the overall solvation free energies owing to the fact that the cavity and dispersion free energy contributions are almost exactly cancelling each other.

Conditional solvation thermodynamics of isoleucine in model peptides and the limitations of the group-transfer model.

PubMed

Tomar, Dheeraj S; Weber, Valéry; Pettitt, B Montgomery; Asthagiri, D

2014-04-17

The hydration thermodynamics of the amino acid X relative to the reference G (glycine) or the hydration thermodynamics of a small-molecule analog of the side chain of X is often used to model the contribution of X to protein stability and solution thermodynamics. We consider the reasons for successes and limitations of this approach by calculating and comparing the conditional excess free energy, enthalpy, and entropy of hydration of the isoleucine side chain in zwitterionic isoleucine, in extended penta-peptides, and in helical deca-peptides. Butane in gauche conformation serves as a small-molecule analog for the isoleucine side chain. Parsing the hydrophobic and hydrophilic contributions to hydration for the side chain shows that both of these aspects of hydration are context-sensitive. Furthermore, analyzing the solute-solvent interaction contribution to the conditional excess enthalpy of the side chain shows that what is nominally considered a property of the side chain includes entirely nonobvious contributions of the background. The context-sensitivity of hydrophobic and hydrophilic hydration and the conflation of background contributions with energetics attributed to the side chain limit the ability of a single scaling factor, such as the fractional solvent exposure of the group in the protein, to map the component energetic contributions of the model-compound data to their value in the protein. But ignoring the origin of cancellations in the underlying components the group-transfer model may appear to provide a reasonable estimate of the free energy for a given error tolerance.

Contribution of TyrB26 to the Function and Stability of Insulin

PubMed Central

Pandyarajan, Vijay; Phillips, Nelson B.; Rege, Nischay; Lawrence, Michael C.; Whittaker, Jonathan; Weiss, Michael A.

2016-01-01

Crystallographic studies of insulin bound to receptor domains have defined the primary hormone-receptor interface. We investigated the role of TyrB26, a conserved aromatic residue at this interface. To probe the evolutionary basis for such conservation, we constructed 18 variants at B26. Surprisingly, non-aromatic polar or charged side chains (such as Glu, Ser, or ornithine (Orn)) conferred high activity, whereas the weakest-binding analogs contained Val, Ile, and Leu substitutions. Modeling of variant complexes suggested that the B26 side chains pack within a shallow depression at the solvent-exposed periphery of the interface. This interface would disfavor large aliphatic side chains. The analogs with highest activity exhibited reduced thermodynamic stability and heightened susceptibility to fibrillation. Perturbed self-assembly was also demonstrated in studies of the charged variants (Orn and Glu); indeed, the GluB26 analog exhibited aberrant aggregation in either the presence or absence of zinc ions. Thus, although TyrB26 is part of insulin's receptor-binding surface, our results suggest that its conservation has been enjoined by the aromatic ring's contributions to native stability and self-assembly. We envisage that such classical structural relationships reflect the implicit threat of toxic misfolding (rather than hormonal function at the receptor level) as a general evolutionary determinant of extant protein sequences. PMID:27129279

Side-chain-side-chain interactions and stability of the helical state

NASA Astrophysics Data System (ADS)

Zangi, Ronen

2014-01-01

Understanding the driving forces that lead to the stability of the secondary motifs found in proteins, namely α-helix and β-sheet, is a major goal in structural biology. The thermodynamic stability of these repetitive units is a result of a delicate balance between many factors, which in addition to the peptide chain involves also the solvent. Despite the fact that the backbones of all amino acids are the same (except of that of proline), there are large differences in the propensity of the different amino acids to promote the helical structure. In this paper, we investigate by explicit-solvent molecular dynamics simulations the role of the side chains (modeled as coarse-grained single sites) in stabilizing α helices in an aqueous solution. Our model systems include four (six-mer-nine-mer) peptide lengths in which the magnitude of the effective attraction between the side chains is systematically increased. We find that these interactions between the side chains can induce (for the nine-mer almost completely) a transition from a coil to a helical state. This transition is found to be characterized by three states in which the intermediate state is a partially folded α-helical conformation. In the absence of any interactions between the side chains the free energy change for helix formation has a small positive value indicating that favorable contributions from the side chains are necessary to stabilize the helical conformation. Thus, the helix-coil transition is controlled by the effective potentials between the side-chain residues and the magnitude of the required attraction per residue, which is on the order of the thermal energy, reduces with the length of the peptide. Surprisingly, the plots of the population of the helical state (or the change in the free energy for helix formation) as a function of the total effective interactions between the side chains in the helical state for all peptide lengths fall on the same curve.

Conditional Solvation Thermodynamics of Isoleucine in Model Peptides and the Limitations of the Group-Transfer Model

PubMed Central

2015-01-01

The hydration thermodynamics of the amino acid X relative to the reference G (glycine) or the hydration thermodynamics of a small-molecule analog of the side chain of X is often used to model the contribution of X to protein stability and solution thermodynamics. We consider the reasons for successes and limitations of this approach by calculating and comparing the conditional excess free energy, enthalpy, and entropy of hydration of the isoleucine side chain in zwitterionic isoleucine, in extended penta-peptides, and in helical deca-peptides. Butane in gauche conformation serves as a small-molecule analog for the isoleucine side chain. Parsing the hydrophobic and hydrophilic contributions to hydration for the side chain shows that both of these aspects of hydration are context-sensitive. Furthermore, analyzing the solute–solvent interaction contribution to the conditional excess enthalpy of the side chain shows that what is nominally considered a property of the side chain includes entirely nonobvious contributions of the background. The context-sensitivity of hydrophobic and hydrophilic hydration and the conflation of background contributions with energetics attributed to the side chain limit the ability of a single scaling factor, such as the fractional solvent exposure of the group in the protein, to map the component energetic contributions of the model-compound data to their value in the protein. But ignoring the origin of cancellations in the underlying components the group-transfer model may appear to provide a reasonable estimate of the free energy for a given error tolerance. PMID:24650057

Synthesis of diketopyrrolopyrrole-based polymers with polydimethylsiloxane side chains and their application in organic field-effect transistors

NASA Astrophysics Data System (ADS)

Ohnishi, Inori; Hashimoto, Kazuhito; Tajima, Keisuke

2018-03-01

Linear polydimethylsiloxane (PDMS) was investigated as a solubilizing group for π-conjugated polymers with the aim of combining high solubility in organic solvents with the molecular packing in solid films that is advantageous for charge transport. Diketopyrrolopyrrole-based copolymers with different contents and substitution patterns of the PDMS side chains were synthesized and evaluated for application in organic field-effect transistors. The PDMS side chains greatly increased the solubility of the polymers and led to shorter d-spacings of the π-stacking in the thin films compared with polymers containing conventional branched alkyl side chains.

The Role of the Side Chain on the Performance of N-type Conjugated Polymers in Aqueous Electrolytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giovannitti, Alexander; Maria, Iuliana P.; Hanifi, David

Here, we report a design strategy that allows the preparation of solution processable n-type materials from low boiling point solvents for organic electrochemical transistors (OECTs). The polymer backbone is based on NDI-T2 copolymers where a branched alkyl side chain is gradually exchanged for a linear ethylene glycol-based side chain. A series of random copolymers was prepared with glycol side chain percentages of 0, 10, 25, 50, 75, 90, and 100 with respect to the alkyl side chains. These were characterized to study the influence of the polar side chains on interaction with aqueous electrolytes, their electrochemical redox reactions, and performancemore » in OECTs when operated in aqueous electrolytes. We observed that glycol side chain percentages of >50% are required to achieve volumetric charging, while lower glycol chain percentages show a mixed operation with high required voltages to allow for bulk charging of the organic semiconductor. A strong dependence of the electron mobility on the fraction of glycol chains was found for copolymers based on NDI-T2, with a significant drop as alkyl side chains are replaced by glycol side chains.« less

The Role of the Side Chain on the Performance of N-type Conjugated Polymers in Aqueous Electrolytes.

PubMed

Giovannitti, Alexander; Maria, Iuliana P; Hanifi, David; Donahue, Mary J; Bryant, Daniel; Barth, Katrina J; Makdah, Beatrice E; Savva, Achilleas; Moia, Davide; Zetek, Matyáš; Barnes, Piers R F; Reid, Obadiah G; Inal, Sahika; Rumbles, Garry; Malliaras, George G; Nelson, Jenny; Rivnay, Jonathan; McCulloch, Iain

2018-05-08

We report a design strategy that allows the preparation of solution processable n-type materials from low boiling point solvents for organic electrochemical transistors (OECTs). The polymer backbone is based on NDI-T2 copolymers where a branched alkyl side chain is gradually exchanged for a linear ethylene glycol-based side chain. A series of random copolymers was prepared with glycol side chain percentages of 0, 10, 25, 50, 75, 90, and 100 with respect to the alkyl side chains. These were characterized to study the influence of the polar side chains on interaction with aqueous electrolytes, their electrochemical redox reactions, and performance in OECTs when operated in aqueous electrolytes. We observed that glycol side chain percentages of >50% are required to achieve volumetric charging, while lower glycol chain percentages show a mixed operation with high required voltages to allow for bulk charging of the organic semiconductor. A strong dependence of the electron mobility on the fraction of glycol chains was found for copolymers based on NDI-T2, with a significant drop as alkyl side chains are replaced by glycol side chains.

The Role of the Side Chain on the Performance of N-type Conjugated Polymers in Aqueous Electrolytes

DOE PAGES

Giovannitti, Alexander; Maria, Iuliana P.; Hanifi, David; ...

2018-04-24

Here, we report a design strategy that allows the preparation of solution processable n-type materials from low boiling point solvents for organic electrochemical transistors (OECTs). The polymer backbone is based on NDI-T2 copolymers where a branched alkyl side chain is gradually exchanged for a linear ethylene glycol-based side chain. A series of random copolymers was prepared with glycol side chain percentages of 0, 10, 25, 50, 75, 90, and 100 with respect to the alkyl side chains. These were characterized to study the influence of the polar side chains on interaction with aqueous electrolytes, their electrochemical redox reactions, and performancemore » in OECTs when operated in aqueous electrolytes. We observed that glycol side chain percentages of >50% are required to achieve volumetric charging, while lower glycol chain percentages show a mixed operation with high required voltages to allow for bulk charging of the organic semiconductor. A strong dependence of the electron mobility on the fraction of glycol chains was found for copolymers based on NDI-T2, with a significant drop as alkyl side chains are replaced by glycol side chains.« less

Aqueous Processing for Printed Organic Electronics: Conjugated Polymers with Multistage Cleavable Side Chains

PubMed Central

2017-01-01

The ability to process conjugated polymers via aqueous solution is highly advantageous for reducing the costs and environmental hazards of large scale roll-to-roll processing of organic electronics. However, maintaining competitive electronic properties while achieving aqueous solubility is difficult for several reasons: (1) Materials with polar functional groups that provide aqueous solubility can be difficult to purify and characterize, (2) many traditional coupling and polymerization reactions cannot be performed in aqueous solution, and (3) ionic groups, though useful for obtaining aqueous solubility, can lead to a loss of solid-state order, as well as a screening of any applied bias. As an alternative, we report a multistage cleavable side chain method that combines desirable aqueous processing attributes without sacrificing semiconducting capabilities. Through the attachment of cleavable side chains, conjugated polymers have for the first time been synthesized, characterized, and purified in organic solvents, converted to a water-soluble form for aqueous processing, and brought through a final treatment to cleave the polymer side chains and leave behind the desired electronic material as a solvent-resistant film. Specifically, we demonstrate an organic soluble polythiophene that is converted to an aqueous soluble polyelectrolyte via hydrolysis. After blade coating from an aqueous solution, UV irradiation is used to cleave the polymer’s side chains, resulting in a solvent-resistant, electroactive polymer thin film. In application, this process results in aqueous printed materials with utility for solid-state charge transport in organic field effect transistors (OFETs), along with red to colorless electrochromism in ionic media for color changing displays, demonstrating its potential as a universal method for aqueous printing in organic electronics. PMID:28979937

Aqueous Processing for Printed Organic Electronics: Conjugated Polymers with Multistage Cleavable Side Chains.

PubMed

Schmatz, Brian; Yuan, Zhibo; Lang, Augustus W; Hernandez, Jeff L; Reichmanis, Elsa; Reynolds, John R

2017-09-27

The ability to process conjugated polymers via aqueous solution is highly advantageous for reducing the costs and environmental hazards of large scale roll-to-roll processing of organic electronics. However, maintaining competitive electronic properties while achieving aqueous solubility is difficult for several reasons: (1) Materials with polar functional groups that provide aqueous solubility can be difficult to purify and characterize, (2) many traditional coupling and polymerization reactions cannot be performed in aqueous solution, and (3) ionic groups, though useful for obtaining aqueous solubility, can lead to a loss of solid-state order, as well as a screening of any applied bias. As an alternative, we report a multistage cleavable side chain method that combines desirable aqueous processing attributes without sacrificing semiconducting capabilities. Through the attachment of cleavable side chains, conjugated polymers have for the first time been synthesized, characterized, and purified in organic solvents, converted to a water-soluble form for aqueous processing, and brought through a final treatment to cleave the polymer side chains and leave behind the desired electronic material as a solvent-resistant film. Specifically, we demonstrate an organic soluble polythiophene that is converted to an aqueous soluble polyelectrolyte via hydrolysis. After blade coating from an aqueous solution, UV irradiation is used to cleave the polymer's side chains, resulting in a solvent-resistant, electroactive polymer thin film. In application, this process results in aqueous printed materials with utility for solid-state charge transport in organic field effect transistors (OFETs), along with red to colorless electrochromism in ionic media for color changing displays, demonstrating its potential as a universal method for aqueous printing in organic electronics.

Tension Amplification in Molecular Brushes in Solutions and on Substrates

PubMed Central

Panyukov, Sergey; Zhulina, Ekaterina B.; Sheiko, Sergei S.; Randall, Greg C.; Brock, James; Rubinstein, Michael

2009-01-01

Molecular bottle-brushes are highly branched macromolecules with side chains densely grafted to a long polymer backbone. The brush-like architecture allows focusing of the side-chain tension to the backbone and its amplification from the picoNewton to nanoNewton range. The backbone tension depends on the overall molecular conformation and the surrounding environment. Here we study the relation between the tension and conformation of the molecular brushes in solutions, melts, and on substrates. In solutions, we find that the backbone tension in dense brushes with side chains attached to every backbone monomer is on the order of f0N3/8 in athermal solvents, f0N1/3 in θ-solvents, and f0 in poor solvents and melts, where N is the degree of polymerization of side chains, f0≃ kBT/b is the maximum tension in side chains, b is the Kuhn length, kB is Boltzmann constant, and T is absolute temperature. Depending on the side chain length and solvent quality, molecular brushes in solutions develop tension on the order of 10–100 picoNewtons, which is sufficient to break hydrogen bonds. Significant amplification of tension occurs upon adsorption of brushes onto a substrate. On a strongly attractive substrate, maximum tension in the brush backbone is ~ f0N, reaching values on the order of several nanoNewtons which exceed the strength of a typical covalent bond. At low grafting density and high spreading parameter the cross-sectional profile of adsorbed molecular brush is approximately rectangular with thicknes ~bA/S, where A is the Hamaker constant and S is the spreading parameter. At a very high spreading parameter (S > A), the brush thickness saturates at monolayer ~ b. At a low spreading parameter, the cross-sectional profile of adsorbed molecular brush has triangular tent-like shape. In the cross-over between these two opposite cases, covering a wide range of parameter space, the adsorbed molecular brush consists of two layers. Side chains in the lower layer gain surface energy due to the direct interaction with the substrate, while the second layer spreads on the top of the first layer. Scaling theory predicts that this second layer has a triangular cross-section with width R ~ N3/5 and height h ~ N2/5. Using self-consistent field theory we calculate the cap profile y (x) = h (1 − x2/R2)2, where x is the transverse distance from the backbone. The predicted cap shape is in excellent agreement with both computer simulation and experiment. PMID:19673133

Fast internal dynamics in alcohol dehydrogenase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monkenbusch, M.; Stadler, A., E-mail: a.stadler@fz-juelich.de; Biehl, R.

2015-08-21

Large-scale domain motions in alcohol dehydrogenase (ADH) have been observed previously by neutron spin-echo spectroscopy (NSE). We have extended the investigation on the dynamics of ADH in solution by using high-resolution neutron time-of-flight (TOF) and neutron backscattering (BS) spectroscopy in the incoherent scattering range. The observed hydrogen dynamics were interpreted in terms of three mobility classes, which allowed a simultaneous description of the measured TOF and BS spectra. In addition to the slow global protein diffusion and domain motions observed by NSE, a fast internal process could be identified. Around one third of the protons in ADH participate in themore » fast localized diffusive motion. The diffusion coefficient of the fast internal motions is around two third of the value of the surrounding D{sub 2}O solvent. It is tempting to associate the fast internal process with solvent exposed amino acid residues with dangling side chains.« less

Cooperative Order-Disorder Transition of Carboxylated Schizophyllan in Water-Dimethylsulfoxide Mixtures.

PubMed

Yoshiba, Kazuto; Dobashi, Toshiaki; Ulset, Ann-Sissel T; Christensen, Bjørn E

2018-06-18

Carboxylated schizophyllan ("sclerox") is a chemically modified polysaccharide obtained by partial periodate oxidation and subsequent chlorite oxidation of schizophyllan, a water-soluble neutral polysaccharide having a β-1,3-linked glucan backbone and a β-1,6-linked d-glucose residue side chain at every third residue of the main chain. The triple helix of schizophyllan in water has a cooperative order-disorder transition associated with the side chains. The transition is strongly affected by the presence (mole fraction) of dimethylsulfoxide (DMSO). In the present study, the solvent effects on the order-disorder transition of sclerox with different degrees of carboxylation (DS) in water-DMSO mixtures were investigated with differential scanning calorimetry and optical rotation. The transition temperature ( T r ) and transition enthalpy (Δ H r ) strongly depended on the mole fraction of DMSO ( x D ). Data were further analyzed with the statistical theory for the linear cooperative transition, taking into account the solvent effect, where DMSO molecules are selectively associated with the unmodified side chains. The modified side chain does not contribute to the transition; hence, Δ H r decreases with increasing DS. The dependence of T r on the DMSO content becomes weaker than that for unmodified schizophyllan. The theoretical analyses indicated that the number of sites binding with the DMSO molecule and the successive ordered sequence of the ordered unit of the triple helix are changed by carboxylation.

Highly crystalline films of PCPDTBT with branched side chains by solvent vapor crystallization: influence on opto-electronic properties.

PubMed

Fischer, Florian S U; Trefz, Daniel; Back, Justus; Kayunkid, Navaphun; Tornow, Benjamin; Albrecht, Steve; Yager, Kevin G; Singh, Gurpreet; Karim, Alamgir; Neher, Dieter; Brinkmann, Martin; Ludwigs, Sabine

2015-02-18

PCPDTBT, a marginally crystallizable polymer, is crystallized into a new crystal structure using solvent-vapor annealing. Highly ordered areas with three different polymer-chain orientations are identified using TEM/ED, GIWAXS, and polarized Raman spectroscopy. The optical and structural properties differ significantly from films prepared by standard device preparation protocols. Bilayer solar cells, however, show similar performance. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Origins of the helical wrapping of phenyleneethynylene polymers about single-walled carbon nanotubes.

PubMed

Von Bargen, Christopher D; MacDermaid, Christopher M; Lee, One-Sun; Deria, Pravas; Therien, Michael J; Saven, Jeffery G

2013-10-24

The highly charged, conjugated polymer poly[p-{2,5-bis(3-propoxysulfonicacidsodiumsalt)}phenylene]ethynylene (PPES) has been shown to wrap single-wall carbon nanotubes (SWNTs), adopting a robust helical superstructure. Surprisingly, PPES adopts a helical rather than a linear conformation when adhered to SWNTs. The complexes formed by PPES and related polymers upon helical wrapping of a SWNT are investigated using atomistic molecular dynamics (MD) simulations in the presence and absence of aqueous solvent. In simulations of the PPES/SWNT system in an aqueous environment, PPES spontaneously takes on a helical conformation. A potential of mean force, ΔA(ξ), is calculated as a function of ξ, the component of the end-to-end vector of the polymer chain projected on the SWNT axis; ξ is a monotonic function of the polymer's helical pitch. ΔA(ξ) provides a means to quantify the relative free energies of helical conformations of the polymer when wrapped about the SWNT. The aqueous system possesses a global minimum in ΔA(ξ) at the experimentally observed value of the helical pitch. The presence of this minimum is associated with preferred side chain conformations, where the side chains adopt conformations that provide van der Waals contact between the tubes and the aliphatic components of the side chains, while exposing the anionic sulfonates for aqueous solvation. The simulations provide a free energy estimate of a 0.2 kcal/mol/monomer preference for the helical over the linear conformation of the PPES/SWNT system in an aqueous environment.

Unifying the microscopic picture of His-containing turns: from gas phase model peptides to crystallized proteins.

PubMed

Sohn, Woon Yong; Habka, Sana; Gloaguen, Eric; Mons, Michel

2017-07-14

The presence in crystallized proteins of a local anchoring between the side chain of a His residue, located in the central position of a γ- or β-turn, and its local main chain environment, was assessed by the comparison of protein structures with relevant isolated model peptides. Gas phase laser spectroscopy, combined with relevant quantum chemistry methods, was used to characterize the γ- and β-turn structures in these model peptides. A conformer-selective NH stretch infrared study provided evidence for the formation in vacuo of two types of short-range H-bonded motifs, labelled ε-6 δ and δ- δ 7/π H , bridging the His side chain (in its gauche+ rotamer) to the neighbouring NH(i) and CO(i) sites of the backbone; each side chain-backbone motif was found to be specific of the tautomer (ε or δ) adopted by the His side chain in its neutral form. A close comparison between β- and γ-turns, selected from the Protein Data Bank, and the gas phase models demonstrated that a significant proportion of the gauche+ His rotamer distribution of proteins was well described by the corresponding gas phase H-bonded structures. This is consistent with the persistence of local 6 δ and δ 7/π H intramolecular interactions in proteins, emphasizing the relevance of gas phase data to secondary structures that are poorly accessible to solvents, e.g., in the case of a specific compact topology (Xxx-His β-turns). Deviations from the gas phase structures were also observed, mainly in His-Xxx β-turns, and assigned to solvent accessible turn structures. They were well accounted for by theoretical models of microhydrated turns, in which a few solvent molecules take over the gas phase motifs, constituting a water-mediated local anchoring of the His side chain to the backbone. Finally, the present gas phase benchmark models also pinpointed weaknesses in the protein structure determination by X-ray diffraction analysis; in particular, besides the lack of tautomer information, inaccuracies in the description of imidazole ring flip rotamerism were identified.

Localized conformational interrogation of antibody and antibody-drug conjugates by site-specific carboxyl group footprinting.

PubMed

Pan, Lucy Yan; Salas-Solano, Oscar; Valliere-Douglass, John F

Establishing and maintaining conformational integrity of monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) during development and manufacturing is critical for ensuring their clinical efficacy. As presented here, we applied site-specific carboxyl group footprinting (CGF) for localized conformational interrogation of mAbs. The approach relies on covalent labeling that introduces glycine ethyl ester tags onto solvent-accessible side chains of protein carboxylates. Peptide mapping is used to monitor the labeling kinetics of carboxyl residues and the labeling kinetics reflects the conformation or solvent-accessibility of side chains. Our results for two case studies are shown here. The first study was aimed at defining the conformational changes of mAbs induced by deglycosylation. We found that two residues in C H 2 domain (D268 and E297) show significantly enhanced side chain accessibility upon deglycosylation. This site-specific result highlighted the advantage of monitoring the labeling kinetics at the amino acid level as opposed to the peptide level, which would result in averaging out of highly localized conformational differences. The second study was designed to assess conformational effects brought on by conjugation of mAbs with drug-linkers. All 59 monitored carboxyl residues displayed similar solvent-accessibility between the ADC and mAb under native conditions, which suggests the ADC and mAb share similar side chain conformation. The findings are well correlated and complementary with results from other assays. This work illustrated that site-specific CGF is capable of pinpointing local conformational changes in mAbs or ADCs that might arise during development and manufacturing. The methodology can be readily implemented within the industry to provide comprehensive conformational assessment of these molecules.

Dual-component system dimethyl sulfoxide/LiCl as a solvent and catalyst for homogeneous ring-opening grafted polymerization of ε-caprolactone onto xylan.

PubMed

Zhang, Xue-Qin; Chen, Ming-Jie; Liu, Chuan-Fu; Sun, Run-Cang

2014-01-22

The preparation of xylan-graft-poly(ε-caprolactone) (xylan-g-PCL) copolymers was investigated by homogeneous ring-opening polymerization (ROP) in a dual-component system containing Lewis base LiCl and strong polar aprotic solvent dimethyl sulfoxide (DMSO). DMSO/LiCl acted as solvent, base, and catalyst for the ROP reaction. The effects of the parameters, including the reaction temperature, molar ratio of ε-caprolactone (ε-CL) to anhydroxylose units (AXU) in xylan, and reaction time, on the degree of substitution (DS) and weight percent of PCL side chain (WPCL) were investigated. The results showed that xylan-g-PCL copolymers with low DS in the range of 0.03-0.39 were obtained under the given conditions. The Fourier transform infrared spectroscopy (FTIR), (1)H nuclear magnetic resonance (NMR), (13)C NMR, (1)H-(1)H correlation spectroscopy (COSY), and (1)H-(13)C correlation two-dimensional (2D) NMR [heteronuclear single-quantum coherence (HSQC)] characterization provided more evidence of the attachment of side chains onto xylan. Only one ε-CL was confirmed to be attached onto xylan with each side chain. Integration of resonances assigned to the substituted C2 and C3 in the HSQC spectrum also indicated 69.23 and 30.77% of PCL side chains attached to AXU at C3 and C2 positions, respectively. Although the attachment of PCL onto xylan led to the decreased thermal stability of xylan, the loss of unrecovered xylan fractions with low molecular weight because of the high solubility of xylan in DMSO/LiCl resulted in the increased thermal stability of the samples. This kind of xylan derivative has potential application in environmentally friendly and biodegradable materials considering the good biodegradability of xylan and PCL.

Protein side chain conformation predictions with an MMGBSA energy function.

PubMed

Gaillard, Thomas; Panel, Nicolas; Simonson, Thomas

2016-06-01

The prediction of protein side chain conformations from backbone coordinates is an important task in structural biology, with applications in structure prediction and protein design. It is a difficult problem due to its combinatorial nature. We study the performance of an "MMGBSA" energy function, implemented in our protein design program Proteus, which combines molecular mechanics terms, a Generalized Born and Surface Area (GBSA) solvent model, with approximations that make the model pairwise additive. Proteus is not a competitor to specialized side chain prediction programs due to its cost, but it allows protein design applications, where side chain prediction is an important step and MMGBSA an effective energy model. We predict the side chain conformations for 18 proteins. The side chains are first predicted individually, with the rest of the protein in its crystallographic conformation. Next, all side chains are predicted together. The contributions of individual energy terms are evaluated and various parameterizations are compared. We find that the GB and SA terms, with an appropriate choice of the dielectric constant and surface energy coefficients, are beneficial for single side chain predictions. For the prediction of all side chains, however, errors due to the pairwise additive approximation overcome the improvement brought by these terms. We also show the crucial contribution of side chain minimization to alleviate the rigid rotamer approximation. Even without GB and SA terms, we obtain accuracies comparable to SCWRL4, a specialized side chain prediction program. In particular, we obtain a better RMSD than SCWRL4 for core residues (at a higher cost), despite our simpler rotamer library. Proteins 2016; 84:803-819. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Theoretical Studies of Interactions between O-Phosphorylated and Standard Amino-Acid Side-Chain Models in Water

PubMed Central

Wiśniewska, Marta; Sobolewski, Emil; Ołdziej, Stanisław; Liwo, Adam; Scheraga, Harold A.; Makowski, Mariusz

2015-01-01

Phosphorylation is a common post-translational modification of the amino-acid side chains (serine, tyrosine, and threonine) that contain hydroxyl groups. The transfer of the negatively charged phosphate group from an ATP molecule to such amino-acid side chains leads to changes in the local conformations of proteins and the pattern of interactions with other amino-acid side-chains. A convenient characteristic of the side chain–side chain interactions in the context of an aqueous environment is the potential of mean force (PMF) in water. A series of umbrella-sampling molecular dynamic (MD) simulations with the AMBER force field were carried out for pairs of O-phosphorylated serine (pSer), threonine (pThr), and tyrosine, (pTyr) with natural amino acids in a TIP3P water model as a solvent at 298 K. The weighted-histogram analysis method was used to calculate the four-dimensional potentials of mean force. The results demonstrate that the positions and depths of the contact minima and the positions and heights of the desolvation maxima, including their dependence on the relative orientation depend on the character of the interacting pairs. More distinct minima are observed for oppositely charged pairs such as, e.g., O-phosphorylated side-chains and positively charged ones, such as the side-chains of lysine and arginine. PMID:26100791

Synthesis, surface characterization, and biointeraction studies of low-surface energy side-chain polyetherurethanes

NASA Astrophysics Data System (ADS)

Porter, Stephen Christopher

1999-10-01

New segmented polyetherurethanes (PEUs) with low surface energy hydrocarbon and fluorocarbon side-chains attached to the polymer hard segments were synthesized. The surface chemistry of solvent cast polymer films was studied using X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and dynamic contact angle (DCA) measurements. Increases in the overall density and length of the alkyl side-chains within the PEUs resulted in greater side-chain concentrations at the polymer surface. PEUs bearing long alkyl (> C10 ) and perfluorocarbon side-chains were found to posses surfaces with highly enriched side-chain concentrations relative to the bulk polymer. In PEUs with significant side-chain surface enrichment, the relatively polar hard segment blocks were shown to reside in high concentrations just below the side-chain enriched surface layer. Furthermore, DCA measurements demonstrated that the surface of the alkyl side-chain PEUs did not undergo significant rearrangement when placed into an aqueous environment, whereas the surface of a hard segment model polymer bearing C18 sidechains (PEU-C18-HS) did. Hydrogen bonding within the PEUs was examined using FTIR and was shown to be disrupted by the addition of side-chains; an effect dependent on the density but not on the length of the side-chains. Heteropolymer blends comprised of mixtures of high side-chain density and side-chain free PEUs were compared with homopolymers having the same overall side-chain concentration as the blends. Significantly more surface enrichment of side-chains was found in the heteropolymer blends whereas hydrogen bonding nearly the same as in the homopolymers. Adsorption of native and delipidized human serum albumin (HSA) from pure solution and blood plasma; the elutabilty of adsorbed HSA; and static platelet adhesion to plasma preadsorbed surfaces, were all examined on alkyl side-chain PEUs. Several polymers with high C18 side-chain densities displayed increased affinity for albumin, and reduced elutability. Among these, PEU-C18-HS demonstrated a significant reduction in platelet adhesion at low plasma pre-adsorption concentrations. However, competitive binary adsorption of fibrinogen in the presence of HSA demonstrated lower relative albumin affinity for PEU-C18-HS than other PEUs. The observed effects are thought to be mainly a result of increased surface hydrophobicity of the alkyl-side chain modified PEU, and not high specificity albumin binding.

Use of side-chain for rational design of n-type diketopyrrolopyrrole-based conjugated polymers: what did we find out?

PubMed

Kanimozhi, Catherine; Yaacobi-Gross, Nir; Burnett, Edmund K; Briseno, Alejandro L; Anthopoulos, Thomas D; Salzner, Ulrike; Patil, Satish

2014-08-28

The primary role of substituted side chains in organic semiconductors is to increase their solubility in common organic solvents. In the recent past, many literature reports have suggested that the side chains play a critical role in molecular packing and strongly impact the charge transport properties of conjugated polymers. In this work, we have investigated the influence of side-chains on the charge transport behavior of a novel class of diketopyrrolopyrrole (DPP) based alternating copolymers. To investigate the role of side-chains, we prepared four diketopyrrolopyrrole-diketopyrrolopyrrole (DPP-DPP) conjugated polymers with varied side-chains and carried out a systematic study of thin film microstructure and charge transport properties in polymer thin-film transistors (PTFTs). Combining results obtained from grazing incidence X-ray diffraction (GIXD) and charge transport properties in PTFTs, we conclude side-chains have a strong influence on molecular packing, thin film microstructure, and the charge carrier mobility of DPP-DPP copolymers. However, the influence of side-chains on optical properties was moderate. The preferential "edge-on" packing and dominant n-channel behavior with exceptionally high field-effect electron mobility values of >1 cm(2) V(-1) s(-1) were observed by incorporating hydrophilic (triethylene glycol) and hydrophobic side-chains of alternate DPP units. In contrast, moderate electron and hole mobilities were observed by incorporation of branched hydrophobic side-chains. This work clearly demonstrates that the subtle balance between hydrophobicity and hydrophilicity induced by side-chains is a powerful strategy to alter the molecular packing and improve the ambipolar charge transport properties in DPP-DPP based conjugated polymers. Theoretical analysis supports the conclusion that the side-chains influence polymer properties through morphology changes, as there is no effect on the electronic properties in the gas phase. The exceptional electron mobility is at least partially a result of the strong intramolecular conjugation of the donor and acceptor as evidenced by the unusually wide conduction band of the polymer.

Rapid assessment of oxidation via middle-down LCMS correlates with methionine side-chain solvent-accessible surface area for 121 clinical stage monoclonal antibodies.

PubMed

Yang, Rong; Jain, Tushar; Lynaugh, Heather; Nobrega, R Paul; Lu, Xiaojun; Boland, Todd; Burnina, Irina; Sun, Tingwan; Caffry, Isabelle; Brown, Michael; Zhi, Xiaoyong; Lilov, Asparouh; Xu, Yingda

Susceptibility of methionine to oxidation is an important concern for chemical stability during the development of a monoclonal antibody (mAb) therapeutic. To minimize downstream risks, leading candidates are usually screened under forced oxidation conditions to identify oxidation-labile molecules. Here we report results of forced oxidation on a large set of in-house expressed and purified mAbs with variable region sequences corresponding to 121 clinical stage mAbs. These mAb samples were treated with 0.1% H 2 O 2 for 24 hours before enzymatic cleavage below the hinge, followed by reduction of inter-chain disulfide bonds for the detection of the light chain, Fab portion of heavy chain (Fd) and Fc by liquid chromatography-mass spectrometry. This high-throughput, middle-down approach allows detection of oxidation site(s) at the resolution of 3 distinct segments. The experimental oxidation data correlates well with theoretical predictions based on the solvent-accessible surface area of the methionine side-chains within these segments. These results validate the use of upstream computational modeling to predict mAb oxidation susceptibility at the sequence level.

Sorting of Semiconducting Single-Walled Carbon Nanotubes in Polar Solvents with an Amphiphilic Conjugated Polymer Provides General Guidelines for Enrichment.

PubMed

Ouyang, Jianying; Ding, Jianfu; Lefebvre, Jacques; Li, Zhao; Guo, Chang; Kell, Arnold J; Malenfant, Patrick R L

2018-02-27

Conjugated polymer extraction (CPE) has been shown to be a highly effective method to isolate high-purity semiconducting single-walled carbon nanotubes (sc-SWCNTs). In both literature reports and industrial manufacturing, this method has enabled enrichment of sc-SWCNTs with high purity (≥99.9%). High selectivity is typically obtained in nonpolar aromatic solvents, yet polar solvents may provide process improvements in terms of yield, purity and efficiency. Using an amphiphilic fluorene-alt-pyridine conjugated copolymer with hydrophilic side chains, we have investigated the enrichment of sc-SWCNTs in polar solvents. Various conditions such as polymer/SWCNT ratio, solvent polarity, solvent dielectric constant as well as polymer solubility and SWCNT dispersibility were explored in order to optimize the purity and yield of the enriched product. Herein, we provide insights on CPE by demonstrating that a conjugated polymer having a hydrophobic backbone and hydrophilic oligo(ethylene oxide) side chains provides near full recovery (95%) of sc-SWCNTs using a multiextraction protocol. High purity is also obtained, and differences in chiral selectivity compared to analogous hydrophobic systems were confirmed by optical absorption and Raman spectroscopy as well as photoluminescence excitation mapping. Taking into consideration the solvent dielectric constant, polarity index as well as polymer solubility and SWCNT dispersibility provides a better understanding of structure-property effects on sc-SWCNT enrichment. The resulting hydrophilic SWCNT dispersions demonstrate long-term colloidal stability, making them suitable for ink formulation and high-performance thin-film transistors fabrication.

Single-molecule spectroscopy of the unexpected collapse of an unfolded protein at low pH

NASA Astrophysics Data System (ADS)

Hofmann, Hagen; Nettels, Daniel; Schuler, Benjamin

2013-09-01

The dimensions of intrinsically disordered and unfolded proteins critically depend on the solution conditions, such as temperature, pH, ionic strength, and osmolyte or denarurant concentration. However, a quantitative understanding of how the complex combination of chain-chain and chain-solvent interactions is affected by the solvent is still missing. Here, we take a step towards this goal by investigating the combined effect of pH and denaturants on the dimensions of an unfolded protein. We use single-molecule fluorescence spectroscopy to extract the dimensions of unfolded cold shock protein (CspTm) in mixtures of the denaturants urea and guanidinium chloride (GdmCl) at neutral and acidic pH. Surprisingly, even though a change in pH from 7 to 2.9 increases the net charge of CspTm from -3.8 to +10.2, the radius of gyration of the chain is very similar under both conditions, indicating that protonation of acidic side chains at low pH results in additional hydrophobic interactions. We use a simple shared binding site model that describes the joint effect of urea and GdmCl, together with polyampholyte theory and an ion cloud model that includes the chemical free energy of counterion interactions and side chain protonation, to quantify this effect.

Direct Comparison of Amino Acid and Salt Interactions with Double-Stranded and Single-Stranded DNA from Explicit-Solvent Molecular Dynamics Simulations.

PubMed

Andrews, Casey T; Campbell, Brady A; Elcock, Adrian H

2017-04-11

Given the ubiquitous nature of protein-DNA interactions, it is important to understand the interaction thermodynamics of individual amino acid side chains for DNA. One way to assess these preferences is to perform molecular dynamics (MD) simulations. Here we report MD simulations of 20 amino acid side chain analogs interacting simultaneously with both a 70-base-pair double-stranded DNA and with a 70-nucleotide single-stranded DNA. The relative preferences of the amino acid side chains for dsDNA and ssDNA match well with values deduced from crystallographic analyses of protein-DNA complexes. The estimated apparent free energies of interaction for ssDNA, on the other hand, correlate well with previous simulation values reported for interactions with isolated nucleobases, and with experimental values reported for interactions with guanosine. Comparisons of the interactions with dsDNA and ssDNA indicate that, with the exception of the positively charged side chains, all types of amino acid side chain interact more favorably with ssDNA, with intercalation of aromatic and aliphatic side chains being especially notable. Analysis of the data on a base-by-base basis indicates that positively charged side chains, as well as sodium ions, preferentially bind to cytosine in ssDNA, and that negatively charged side chains, and chloride ions, preferentially bind to guanine in ssDNA. These latter observations provide a novel explanation for the lower salt dependence of DNA duplex stability in GC-rich sequences relative to AT-rich sequences.

Clusters of isoleucine, leucine, and valine side chains define cores of stability in high-energy states of globular proteins: Sequence determinants of structure and stability.

PubMed

Kathuria, Sagar V; Chan, Yvonne H; Nobrega, R Paul; Özen, Ayşegül; Matthews, C Robert

2016-03-01

Measurements of protection against exchange of main chain amide hydrogens (NH) with solvent hydrogens in globular proteins have provided remarkable insights into the structures of rare high-energy states that populate their folding free-energy surfaces. Lacking, however, has been a unifying theory that rationalizes these high-energy states in terms of the structures and sequences of their resident proteins. The Branched Aliphatic Side Chain (BASiC) hypothesis has been developed to explain the observed patterns of protection in a pair of TIM barrel proteins. This hypothesis supposes that the side chains of isoleucine, leucine, and valine (ILV) residues often form large hydrophobic clusters that very effectively impede the penetration of water to their underlying hydrogen bond networks and, thereby, enhance the protection against solvent exchange. The linkage between the secondary and tertiary structures enables these ILV clusters to serve as cores of stability in high-energy partially folded states. Statistically significant correlations between the locations of large ILV clusters in native conformations and strong protection against exchange for a variety of motifs reported in the literature support the generality of the BASiC hypothesis. The results also illustrate the necessity to elaborate this simple hypothesis to account for the roles of adjacent hydrocarbon moieties in defining stability cores of partially folded states along folding reaction coordinates. © 2015 The Protein Society.

Rotational dynamics of coumarin-153 and 4-aminophthalimide in 1-ethyl-3-methylimidazolium alkylsulfate ionic liquids: effect of alkyl chain length on the rotational dynamics.

PubMed

Das, Sudhir Kumar; Sarkar, Moloy

2012-01-12

Rotational dynamics of two neutral organic solutes, coumarin-153 (C-153) and 4-aminophthalimide (AP), with only the latter having hydrogen-bond-donating ability, has been investigated in a series of 1-ethyl-3-methylimidazolium alkyl sulfate ionic liquids as a function of temperature. The ionic liquids differ only in the length of the linear alkyl side chain (alkyl = ethyl, butyl, hexyl, and octyl) on the anionic moiety. The present study has been undertaken to examine the role of alkyl side chains on the rotational dynamics of the two solutes in these ionic liquids. Analysis of the results using Stokes-Einstein-Debye hydrodynamic theory indicates that the rotational dynamics of C-153 lies between the stick and slip boundary condition in the ethyl analogue and finally reaches subslip condition as in case of the octyl substituent. The observed rotational behavior of C-153 has been explained on the basis of an increase in the size of the solvent, which offers lower friction for solute rotation. On the other hand, AP shows superstick behavior in the ethyl system and exceeds the stick limit in the octyl derivative. Superstick behavior of AP has been attributed to the specific hydrogen-bonding interaction between AP and the sulfate moiety. Proton NMR investigation confirms the hydrogen-bonding interaction between the N-H hydrogen of AP and the ionic liquid. The decrease in rotational coupling constant values for AP with increasing length of alkyl side chains has been attributed to the decrease in the solute-solvent-specific interaction with an increase in the alkyl side chain length on the sulfate moiety.

Reorientation Motion and Preferential Interactions of a Peptide in Denaturants and Osmolyte.

PubMed

Jas, Gouri S; Rentchler, Eric C; Słowicka, Agnieszka M; Hermansen, John R; Johnson, Carey K; Middaugh, C Russell; Kuczera, Krzysztof

2016-03-31

Fluorescence anisotropy decay measurements and all atom molecular dynamics simulations are used to characterize the orientational motion and preferential interaction of a peptide, N-acetyl-tryptophan-amide (NATA) containing two peptide bonds, in aqueous, urea, guanidinium chloride (GdmCl), and proline solution. Anisotropy decay measurements as a function of temperature and concentration showed moderate slowing of reorientations in urea and GdmCl and very strong slowing in proline solution, relative to water. These effects deviate significantly from simple proportionality of peptide tumbling time to solvent viscosity, leading to the investigation of microscopic preferential interaction behavior through molecular dynamics simulations. Examination of the interactions of denaturants and osmolyte with the peptide backbone uncovers the presence of strongest interaction with urea, intermediate with proline, and weakest with GdmCl. In contrast, the strongest preferential solvation of the peptide side chain is by the nonpolar part of the proline zwitterion, followed by urea, and GdmCl. Interestingly, the local density of urea around the side chain is higher, but the GdmCl distribution is more organized. Thus, the computed preferential solvation of the side chain by the denaturants and osmolyte can account for the trend in reorientation rates. Analysis of water structure and its dynamics uncovered underlying differences between urea, GdmCl, and proline. Urea exerted the smallest perturbation of water behavior. GdmCl had a larger effect on water, slowing kinetics and stabilizing interactions. Proline had the largest overall interactions, exhibiting a strong stabilizing effect on both water-water and water-peptide hydrogen bonds. The results for this elementary peptide system demonstrate significant differences in microscopic behavior of the examined solvent environments. For the commonly used denaturants, urea tends to form disorganized local aggregates around the peptide groups and has little influence on water, while GdmCl only forms specific interactions with the side chain and tends to destabilize water structure. The protective osmolyte proline has the strongest and most specific interactions with the tryptophan side chain, and also stabilizes both water-water and water-peptide hydrogen bonds. Our results strongly suggest protein or peptide denaturation triggered by urea occurs by direct interaction, whereas GdmCl interacts favorably with side chains and destabilizes peptide-water hydrogen bonds. The stabilization of biopolymers by an osmolyte such as proline is governed by favorable preferential interaction with the side chains and stabilization of water.

Nanoporous poly(3-hexylthiophene) thin film structures from self-organization of a tunable molecular bottlebrush scaffold

DOE PAGES

Ahn, Suk-kyun; Carrillo, Jan-Michael Y.; Keum, Jong K.; ...

2017-04-07

The ability to widely tune the design of macromolecular bottlebrushes provides access to self-assembled nanostructures formed by microphase segregation in melt, thin film and solution that depart from structures adopted by simple linear copolymers. A series of random bottlebrush copolymers containing poly(3-hexylthiophene) (P3HT) and poly(D,L-lactide) (PLA) side chains grafted on a poly(norbornene) backbone were synthesized via ring-opening metathesis polymerization (ROMP) using the grafting through approach. P3HT side chains induce a physical aggregation of the bottlebrush copolymers upon solvent removal by vacuum drying, primarily driven by attractive π–π interactions; however, the amount of aggregation can be controlled by adjusting side chainmore » composition or by adding linear P3HT chains to the bottlebrush copolymers. Coarse-grained molecular dynamics simulations reveal that linear P3HT chains preferentially associate with P3HT side chains of bottlebrush copolymers, which tends to reduce the aggregation. The nanoscale morphology of microphase segregated thin films created by casting P3HT–PLA random bottlebrush copolymers is highly dependent on the composition of P3HT and PLA side chains, while domain spacing of nanostructures is mainly determined by the length of the side chains. The selective removal of PLA side chains under alkaline conditions generates nanoporous P3HT structures that can be tuned by manipulating molecular design of the bottlebrush scaffold, which is affected by molecular weight and grafting density of the side chains, and their sequence. Furthermore, the ability to exploit the unusual architecture of bottlebrushes to fabricate tunable nanoporous P3HT thin film structures may be a useful way to design templates for optoelectronic applications or membranes for separations.« less

Nanoporous poly(3-hexylthiophene) thin film structures from self-organization of a tunable molecular bottlebrush scaffold

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahn, Suk-kyun; Carrillo, Jan-Michael Y.; Keum, Jong K.

The ability to widely tune the design of macromolecular bottlebrushes provides access to self-assembled nanostructures formed by microphase segregation in melt, thin film and solution that depart from structures adopted by simple linear copolymers. A series of random bottlebrush copolymers containing poly(3-hexylthiophene) (P3HT) and poly(D,L-lactide) (PLA) side chains grafted on a poly(norbornene) backbone were synthesized via ring-opening metathesis polymerization (ROMP) using the grafting through approach. P3HT side chains induce a physical aggregation of the bottlebrush copolymers upon solvent removal by vacuum drying, primarily driven by attractive π–π interactions; however, the amount of aggregation can be controlled by adjusting side chainmore » composition or by adding linear P3HT chains to the bottlebrush copolymers. Coarse-grained molecular dynamics simulations reveal that linear P3HT chains preferentially associate with P3HT side chains of bottlebrush copolymers, which tends to reduce the aggregation. The nanoscale morphology of microphase segregated thin films created by casting P3HT–PLA random bottlebrush copolymers is highly dependent on the composition of P3HT and PLA side chains, while domain spacing of nanostructures is mainly determined by the length of the side chains. The selective removal of PLA side chains under alkaline conditions generates nanoporous P3HT structures that can be tuned by manipulating molecular design of the bottlebrush scaffold, which is affected by molecular weight and grafting density of the side chains, and their sequence. Furthermore, the ability to exploit the unusual architecture of bottlebrushes to fabricate tunable nanoporous P3HT thin film structures may be a useful way to design templates for optoelectronic applications or membranes for separations.« less

The effects of side-chain-induced disorder on the emission spectra and quantum yields of oligothiophene nano-aggregates. A combined experimental and MD-TDDFT study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Jiyun; Jeon, SuKyung; Kim, Janice J.

2014-07-24

Oligomeric thiophenes are commonly-used components in organic electronics and solar cells. These molecules stack and/or aggregate readily under the processing conditions used to form thin films for these applications, significantly altering their optical and charge-transport properties. To determine how these effects depend on the substitution pattern of the thiophene main chains, nano-aggregates of three sexi-thiophene (6T) oligomers having different alkyl substitution patterns were formed using solvent poisoning techniques and studied using steady-state and time-resolved emission spectroscopy. The results indicate the substantial role played by the side-chain substituents in determining the emissive properties of these species. Both the measured spectral changesmore » and their dependence on substitution are well modeled by combined quantum chemistry and molecular dynamics simulations. The simulations connect the side-chain-induced disorder, which determines the favorable chain packing configurations within the aggregates, with their measured electronic spectra.« less

A specific transition state for S-peptide combining with folded S-protein and then refolding

PubMed Central

Goldberg, Jonathan M.; Baldwin, Robert L.

1999-01-01

We measured the folding and unfolding kinetics of mutants for a simple protein folding reaction to characterize the structure of the transition state. Fluorescently labeled S-peptide analogues combine with S-protein to form ribonuclease S analogues: initially, S-peptide is disordered whereas S-protein is folded. The fluorescent probe provides a convenient spectroscopic probe for the reaction. The association rate constant, kon, and the dissociation rate constant, koff, were both determined for two sets of mutants. The dissociation rate constant is measured by adding an excess of unlabeled S-peptide analogue to a labeled complex (RNaseS*). This strategy allows kon and koff to be measured under identical conditions so that microscopic reversibility applies and the transition state is the same for unfolding and refolding. The first set of mutants tests the role of the α-helix in the transition state. Solvent-exposed residues Ala-6 and Gln-11 in the α-helix of native RNaseS were replaced by the helix destabilizing residues glycine or proline. A plot of log kon vs. log Kd for this series of mutants is linear over a very wide range, with a slope of −0.3, indicating that almost all of the molecules fold via a transition state involving the helix. A second set of mutants tests the role of side chains in the transition state. Three side chains were investigated: Phe-8, His-12, and Met-13, which are known to be important for binding S-peptide to S-protein and which also contribute strongly to the stability of RNaseS*. Only the side chain of Phe-8 contributes significantly, however, to the stability of the transition state. The results provide a remarkably clear description of a folding transition state. PMID:10051587

Structural changes of cytochrome c(552) from Thermus thermophilus adsorbed on anionic and hydrophobic surfaces probed by FTIR and 2D-FTIR spectroscopy.

PubMed

Lecomte, S; Hilleriteau, C; Forgerit, J P; Revault, M; Baron, M H; Hildebrandt, P; Soulimane, T

2001-03-02

The structural changes of cytochrome c(552) bound to anionic and hydrophobic clay surfaces have been investigated by Fourier transform infrared spectroscopy. Binding to the anionic surface of montmorillonite is controlled by electrostatic interactions since addition of electrolyte (0.5 mol L(-1) KCl) causes desorption of more than 2/3 of the protein molecules. Electrostatic binding occurs through the back side of the protein (i.e., remote from the heme site) and is associated only with subtle changes of the secondary structure. In contrast, adsorption to the hydrophobic surface of talc leads to a decrease in alpha-helical structure by ca. 5% and an increase in beta-sheet structure by ca. 6%. These structural changes are attributed to a hydrophobic region on the front surface of cytochrome c(552) close to the partially exposed heme edge. This part on the protein surface is identified as the interaction domain for talc and most likely also serves for binding to the natural reaction partner, a ba(3)-oxidase. Fourier transform infrared spectra of cytochrome c(552) and the clay-cytochrome c(552) complexes have been measured as a function of time following dissolution and suspension in deuterated buffer, respectively. A two-dimensional correlation analysis was applied to these spectra to investigate the dynamics of the structural changes in the protein. For both complexes, adsorption and subsequent unfolding processes in the binding domains are faster than the time resolution of the spectroscopic experiments. Thus, the processes that could be monitored are refolding of peptide segments and side chain rearrangements following the adsorption-induced perturbation of the protein structure and the solvation of the adsorbed protein. In each case, side chain alterations of solvent-exposed tyrosine, aspartate, and glutamate residues were observed. For the cytochrome c(552)-talc complex, these changes are followed by a slow refolding of the peptide chain in the binding domain and, subsequently, a further H/D exchange of amide group protons.

TROSY of side-chain amides in large proteins

PubMed Central

Liu, Aizhuo; Yao, Lishan; Li, Yue; Yan, Honggao

2012-01-01

By using the mixed solvent of 50% H2O/50% D2O and employing deuterium decoupling, TROSY experiments exclusively detect NMR signals from semideuterated isotopomers of carboxamide groups with high sensitivities for proteins with molecular weights up to 80 kDa. This isotopomer-selective strategy extends TROSY experiments from exclusively detecting backbone to both backbone and side-chain amides, particularly in large proteins. Because of differences in both TROSY effect and dynamics between 15N–HE{DZ} and 15N–HZ{DE} isotopomers of the same carboxamide, the 15N transverse magnetization of the latter relaxes significantly faster than that of the former, which provides a direct and reliable stereospecific distinction between the two configurations. The TROSY effects on the 15N–HE{DZ} isotopomers of side-chain amides are as significant as on backbone amides. PMID:17347000

Conformation and hydration of surface grafted and free polyethylene oxide chains in solutions

NASA Astrophysics Data System (ADS)

Dahal, Udaya; Wang, Zilu; Dormidontova, Elena

Due to the wide application of polyethylene oxide (PEO), ranging from biomedicine to fuel cells, it is one of the most studied polymers in the scientific world. In order to elucidate detailed molecular-level insights on the impact of surface grafting on PEO conformation, we performed atomistic molecular dynamics simulations of PEO chains in solution and grafted to a flat gold surface in different solvents. We examined the hydration as well as conformation of the free chain compared to the grafted polymer in pure water and mixed solvents. We find that grafted chains are stiffer and have a stronger tendency to form helical structures in isobutyric acid or mixture of isobutyric acid and water solution than the free chains in corresponding solutions. For grafted chains exposed to pure water the random coil conformation is retained at low grafting density, but becomes stretched and more dehydrated as the grafting density or temperature increases. This research is supported by NSF (DMR-1410928).

Entropy and enthalpy of interaction between amino acid side chains in nanopores

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaitheeswaran, S., E-mail: vaithee05@gmail.com; Thirumalai, D.; Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742

2014-12-14

Understanding the stabilities of proteins in nanopores requires a quantitative description of confinement induced interactions between amino acid side chains. We use molecular dynamics simulations to study the nature of interactions between the side chain pairs ALA-PHE, SER-ASN, and LYS-GLU in bulk water and in water-filled nanopores. The temperature dependence of the bulk solvent potentials of mean force and the interaction free energies in cylindrical and spherical nanopores is used to identify the corresponding entropic and enthalpic components. The entropically stabilized hydrophobic interaction between ALA and PHE in bulk water is enthalpically dominated upon confinement depending on the relative orientationsmore » between the side chains. In the case of SER-ASN, hydrogen bonded configurations that are similar in bulk water are thermodynamically distinct in a cylindrical pore, thus making rotamer distributions different from those in the bulk. Remarkably, salt bridge formation between LYS-GLU is stabilized by entropy in contrast to the bulk. Implications of our findings for confinement-induced alterations in protein stability are briefly outlined.« less

Polyelectrolyte-Surfactant Complexes: A New Class of Organogelators

NASA Astrophysics Data System (ADS)

Cavicchi, Kevin; Liu, Yuqing; Guzman, Gustavo

2011-03-01

Polyelectrolyte-surfactant complexes (PE-SURFs) are a class of polymers generated by neutralizing a polyelectrolyte with an oppositely charged surfactant. It has been found that PE-SURFs composed of polystyrene sulfonate and long chain alkyl dimethyl amines act as good organogelators for a range of hydrophobic, organic solvents. Thermo-reversible organogels are formed by heating and cooling PE-SURF/solvent solutions. The gel transition temperature is influenced by the degree of polymerization, the length of the alkyl side-chain, the solubility parameter of the solvent, and the concentration of the gelator. Freeze-drying and scanning electron microscopy characterization of the resultant xerogels shows the formation of rod- and plate-like network morphologies depending on the system parameters. This behavior is consistent with gelation driven by the self-assembly of the amphiphilic PE-SURFs into micellar networks.

Time-Dependent Solid State Polymorphism of a Series of Donor-Acceptor Dyads

PubMed Central

Peebles, Cameron; Alvey, Paul M.; Lynch, Vincent; Iverson, Brent L.

2014-01-01

In order to exploit the use of favorable electrostatic interactions between aromatic units in directing the assembly of donor-acceptor (D-A) dyads, the present work examines the ability of conjugated aromatic D-A dyads with symmetric side chains to exhibit solid-state polymorphism as a function of time during the solid formation process. Four such dyads were synthesized and their packing in the solid-state from either slower (10-20 days) or faster (1-2 days) evaporation from solvent was investigated using single crystal X-ray analysis and powder X-ray diffraction. Two of the dyads exhibited tail-to-tail (A-A) packing upon slower evaporation from solvent and head-to-tail (D-A) packing upon faster evaporation from solvent. A combination of single crystal analysis and XRD patterns were used to create models wherein a packing model for the other two dyads is proposed. Our findings suggest that while side chain interactions in asymmetric aromatic dyads can play an important role in enforcing segregated D-A dyad assembly, slowly evaporating symmetrically substituted aromatic dyads allows for favorable electrostatic interactions between the aromatic moieties to facilitate the organization of the dyads in the solid-state. PMID:24678269

Conformational study of bovine lactoferricin in membrane-micking conditions by molecular dynamics simulation and circular dichroism.

PubMed

Daidone, Isabella; Magliano, Alessandro; Di Nola, Alfredo; Mignogna, Giuseppina; Clarkson, Matilda Manuela; Lizzi, Anna Rita; Oratore, Arduino; Mazza, Fernando

2011-04-01

Lactoferricins are potent antimicrobial peptides released by pepsin cleavage of Lactoferrins. Bovine Lactoferricin (LfcinB) has higher activity than the intact bovine Lactoferrin, and is the most active among the other Lactoferricins of human, murine and caprine origin. In the intact protein the fragment corresponding to LfcinB is in an helical conformation, while in water LfcinB adopts an amphipathic β-hairpin structure. However, whether any of these structural motifs is the antibacterial active conformation, i.e., the one interacting with bacterial membrane components, remains to be seen. Here we present Circular Dichroism (CD) spectra and Molecular Dynamics (MD) simulations indicating that in membrane-mimicking solvents the LfcinB adopts an amphipathic β-hairpin structure similar to that observed in water, but differing in the dynamic behavior of the side-chains of the two tryptophan residues. In the membrane-mimicking solvent these side-chains show a high propensity to point towards the hydrophobic environment, rather than being in the hydrophobic core as seen in water, while the backbone preserves the hairpin conformation as found in water. These results suggest that the tryptophans might act as anchors pulling the stable, solvent-invariant hairpin structure into the membrane.

What the ultimate polymeric electro-optic materials will be: guest-host, crosslinked, or side-chain?

NASA Astrophysics Data System (ADS)

Zhang, Cheng; Zhang, Hua; Oh, Min-Cheol; Dalton, Larry R.; Steier, William H.

2003-07-01

Material processing and device fabrication of many different electro-optic (EO) polymers developed at USC are reviewed. Detailed discussion is given to guest-host CLD/APCs, crosslinking perfluorocyclobutane (PFCB) polymer CX1, and thermally stable side-chain polymers CX2 and CX3. Excellent EO performance (1.4V at 1.31 μm, 2.1 V at 1.55 μm) was achieved in CLD/APC Mach-Zehnder modulators (2-cm, push-pull). CLD/APCs also possess low optical losses (1.2 dB/cm in slab waveguides and in thick core channel waveguides). However, the guest-host materials only have limited thermal stability (110-132 °C in short term, <60 °C in long term) and require special techniques in device fabrication. The crosslinking polymer CX1 was able to provide long-term stability at 85 oC when fully cured. It also has a low optical loss (comparable to CLD/APCs) before curing and decent EO coefficient when poled at 180 °C. However, after the films were poled at the crosslinking temperatures (200 °C or above), the transmissions of the waveguides and EO activity became very poor due to poling-induced chromophore degradation. By judicial molecular design of both chromophore and monomer structures to suppress thermal motion of polymer segments, we were able to realize the same or even better thermal stability in side-chain polymers CX2 and CX3. Since no curing is needed, devices can be poled at their optimal poling temperatures, and all good properties can be obtained simultaneously. Despite the excellent solubility in chlorinated solvents, these side-chain polymers are resistant to some other organic solvents or solutions such as acetone, photoresist and various UV-curable liquids.

Acidic-basic properties of three alanine-based peptides containing acidic and basic side chains: comparison between theory and experiment.

PubMed

Makowska, Joanna; Bagińska, Katarzyna; Liwo, Adam; Chmurzyński, Lech; Scheraga, Harold A

2008-01-01

The purpose of this work was to evaluate the effect of the nature of the ionizable end groups, and the solvent, on their acid-base properties in alanine-based peptides. Hence, the acid-base properties of three alanine-based peptides: Ac-KK-(A)(7)-KK-NH(2) (KAK), Ac-OO-(A)(7)-DD-NH(2) (OAD), Ac-KK-(A)(7)-EE-NH(2) (KAE), where A, D, E, K, and O denote alanine, aspartic acid, glutamic acid, lysine, and ornithine, respectively, were determined in water and in methanol by potentiometry. With the availability of these data, the ability of two theoretical methods to simulate pH-metric titration of those peptides was assessed: (i) the electrostatically driven Monte Carlo method with the ECEPP/3 force field and the Poisson-Boltzmann approach to compute solvation energy (EDMC/PB/pH), and (ii) the molecular dynamics method with the AMBER force field and the Generalized Born model (MD/GB/pH). For OAD and KAE, pK(a1) and pK(a2) correspond to the acidic side chains. For all three compounds in both solvents, the pK(a1) value is remarkably lower than the pK(a) of a compound modeling the respective isolated side chain, which can be explained by the influence of the electrostatic field from positively charged ornithine or lysine side chains. The experimental titration curves are reproduced well by the MD/GB/pH approach, the agreement being better if restraints derived from NMR measurements are incorporated in the conformational search. Poorer agreement is achieved by the EDMC/PB/pH method.

Side-chain Engineering of Benzo[1,2-b:4,5-b’]dithiophene Core-structured Small Molecules for High-Performance Organic Solar Cells

PubMed Central

Yin, Xinxing; An, Qiaoshi; Yu, Jiangsheng; Guo, Fengning; Geng, Yongliang; Bian, Linyi; Xu, Zhongsheng; Zhou, Baojing; Xie, Linghai; Zhang, Fujun; Tang, Weihua

2016-01-01

Three novel small molecules have been developed by side-chain engineering on benzo[1,2-b:4,5-b’]dithiophene (BDT) core. The typical acceptor-donor-acceptor (A-D-A) structure is adopted with 4,8-functionalized BDT moieties as core, dioctylterthiophene as π bridge and 3-ethylrhodanine as electron-withdrawing end group. Side-chain engineering on BDT core exhibits small but measurable effect on the optoelectronic properties of small molecules. Theoretical simulation and X-ray diffraction study reveal the subtle tuning of interchain distance between conjugated backbones has large effect on the charge transport and thus the photovoltaic performance of these molecules. Bulk-heterojunction solar cells fabricated with a configuration of ITO/PEDOT:PSS/SM:PC71BM/PFN/Al exhibit a highest power conversion efficiency (PCE) of 6.99% after solvent vapor annealing. PMID:27140224

Side-chain Engineering of Benzo[1,2-b:4,5-b']dithiophene Core-structured Small Molecules for High-Performance Organic Solar Cells.

PubMed

Yin, Xinxing; An, Qiaoshi; Yu, Jiangsheng; Guo, Fengning; Geng, Yongliang; Bian, Linyi; Xu, Zhongsheng; Zhou, Baojing; Xie, Linghai; Zhang, Fujun; Tang, Weihua

2016-05-03

Three novel small molecules have been developed by side-chain engineering on benzo[1,2-b:4,5-b']dithiophene (BDT) core. The typical acceptor-donor-acceptor (A-D-A) structure is adopted with 4,8-functionalized BDT moieties as core, dioctylterthiophene as π bridge and 3-ethylrhodanine as electron-withdrawing end group. Side-chain engineering on BDT core exhibits small but measurable effect on the optoelectronic properties of small molecules. Theoretical simulation and X-ray diffraction study reveal the subtle tuning of interchain distance between conjugated backbones has large effect on the charge transport and thus the photovoltaic performance of these molecules. Bulk-heterojunction solar cells fabricated with a configuration of ITO/PEDOT:PSS/SM:PC71BM/PFN/Al exhibit a highest power conversion efficiency (PCE) of 6.99% after solvent vapor annealing.

Uncovering the determinants of a highly perturbed tyrosine pKa in the active site of ketosteroid isomerase.

PubMed

Schwans, Jason P; Sunden, Fanny; Gonzalez, Ana; Tsai, Yingssu; Herschlag, Daniel

2013-11-05

Within the idiosyncratic enzyme active-site environment, side chain and ligand pKa values can be profoundly perturbed relative to their values in aqueous solution. Whereas structural inspection of systems has often attributed perturbed pKa values to dominant contributions from placement near charged groups or within hydrophobic pockets, Tyr57 of a Pseudomonas putida ketosteroid isomerase (KSI) mutant, suggested to have a pKa perturbed by nearly 4 units to 6.3, is situated within a solvent-exposed active site devoid of cationic side chains, metal ions, or cofactors. Extensive comparisons among 45 variants with mutations in and around the KSI active site, along with protein semisynthesis, (13)C NMR spectroscopy, absorbance spectroscopy, and X-ray crystallography, was used to unravel the basis for this perturbed Tyr pKa. The results suggest that the origin of large energetic perturbations are more complex than suggested by visual inspection. For example, the introduction of positively charged residues near Tyr57 raises its pKa rather than lowers it; this effect, and part of the increase in the Tyr pKa from the introduction of nearby anionic groups, arises from accompanying active-site structural rearrangements. Other mutations with large effects also cause structural perturbations or appear to displace a structured water molecule that is part of a stabilizing hydrogen-bond network. Our results lead to a model in which three hydrogen bonds are donated to the stabilized ionized Tyr, with these hydrogen-bond donors, two Tyr side chains, and a water molecule positioned by other side chains and by a water-mediated hydrogen-bond network. These results support the notion that large energetic effects are often the consequence of multiple stabilizing interactions rather than a single dominant interaction. Most generally, this work provides a case study for how extensive and comprehensive comparisons via site-directed mutagenesis in a tight feedback loop with structural analysis can greatly facilitate our understanding of enzyme active-site energetics. The extensive data set provided may also be a valuable resource for those wishing to extensively test computational approaches for determining enzymatic pKa values and energetic effects.

Uncovering the Determinants of a Highly Perturbed Tyrosine pKa in the Active Site of Ketosteroid Isomerase†

PubMed Central

Schwans, Jason P.; Sunden, Fanny; Gonzalez, Ana; Tsai, Yingssu; Herschlag, Daniel

2013-01-01

Within the idiosyncratic enzyme active site environment, side chain and ligand pKa values can be profoundly perturbed relative to their values in aqueous solution. Whereas structural inspection of systems has often attributed perturbed pKa values to dominant contributions from placement near to charged groups or within hydrophobic pockets, Tyr57 of a P. putida ketosteroid isomerase (KSI) mutant, suggested to have a pKa perturbed by nearly 4 units to 6.3, is situated within a solvent-exposed active site devoid of cationic side chains, metal ions, or cofactors. Extensive comparisons among 45 variants with mutations in and around the KSI active site, along with protein semi-synthesis, 13C NMR spectroscopy, absorbance spectroscopy, and x-ray crystallography, was used to unravel the basis for this perturbed Tyr pKa. The results suggest that the origin of large energetic perturbations are more complex than suggested by visual inspection. For example, the introduction of positively charged residues near Tyr57 raises its pKa rather than lowers it; this effect, and part of the increase in the Tyr pKa from introduction of nearby anionic groups arise from accompanying active site structural rearrangements. Other mutations with large effects also cause structural perturbations or appear to displace a structured water molecule that is part of a stabilizing hydrogen bond network. Our results lead to a model in which three hydrogen bonds are donated to the stabilized ionized Tyr, with these hydrogen bond donors, two Tyr side chains and a water molecule, positioned by other side chains and by a water-mediated hydrogen bond network. These results support the notion that large energetic effects are often the consequence of multiple stabilizing interactions, rather than a single dominant interaction. Most generally, this work provides a case study for how extensive and comprehensive comparisons via site-directed mutagenesis in a tight feedback loop with structural analysis can greatly facilitate our understanding of enzyme active site energetics. The extensive dataset provided may also be a valuable resource for those wishing to extensively test computational approaches for determining enzymatic pKa values and energetic effects. PMID:24151972

Probing Structural Transitions in the Intrinsically Disordered C-Terminal Domain of the Measles Virus Nucleoprotein by Vibrational Spectroscopy of Cyanylated Cysteines

PubMed Central

Bischak, Connor G.; Longhi, Sonia; Snead, David M.; Costanzo, Stéphanie; Terrer, Elodie; Londergan, Casey H.

2010-01-01

Four single-cysteine variants of the intrinsically disordered C-terminal domain of the measles virus nucleoprotein (NTAIL) were cyanylated at cysteine and their infrared spectra in the C≡N stretching region were recorded both in the absence and in the presence of one of the physiological partners of NTAIL, namely the C-terminal X domain (XD) of the viral phosphoprotein. Consistent with previous studies showing that XD triggers a disorder-to-order transition within NTAIL, the C≡N stretching bands of the infrared probe were found to be significantly affected by XD, with this effect being position-dependent. When the cyanylated cysteine side chain is solvent-exposed throughout the structural transition, its changing linewidth reflects a local gain of structure. When the probe becomes partially buried due to binding, its frequency reports on the mean hydrophobicity of the microenvironment surrounding the labeled side chain of the bound form. The probe moiety is small compared to other common covalently attached spectroscopic probes, thereby minimizing possible steric hindrance/perturbation at the binding interface. These results show for the first time to our knowledge the suitability of site-specific cysteine mutagenesis followed by cyanylation and infrared spectroscopy to document structural transitions occurring within intrinsically disordered regions, with regions involved in binding and folding being identifiable at the residue level. PMID:20816082

A hierarchy of functionally important relaxations within myoglobin based on solvent effects, mutations and kinetic model.

PubMed

Dantsker, David; Samuni, Uri; Friedman, Joel M; Agmon, Noam

2005-06-01

Geminate CO rebinding in myoglobin is studied for two viscous solvents, trehalose and sol-gel (bathed in 100% glycerol) at several temperatures. Mutations in key distal hemepocket residues are used to eliminate or enhance specific relaxation modes. The time-resolved data are analyzed with a modified Agmon-Hopfield model which is capable of providing excellent fits in cases where a single relaxation mode is dominant. Using this approach, we determine the relaxation rate constants of specific functionally important modes, obtaining also their Arrhenius activation energies. We find a hierarchy of distal pocket modes controlling the rebinding kinetics. The "heme access mode" (HAM) is responsible for the major slow-down in rebinding. It is a solvent-coupled cooperative mode which restricts ligand return from the xenon cavities. Bulky side-chains, like those His64 and Trp29 (in the L29W mutant), operate like overdamped pendulums which move over and block the binding site. They may be either unslaved (His64) or moderately slaved (Trp29) to the solvent. Small side-chain relaxations, most notably of leucines, are revealed in some mutants (V68L, V68A). They are conjectured to facilitate inter-cavity ligand motion. When all relaxations are arrested (H64L in trehalose), we observe pure inhomogeneous kinetics with no temperature dependence, suggesting that proximal relaxation is not a factor on the investigated timescale.

The position 68(E11) side chain in myoglobin regulates ligand capture, bond formation with heme iron, and internal movement into the xenon cavities.

PubMed

Dantsker, David; Roche, Camille; Samuni, Uri; Blouin, George; Olson, John S; Friedman, Joel M

2005-11-18

After photodissociation, ligand rebinding to myoglobin exhibits complex kinetic patterns associated with multiple first-order geminate recombination processes occurring within the protein and a simpler bimolecular phase representing second-order ligand rebinding from the solvent. A smooth transition from cryogenic-like to solution phase properties can be obtained by using a combination of sol-gel encapsulation, addition of glycerol as a bathing medium, and temperature tuning (-15 --> 65 degrees C). This approach was applied to a series of double mutants, myoglobin CO (H64L/V68X, where X = Ala, Val, Leu, Asn, and Phe), which were designed to examine the contributions of the position 68(E11) side chain to the appearance and disappearance of internal rebinding phases in the absence of steric and polar interactions with the distal histidine. Based on the effects of viscosity, temperature, and the stereochemistry of the E11 side chain, the three major phases, B --> A, C --> A, and D --> A, can be assigned, respectively, to ligand rebinding from the following: (i) the distal heme pocket, (ii) the xenon cavities prior to large amplitude side chain conformational relaxation, and (iii) the xenon cavities after significant conformational relaxation of the position 68(E11) side chain. The relative amplitudes of the B --> A and C --> A phases depend markedly on the size and shape of the E11 side chain, which regulates sterically both ligand return to the heme iron atom and ligand migration to the xenon cavities. The internal xenon cavities provide a transient docking site that allows side chain relaxations and the entry of water into the vacated distal pocket, which in turn slows ligand recombination markedly.

Survey of Extreme Solvent Tolerance in Gram-Positive Cocci: Membrane Fatty Acid Changes in Staphylococcus haemolyticus Grown in Toluene

PubMed Central

Nielsen, Lindsey E.; Kadavy, Dana R.; Rajagopal, Soumitra; Drijber, Rhae; Nickerson, Kenneth W.

2005-01-01

We exploited the unique ecological niche of oil fly larval guts to isolate a strain of Staphylococcus haemolyticus which may be the most solvent-tolerant gram-positive bacterium yet described. This organism is able to tolerate 100% toluene, benzene, and p-xylene on plate overlays and saturating levels of these solvents in monophasic liquid cultures. A comparison of membrane fatty acids by gas chromatography after growth in liquid media with and without toluene showed that in cells continuously exposed to solvent the proportion of anteiso fatty acids increased from 25.8 to 33.7% while the proportion of 20:0 straight-chain fatty acids decreased from 19.3 to 10.1%. No changes in the membrane phospholipid composition were noted. Thus, S. haemolyticus alters its membrane fluidity via fatty acid composition to become more fluid when it is exposed to solvent. This response is opposite that commonly found in gram-negative bacteria, which change their fatty acids so that the cytoplasmic membrane is less fluid. Extreme solvent tolerance in S. haemolyticus is not accompanied by abnormal resistance to anionic or cationic detergents. Finally, six strains of Staphylococcus aureus and five strains of Staphylococcus epidermidis, which were not obtained by solvent selection, also exhibited exceptional solvent tolerance. PMID:16151101

Survey of extreme solvent tolerance in gram-positive cocci: membrane fatty acid changes in Staphylococcus haemolyticus grown in toluene.

PubMed

Nielsen, Lindsey E; Kadavy, Dana R; Rajagopal, Soumitra; Drijber, Rhae; Nickerson, Kenneth W

2005-09-01

We exploited the unique ecological niche of oil fly larval guts to isolate a strain of Staphylococcus haemolyticus which may be the most solvent-tolerant gram-positive bacterium yet described. This organism is able to tolerate 100% toluene, benzene, and p-xylene on plate overlays and saturating levels of these solvents in monophasic liquid cultures. A comparison of membrane fatty acids by gas chromatography after growth in liquid media with and without toluene showed that in cells continuously exposed to solvent the proportion of anteiso fatty acids increased from 25.8 to 33.7% while the proportion of 20:0 straight-chain fatty acids decreased from 19.3 to 10.1%. No changes in the membrane phospholipid composition were noted. Thus, S. haemolyticus alters its membrane fluidity via fatty acid composition to become more fluid when it is exposed to solvent. This response is opposite that commonly found in gram-negative bacteria, which change their fatty acids so that the cytoplasmic membrane is less fluid. Extreme solvent tolerance in S. haemolyticus is not accompanied by abnormal resistance to anionic or cationic detergents. Finally, six strains of Staphylococcus aureus and five strains of Staphylococcus epidermidis, which were not obtained by solvent selection, also exhibited exceptional solvent tolerance.

Conformation-related exciton localization and charge-pair formation in polythiophenes: ensemble and single-molecule study.

PubMed

Sugimoto, Toshikazu; Habuchi, Satoshi; Ogino, Kenji; Vacha, Martin

2009-09-10

We study conformation-dependent photophysical properties of polythiophene (PT) by molecular dynamics simulations and by ensemble and single-molecule optical experiments. We use a graft copolymer consisting of a polythiophene backbone and long polystyrene branches and compare its properties with those obtained on the same polythiophene derivative without the side chains. Coarse-grain molecular dynamics simulations show that in a poor solvent, the PT without the side chains (PT-R) forms a globulelike conformation in which distances between any two conjugated segments on the chain are within the Forster radius for efficient energy transfer. In the PT with the polystyrene branches (PT-PS), the polymer main PT chain retains an extended coillike conformation, even in a poor solvent, and the calculated distances between conjugated segments favor energy transfer only between a few neighboring chromophores. The theoretical predictions are confirmed by measurements of fluorescence anisotropy and fluorescence blinking of the polymers' single chains. High anisotropy ratios and two-state blinking in PT-R are due to localization of the exciton on a single conjugated segment. These signatures of exciton localization are absent in single chains of PT-PS. Electric-field-induced quenching measured as a function of concentration of PT dispersed in an inert matrix showed that in well-isolated chains of PT-PS, the exciton dissociation is an intrachain process and that aggregation of the PT-R chains causes an increase in quenching due to the onset of interchain interactions. Measurements of the field-induced quenching on single chains indicate that in PT-R, the exciton dissociation is a slower process that takes place only after the exciton is localized on one conjugated segment.

Solvent-Exposed Salt Bridges Influence the Kinetics of α-Helix Folding and Unfolding.

PubMed

Meuzelaar, Heleen; Tros, Martijn; Huerta-Viga, Adriana; van Dijk, Chris N; Vreede, Jocelyne; Woutersen, Sander

2014-03-06

Salt bridges are known to play an essential role in the thermodynamic stability of the folded conformation of many proteins, but their influence on the kinetics of folding remains largely unknown. Here, we investigate the effect of Glu-Arg salt bridges on the kinetics of α-helix folding using temperature-jump transient-infrared spectroscopy and steady-state UV circular dichroism. We find that geometrically optimized salt bridges (Glu - and Arg + are spaced four peptide units apart, and the Glu/Arg order is such that the side-chain rotameric preferences favor salt-bridge formation) significantly speed up folding and slow down unfolding, whereas salt bridges with unfavorable geometry slow down folding and slightly speed up unfolding. Our observations suggest a possible explanation for the surprising fact that many biologically active proteins contain salt bridges that do not stabilize the native conformation: these salt bridges might have a kinetic rather than a thermodynamic function.

Straight-Chain Alkyl Isocyanides Open the Distal Histidine Gate in Crystal Structures of Myoglobin†

PubMed Central

Smith, Rober D.; Blouin, George C.; Johnson, Kenneth A.; Phillips, George N.; Olson, John S.

2014-01-01

Crystal structures of methyl, ethyl, propyl and butyl isocyanide bound to sperm whale myoglobin (Mb) reveal two major conformations. In the in conformer, His(E7) is in a “closed” position, forcing the ligand alkyl chain to point inward. In the out conformer, His(E7) is in an “open” position, allowing the ligand side chain to point outward. A progressive increase in the population of the out conformer is observed with increasing ligand length in P21 crystals of native Mb at pH 7.0. This switch from in to out with increasing ligand size also occurs in solution as measured by the decrease in the relative intensity of the low (~2075 cm 1) versus high frequency (~2125 cm 1) isocyano bands. In contrast, all four isocyanides in P6 crystals of wild type recombinant Mb occupy the in conformation. However, mutating either His64 to Ala, creating a “hole” to solvent, or Phe46 to Val, freeing rotation of His64, causes bound butyl isocyanide to point completely outward in P6 crystals. Thus, the unfavorable hindrance caused with crowding a large alkyl side chain into the distal pocket appears to be roughly equal to that for pushing open the His(E7) gate and is easily affected by crystal packing. This structural conclusion supports the “side path” kinetic mechanism for O2 release, in which the dissociated ligand first moves toward the protein interior and then encounters steric resistance, which is roughly equal to that for escaping to solvent through the His(E7) channel. PMID:20481504

Role of Tryptophan Side Chain Dynamics on the Trp-Cage Mini-Protein Folding Studied by Molecular Dynamics Simulations

PubMed Central

Kannan, Srinivasaraghavan; Zacharias, Martin

2014-01-01

The 20 residue Trp-cage mini-protein is one of smallest proteins that adopt a stable folded structure containing also well-defined secondary structure elements. The hydrophobic core is arranged around a single central Trp residue. Despite several experimental and simulation studies the detailed folding mechanism of the Trp-cage protein is still not completely understood. Starting from fully extended as well as from partially folded Trp-cage structures a series of molecular dynamics simulations in explicit solvent and using four different force fields was performed. All simulations resulted in rapid collapse of the protein to on average relatively compact states. The simulations indicate a significant dependence of the speed of folding to near-native states on the side chain rotamer state of the central Trp residue. Whereas the majority of intermediate start structures with the central Trp side chain in a near-native rotameric state folded successfully within less than 100 ns only a fraction of start structures reached near-native folded states with an initially non-native Trp side chain rotamer state. Weak restraining of the Trp side chain dihedral angles to the state in the folded protein resulted in significant acceleration of the folding both starting from fully extended or intermediate conformations. The results indicate that the side chain conformation of the central Trp residue can create a significant barrier for controlling transitions to a near native folded structure. Similar mechanisms might be of importance for the folding of other protein structures. PMID:24563686

RDC-enhanced structure calculation of a β-heptapeptide in methanol.

PubMed

Rigling, Carla; Ebert, Marc-Olivier

2017-07-01

Residual dipolar couplings (RDCs) are a rich source of structural information that goes beyond the range covered by the nuclear Overhauser effect or scalar coupling constants. They can only be measured in partially oriented samples. RDC studies of peptides in organic solvents have so far been focused on samples in chloroform or DMSO. Here, we show that stretched poly(vinyl acetate) can be used for the partial alignment of a linear β-peptide with proteinogenic side chains in methanol. 1 D CH , 1 D NH , and 2 D HH RDCs were collected with this sample and included as restraints in a simulated annealing calculation. Incorporation of RDCs in the structure calculation process improves the long-range definition in the backbone of the resulting 3 14 -helix and uncovers side-chain mobility. Experimental side-chain RDCs of the central leucine and valine residues are in good agreement with predicted values from a local three-state model. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Free Energy Perturbation Calculations of the Thermodynamics of Protein Side-Chain Mutations.

PubMed

Steinbrecher, Thomas; Abel, Robert; Clark, Anthony; Friesner, Richard

2017-04-07

Protein side-chain mutation is fundamental both to natural evolutionary processes and to the engineering of protein therapeutics, which constitute an increasing fraction of important medications. Molecular simulation enables the prediction of the effects of mutation on properties such as binding affinity, secondary and tertiary structure, conformational dynamics, and thermal stability. A number of widely differing approaches have been applied to these predictions, including sequence-based algorithms, knowledge-based potential functions, and all-atom molecular mechanics calculations. Free energy perturbation theory, employing all-atom and explicit-solvent molecular dynamics simulations, is a rigorous physics-based approach for calculating thermodynamic effects of, for example, protein side-chain mutations. Over the past several years, we have initiated an investigation of the ability of our most recent free energy perturbation methodology to model the thermodynamics of protein mutation for two specific problems: protein-protein binding affinities and protein thermal stability. We highlight recent advances in the field and outline current and future challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Advanced Polymer Network Structures

DTIC Science & Technology

2016-02-01

double networks in a single step was identified from coarse-grained molecular dynamics simulations of polymer solvents bearing rigid side chains dissolved...in a polymer network. Coarse-grained molecular dynamics simulations also explored the mechanical behavior of traditional double networks and...DRI), polymer networks, polymer gels, molecular dynamics simulations , double networks 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

Neutron Structure of Human Carbonic Anhydrase II: Implications for Proton Transfer†

PubMed Central

Fisher, S. Zoë; Kovalevsky, Andrey Y.; Domsic, John F.; Mustyakimov, Marat; McKenna, Robert; Silverman, David N.; Langan, Paul A.

2010-01-01

Human carbonic anhydrase II (HCA II) catalyzes the reversible hydration of carbon dioxide to form bicarbonate and a proton. Despite many high-resolution X-ray crystal structures, mutagenesis, and kinetic data, the structural details of the active site, especially the proton transfer pathway, are unclear. A large HCA II crystal was prepared at pH 9.0 and subjected to vapor H–D exchange to replace labile hydrogens with deuteriums. Neutron diffraction studies were conducted at the Protein Crystallography Station at Los Alamos National Laboratory. The structure to 2.0 Å resolution reveals several interesting active site features: (1) the Zn-bound solvent appearing to be predominantly a D2O molecule, (2) the orientation and hydrogen bonding pattern of solvent molecules in the active site cavity, (3) the side chain of His64 being unprotonated (neutral) and predominantly in an inward conformation pointing toward the zinc, and (4) the phenolic side chain of Tyr7 appearing to be unprotonated. The implications of these details are discussed, and a proposed mechanism for proton transfer is presented. PMID:20025241

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwon, Hyock Joo; Abi-Mosleh, Lina; Wang, Michael L.

LDL delivers cholesterol to lysosomes by receptor-mediated endocytosis. Exit of cholesterol from lysosomes requires two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. NPC2 binds cholesterol with its isooctyl side chain buried and its 3{beta}-hydroxyl exposed. Here, we describe high-resolution structures of the N-terminal domain (NTD) of NPC1 and complexes with cholesterol and 25-hydroxycholesterol. NPC1(NTD) binds cholesterol in an orientation opposite to NPC2: 3{beta}-hydroxyl buried and isooctyl side chain exposed. Cholesterol transfer from NPC2 to NPC1(NTD) requires reorientation of a helical subdomain in NPC1(NTD), enlarging the opening for cholesterol entry. NPC1 with point mutations in this subdomain (distinct from themore » binding subdomain) cannot accept cholesterol from NPC2 and cannot restore cholesterol exit from lysosomes in NPC1-deficient cells. We propose a working model wherein after lysosomal hydrolysis of LDL-cholesteryl esters, cholesterol binds NPC2, which transfers it to NPC1(NTD), reversing its orientation and allowing insertion of its isooctyl side chain into the outer lysosomal membranes.« less

Arginine residues on the opposite side of the active site stimulate the catalysis of ribosome depurination by ricin A chain by interacting with the P-protein stalk.

PubMed

Li, Xiao-Ping; Kahn, Peter C; Kahn, Jennifer Nielsen; Grela, Przemyslaw; Tumer, Nilgun E

2013-10-18

Ricin inhibits protein synthesis by depurinating the α-sarcin/ricin loop (SRL). Ricin holotoxin does not inhibit translation unless the disulfide bond between the A (RTA) and B (RTB) subunits is reduced. Ricin holotoxin did not bind ribosomes or depurinate them but could depurinate free RNA. When RTA is separated from RTB, arginine residues located at the interface are exposed to the solvent. Because this positively charged region, but not the active site, is blocked by RTB, we mutated arginine residues at or near the interface of RTB to determine if they are critical for ribosome binding. These variants were structurally similar to wild type RTA but could not bind ribosomes. Their K(m) values and catalytic rates (k(cat)) for an SRL mimic RNA were similar to those of wild type, indicating that their activity was not altered. However, they showed an up to 5-fold increase in K(m) and up to 38-fold decrease in kcat toward ribosomes. These results suggest that the stalk binding stimulates the catalysis of ribosome depurination by RTA. The mutated arginines have side chains behind the active site cleft, indicating that the ribosome binding surface of RTA is on the opposite side of the surface that interacts with the SRL. We propose that stalk binding stimulates the catalysis of ribosome depurination by orienting the active site of RTA toward the SRL and thereby allows docking of the target adenine into the active site. This model may apply to the translation factors that interact with the stalk.

Roles of urea and TMAO on the interaction between extended non-polar peptides

NASA Astrophysics Data System (ADS)

Su, Zhaoqian; Dias, Cristiano

Urea and trimethylamine n-oxide (TMAO) are small molecules known to destabilize and stabilize, respectively, the structure of proteins when added to aqueous solution. To unravel the molecular mechanisms of these cosolvents on protein structure we perform explicit all-atom molecular dynamics simulations of extended poly-alanine and polyleucine dimers. We use an umbrella sampling protocol to compute the potential of mean force (PMF) of dimers at different concentrations of urea and TMAO. We find that the large non-polar side chain of leucine is affected by urea whereas backbone atoms and alanine's side chain are not. Urea is found to occupy positions between leucine's side chains that are not accessible to water. This accounts for extra Lennard-Jones bonds between urea and side chains that favors the unfolded state. These bonds compete with urea-solvent interactions that favor the folded state. The sum of these two energetic terms provide the enthalpic driving force for unfolding. We show here that this enthalpy correlate with the potential of mean force of poly-leucine dimers. Moreover, the framework developed here is general and may be used to provide insights into effects of other small molecules on protein interactions. The effect of the TMAO will be in the presentation. Department of Physics, University Heights, Newark, New Jersey, 07102-1982.

Quantitative Protein Topography Analysis and High-Resolution Structure Prediction Using Hydroxyl Radical Labeling and Tandem-Ion Mass Spectrometry (MS)*

PubMed Central

Kaur, Parminder; Kiselar, Janna; Yang, Sichun; Chance, Mark R.

2015-01-01

Hydroxyl radical footprinting based MS for protein structure assessment has the goal of understanding ligand induced conformational changes and macromolecular interactions, for example, protein tertiary and quaternary structure, but the structural resolution provided by typical peptide-level quantification is limiting. In this work, we present experimental strategies using tandem-MS fragmentation to increase the spatial resolution of the technique to the single residue level to provide a high precision tool for molecular biophysics research. Overall, in this study we demonstrated an eightfold increase in structural resolution compared with peptide level assessments. In addition, to provide a quantitative analysis of residue based solvent accessibility and protein topography as a basis for high-resolution structure prediction; we illustrate strategies of data transformation using the relative reactivity of side chains as a normalization strategy and predict side-chain surface area from the footprinting data. We tested the methods by examination of Ca+2-calmodulin showing highly significant correlations between surface area and side-chain contact predictions for individual side chains and the crystal structure. Tandem ion based hydroxyl radical footprinting-MS provides quantitative high-resolution protein topology information in solution that can fill existing gaps in structure determination for large proteins and macromolecular complexes. PMID:25687570

N,N'-DICYCLOHEXYL-N"-ISOTRIDECYLGUANIDINE AS SUPPRESSOR FOR THE NEXT GENERATION CAUSTIC SIDE SOLVENT EXTRACTION (NG-CSSX) PROCESS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duncan, Nathan C; Roach, Benjamin D; Williams, Neil J

2012-01-01

ABSTRACT The purity, concentration, and source of the N,N'-dicyclohexyl-N"-isotridecylguanidine (DCiTG) suppressor (guanidine) used in the NG-CSSX process were found to influence solvent performance. As the starting isotridecanol used in the preparation of DCiTG is comprised of a mixture of branched-chain aliphatic alcohols, varying in composition with manufacturer, the resulting DCiTG itself is a mixture. Thus, it is necessary to address how the solvent performance will be affected by the different preparations of the DCiTG solvent component. In this study, four preparations of DCiTG from three sources were analyzed and evaluated for purity and performance, both in the absence and presencemore » of an anionic surfactant impurity.« less

Solvent-free iodination of organic molecules using the I(2)/urea-H(2)O(2) reagent system.

PubMed

Pavlinac, Jasminka; Zupan, Marko; Stavber, Stojan

2007-02-21

Introduction of iodine under solvent-free conditions into several aromatic compounds activated toward electrophilic functionalization was found to proceed efficiently using elemental iodine in the presence of a solid oxidizer, the urea-H(2)O(2) (UHP) adduct. Two types of iodo-functionalization through an electrophilic process were observed: iodination of an aromatic ring, and side-chain iodo-functionalization in the case of arylalkyl ketones. Two reaction routes were established based on the required substrate : iodine : oxidizer ratio for the most efficient iodo-transformation, and the role of UHP was elucidated in each route. The first, requiring a 1 : 0.5 : 0.6 stoichiometric ratio of substrate to iodine to UHP, followed the atom economy concept in regard to iodine and was valid in the case of aniline, 4-t-Bu-phenol, 1,2-dimethoxy benzene, 1,3-dimethoxy benzene, 1,2,3-trimethoxy benzene, 1,2,4-trimethoxy benzene, 1,3,5-trimethoxy benzene, 1-indanone and 1-tetralone. The second reaction route, where a 1 : 1 : 1 stoichiometric ratio of substrate : I(2) : UHP was needed for efficient iodination, was suitable for side-chain iodo-functionalization of acetophenone and methoxy-substituted acetophenones. Moreover, addition of iodine to 1-octene and some phenylacetylenic derivatives was found to proceed efficiently without the presence of any oxidizer and solvent at room temperature.

Enthalpy characteristics of the dissolution of L-valine in water/formamide mixtures at 298.15 K

NASA Astrophysics Data System (ADS)

Smirnov, V. I.; Badelin, V. G.

2016-11-01

The thermochemical dissolution of L-valine in solvent mixtures H2O + (formamide, N-methylformamide, and N, N-dimethylformamide) is studied at an organic component concentration of x 2 = 0-0.35 molar fractions and a temperature of 298.15 K. The experimental data are used to calculate standard enthalpies of dissolution, the transferring of L-valine from water to a mixed solvent, and the enthalpy coefficients of pairwise interactions ( h xy ) with organic solvent molecules. The correlation between the enthalpy characteristics of the dissolution of L-valine with the composition of aqueous organic mixtures and the nature of the organic solvent (its physicochemical properties) is determined. A comparative analysis of the values of h xy of a number of aliphatic L-amino acids in similar solvent mixtures with the hydrophobicity parameters of their side chains is performed.

Homoallylglycine residues are superior precursors to orthogonally modified thioether containing polypeptides.

PubMed

Perlin, Pesach; Gharakhanian, Eric G; Deming, Timothy J

2018-06-12

Homoallylglycine N-carboxyanhydride, Hag NCA, monomers were synthesized and used to prepare polypeptides containing Hag segments with controllable lengths of up to 245 repeats. Poly(l-homoallylglycine), GHA, was found to adopt an α-helical conformation, which provided good solubility in organic solvents and allowed high yield functionalization of its alkene side-chains via radical promoted addition of thiols. The conformations of these derivatives were shown to be switchable between α-helical and disordered states in aqueous media using thioether alkylation or oxidation reactions. Incorporation of GHA segments into block copolymers with poly(l-methionine), M, segments provided a means to orthogonally modify thioether side-chains different ways in separate copolypeptide domains. This approach allows preparation of functional polypeptides containing discrete domains of oxidized and alkylated thioether containing residues, where chain conformation and functionality of each domain can be independently modified.

Examination and Manipulation of Protein Surface Charge in Solution with Electrospray Ionization Mass Spectrometry

ERIC Educational Resources Information Center

Gross, Deborah S.; Van Ryswyk, Hal

2014-01-01

Electrospray ionization mass spectrometry (ESI-MS) is a powerful tool for examining the charge of proteins in solution. The charge can be manipulated through choice of solvent and pH. Furthermore, solution-accessible, protonated lysine side chains can be specifically tagged with 18-crown-6 ether to form noncovalent adducts. Chemical derivatization…

How accurately do force fields represent protein side chain ensembles?

PubMed

Petrović, Dušan; Wang, Xue; Strodel, Birgit

2018-05-23

Although the protein backbone is the most fundamental part of the structure, the fine-tuning of side-chain conformations is important for protein function, for example, in protein-protein and protein-ligand interactions, and also in enzyme catalysis. While several benchmarks testing the performance of protein force fields for side chain properties have already been published, they often considered only a few force fields and were not tested against the same experimental observables; hence, they are not directly comparable. In this work, we explore the ability of twelve force fields, which are different flavors of AMBER, CHARMM, OPLS, or GROMOS, to reproduce average rotamer angles and rotamer populations obtained from extensive NMR studies of the 3 J and residual dipolar coupling constants for two small proteins: ubiquitin and GB3. Based on a total of 196 μs sampling time, our results reveal that all force fields identify the correct side chain angles, while the AMBER and CHARMM force fields clearly outperform the OPLS and GROMOS force fields in estimating rotamer populations. The three best force fields for representing the protein side chain dynamics are AMBER 14SB, AMBER 99SB*-ILDN, and CHARMM36. Furthermore, we observe that the side chain ensembles of buried amino acid residues are generally more accurately represented than those of the surface exposed residues. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Self-Organization of Polymer Brush Layers in a Poor Solvent

NASA Astrophysics Data System (ADS)

Karim, A.; Tsukruk, V. V.; Douglas, J. F.; Satija, S. K.; Fetters, L. J.; Reneker, D. H.; Foster, M. D.

1995-10-01

Synthesis of densely grafted polymer brushes from good solvent polymer solutions is difficult when the surface interaction is only weakly attractive because of the strong steric repulsion between the polymer chains. To circumvent this difficulty we graft polymer layers in a poor solvent to exploit attractive polymer-polymer interactions which largely nullify the repulsive steric interactions. This simple strategy gives rise to densely grafted and homogeneous polymer brush layers. Model end-grafted polystyrene chains (M_w = 105,000) are prepared in the poor solvent cyclohexane (9.5 °C) where the chains are chemically attached to the surface utilizing a trichlorosilane end-group. Polished silicon wafers were then exposed to the reactive polymer solutions for a series of “induction times” tau_I and the evolving layer was characterized by X-ray reflectivity and atomic force microscopy. Distinct morphologies were found depending on tau_I. For short tau_I, corresponding to a grafting density less than 5 mg/m^2, the grafted layer forms an inhomogeneous island-like structure. At intermediate tau_I, where the coverage becomes percolating, a surface pattern develops which appears similar to spinodal decomposition in bulk solution. Finally, after sufficiently long tau_I, a dense and nearly homogeneous layer with a sharp interface is formed which does not exhibit surface pattern formation. The stages of brush growth are discussed qualitatively in terms of a random deposition model.

Direct observation of backbone planarization via side-chain alignment in single bulky-substituted polythiophenes

NASA Astrophysics Data System (ADS)

Raithel, Dominic; Simine, Lena; Pickel, Sebastian; Schötz, Konstantin; Panzer, Fabian; Baderschneider, Sebastian; Schiefer, Daniel; Lohwasser, Ruth; Köhler, Jürgen; Thelakkat, Mukundan; Sommer, Michael; Köhler, Anna; Rossky, Peter J.; Hildner, Richard

2018-03-01

The backbone conformation of conjugated polymers affects, to a large extent, their optical and electronic properties. The usually flexible substituents provide solubility and influence the packing behavior of conjugated polymers in films or in bad solvents. However, the role of the side chains in determining and potentially controlling the backbone conformation, and thus the optical and electronic properties on the single polymer level, is currently under debate. Here, we investigate directly the impact of the side chains by studying the bulky-substituted poly(3-(2,5-dioctylphenyl)thiophene) (PDOPT) and the common poly(3-hexylthiophene) (P3HT), both with a defined molecular weight and high regioregularity, using low-temperature single-chain photoluminescence (PL) spectroscopy and quantum-classical simulations. Surprisingly, the optical transition energy of PDOPT is significantly (˜2,000 cm‑1 or 0.25 eV) red-shifted relative to P3HT despite a higher static and dynamic disorder in the former. We ascribe this red shift to a side-chain induced backbone planarization in PDOPT, supported by temperature-dependent ensemble PL spectroscopy. Our atomistic simulations reveal that the bulkier 2,5-dioctylphenyl side chains of PDOPT adopt a clear secondary helical structural motif and thus protect conjugation, i.e., enforce backbone planarity, whereas, for P3HT, this is not the case. These different degrees of planarity in both thiophenes do not result in different conjugation lengths, which we found to be similar. It is rather the stronger electronic coupling between the repeating units in the more planar PDOPT which gives rise to the observed spectral red shift as well as to a reduced calculated electron‑hole polarization.

Evidence of a reverse side-chain effect of tris(pentafluoroethyl)trifluorophosphate [FAP]-based ionic liquids against pathogenic bacteria.

PubMed

Weyhing-Zerrer, Nadine; Kalb, Roland; Oßmer, Rolf; Rossmanith, Peter; Mester, Patrick

2018-02-01

Increased interest in ionic liquids (ILs) is due to their designable and tunable unique physicochemical properties, which are utilized for a wide variety of chemical and biotechnological applications. ILs containing the tris(pentafluoroethyl)trifluorophosphate ([FAP]) anion have been shown to have excellent hydrolytic, electrochemical and thermal stability and have been successfully used in various applications. In the present study the influence of the cation on the toxicity of the [FAP] anion was investigated. Due to the properties of [FAP] ILs, the IL-toxicity of seven cations with [FAP] compared to [Cl] was examined by determination of minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) on six Gram-positive and six Gram-negative clinically-relevant bacteria. For the first time, to our knowledge, the results provide evidence for a decrease in toxicity with increasing alkyl side-chain length, indicating that the combination of both ions is responsible for this 'reverse side-chain effect'. These findings could portend development of new non-toxic ILs as green alternatives to conventional organic solvents. Copyright © 2017 Elsevier Inc. All rights reserved.

Crystal structure and novel recognition motif of rho ADP-ribosylating C3 exoenzyme from Clostridium botulinum: structural insights for recognition specificity and catalysis.

PubMed

Han, S; Arvai, A S; Clancy, S B; Tainer, J A

2001-01-05

Clostridium botulinum C3 exoenzyme inactivates the small GTP-binding protein family Rho by ADP-ribosylating asparagine 41, which depolymerizes the actin cytoskeleton. C3 thus represents a major family of the bacterial toxins that transfer the ADP-ribose moiety of NAD to specific amino acids in acceptor proteins to modify key biological activities in eukaryotic cells, including protein synthesis, differentiation, transformation, and intracellular signaling. The 1.7 A resolution C3 exoenzyme structure establishes the conserved features of the core NAD-binding beta-sandwich fold with other ADP-ribosylating toxins despite little sequence conservation. Importantly, the central core of the C3 exoenzyme structure is distinguished by the absence of an active site loop observed in many other ADP-ribosylating toxins. Unlike the ADP-ribosylating toxins that possess the active site loop near the central core, the C3 exoenzyme replaces the active site loop with an alpha-helix, alpha3. Moreover, structural and sequence similarities with the catalytic domain of vegetative insecticidal protein 2 (VIP2), an actin ADP-ribosyltransferase, unexpectedly implicates two adjacent, protruding turns, which join beta5 and beta6 of the toxin core fold, as a novel recognition specificity motif for this newly defined toxin family. Turn 1 evidently positions the solvent-exposed, aromatic side-chain of Phe209 to interact with the hydrophobic region of Rho adjacent to its GTP-binding site. Turn 2 evidently both places the Gln212 side-chain for hydrogen bonding to recognize Rho Asn41 for nucleophilic attack on the anomeric carbon of NAD ribose and holds the key Glu214 catalytic side-chain in the adjacent catalytic pocket. This proposed bipartite ADP-ribosylating toxin turn-turn (ARTT) motif places the VIP2 and C3 toxin classes into a single ARTT family characterized by analogous target protein recognition via turn 1 aromatic and turn 2 hydrogen-bonding side-chain moieties. Turn 2 centrally anchors the catalytic Glu214 within the ARTT motif, and furthermore distinguishes the C3 toxin class by a conserved turn 2 Gln and the VIP2 binary toxin class by a conserved turn 2 Glu for appropriate target side-chain hydrogen-bonding recognition. Taken together, these structural results provide a molecular basis for understanding the coupled activity and recognition specificity for C3 and for the newly defined ARTT toxin family, which acts in the depolymerization of the actin cytoskeleton. This beta5 to beta6 region of the toxin fold represents an experimentally testable and potentially general recognition motif region for other ADP-ribosylating toxins that have a similar beta-structure framework. Copyright 2001 Academic Press.

Structural stability of proteins in aqueous and nonpolar environments

NASA Astrophysics Data System (ADS)

Yasuda, Satoshi; Oshima, Hiraku; Kinoshita, Masahiro

2012-10-01

A protein folds into its native structure with the α-helix and/or β-sheet in aqueous solution under the physiological condition. The relative content of these secondary structures largely varies from protein to protein. However, such structural variability is not exhibited in nonaqueous environment. For example, there is a strong trend that alcohol induces a protein to form α-helices, and many of the membrane proteins within the lipid bilayer consists of α-helices. Here we investigate the structural stability of proteins in aqueous and nonpolar environments using our recently developed free-energy function F = (Λ - TS)/(kBT0) = Λ/(kBT0) - S/kB (T0 = 298 K and the absolute temperature T is set at T0) which is based on statistical thermodynamics. Λ/(kBT0) and S/kB are the energetic and entropic components, respectively, and kB is Boltzmann's constant. A smaller value of the positive quantity, -S, represents higher efficiency of the backbone and side-chain packing promoted by the entropic effect arising from the translational displacement of solvent molecules or the CH2, CH3, and CH groups which constitute nonpolar chains of lipid molecules. As for Λ, in aqueous solution, a transition to a more compact structure of a protein accompanies the break of protein-solvent hydrogen bonds: As the number of donors and acceptors buried without protein intramolecular hydrogen bonding increases, Λ becomes higher. In nonpolar solvent, lower Λ simply implies more intramolecular hydrogen bonds formed. We find the following. The α-helix and β-sheet are advantageous with respect to -S as well as Λ and to be formed as much as possible. In aqueous solution, the solvent-entropy effect on the structural stability is so strong that the close packing of side chains is dominantly important, and the α-helix and β-sheet contents are judiciously adjusted to accomplish it. In nonpolar solvent, the solvent-entropy effect is substantially weaker than in aqueous solution. Λ is crucial and the α-helix is more stable than the β-sheet in terms of Λ, which develops a tendency that α-helices are exclusively chosen. For a membrane protein, α-helices are stabilized as fundamental structural units for the same reason, but their arrangement is performed through the entropic effect mentioned above.

Iodination of insulin in aqueous and organic solvents

PubMed Central

Massaglia, A.; Rosa, U.; Rialdi, G.; Rossi, C. A.

1969-01-01

1. The iodination of insulin was studied under various experimental conditions in aqueous media and in some organic solvents, by measuring separately the uptake of iodine by the four tyrosyl groups and the relative amounts of monoiodotyrosine and di-iodotyrosine that are formed. In aqueous media from pH1 to pH9 the iodination occurs predominantly on the tyrosyl groups of the A chain. Some organic solvents increase the iodine uptake of the B-chain tyrosyl groups. Their efficacy in promoting iodination of Tyr-B-16 and Tyr-B-26 is in the order: ethylene glycol and propylene glycol≃methanol and ethanol>dioxan>8m-urea. 2. It is suggested that each of the four tyrosyl groups in insulin has a different environment: Tyr-A-14 is fully exposed to the solvent; Tyr-A-19 is sterically influenced by the environmental structure, possibly by the vicinity of a disulphide interchain bond; Tyr-B-16 is embedded into a non-polar area whose stability is virtually independent of the molecular conformation; Tyr-B-26 is probably in a situation similar to Tyr-B-16 with the difference that its non-polar environment depends on the preservation of the native structure. PMID:5346365

Brush-Like Polymers: New Design Platforms for Soft, Dry Materials with Unique Property Relations

NASA Astrophysics Data System (ADS)

Daniel, William Francis McKemie, Jr.

Elastomers represent a unique class of engineering materials due to their light weight, low cost, and desirable combination of softness (105 -107 Pa) and large extensibilities (up to 1000%). Despite these advantages, there exist applications that require many times softer modulus, greater extensibility, and stronger strain hardening for the purpose of mimicking the mechanical properties of systems such as biological tissues. Until recently, only liquid-filled gels were suitable materials for such applications, including soft robotics and implants. A considerable amount of work has been done to create gels with superior properties, but despite unique strengths they also suffer from unique weaknesses. This class of material displays fundamental limitations in the form of heterogeneous structures, solvent loss and phase transitions at extreme temperatures, and loss of liquid fraction upon high deformations. In gels the solvent fraction also introduces a large solvent/polymer interaction parameter which must be carefully considered when designing the final mechanical properties. These energetic considerations further exaggerate the capacity for inconstant mechanical properties caused by fluctuations of the solvent fraction. In order to overcome these weaknesses, a new platform for single component materials with low modulus (<105 Pa) must be developed. Single component systems do not suffer from compositional changes over time and display more stable performance in a wider variety of temperatures and humidity conditions. A solvent-free system also has the potential to be homogeneous which replaces the large energetic interactions with comparatively small architectural interaction parameters. If a solvent-free alternative to liquid-filled gels is to be created, we must first consider the fundamental barrier to softer elastomers, i.e. entanglements - intrinsic topological restrains which define a lower limit of modulus ( 105 Pa). These entanglements are determined by chemistry specific parameters (repeat unit volume and Kuhn segment size) in the polymer liquid (melt) prior to crosslinking. Previous solvent free replacements for gels include elastomers end-linked in semidilute conditions. These materials are generated through crosslinking telechelic polymer chains in semidilute solutions at the onset of chain overlap. At such low polymer concentrations entanglements are greatly diluted and once the resulting gel is dried it creates a supersoft and super-elastic network. Although such methods have successfully generated materials with moduli below the 105 Pa limit and high extensibilities ( 1000%) they present their own limitations. Firstly, the semidilute crosslinking methods uses an impractically large volume of solvent which is unattractive in industry. Second, producing and crosslinking large monodisperse telechelic chains is a nontrivial process leading to large uncertainties in the final network architecture and properties. Specifically, telechelics have a distribution of end-to-end distances and in semidilute solutions with extremely low fraction of chain ends the crosslink reaction is diffusion limited, very slow, and imprecise. In order to achieve a superior solvent-free platform, we propose alteration of mechanical properties through the architectural disentanglement of brush-like polymer structures. In recent year there has been an increase in the synthetic conditions and crosslinking schemes available for producing brush-like structures. This makes brush-like materials an attractive alternative to more restrictive methods such as end-linking. Standard networks have one major control factor outside of chemistry, the network stand length. Brush-like architectures are created from long strands with regularly grafted side chains creating three characteristic length scales which may be independently manipulated. In collaboration with M. Rubinstein, we have utilized bottlebrush polymer architectures (a densely grafted brush-like polymer) to experimentally verify theoretical predictions of disentangled bottlebrush melts. By attaching well-defined side chains onto long polymer backbones, individual polymer strands are separated in space (similar to dilution with solvent) accompanied by a comparatively small increase in the rigidity of the strands. The end result is an architectural disentangled melt with an entanglement plateau modulus as much as three orders of magnitude lower than typical linear polymers and a broadly expanded potential for extensibility once crosslinked.

Structural and kinetic mapping of side-chain exposure onto the protein energy landscape.

PubMed

Bernstein, Rachel; Schmidt, Kierstin L; Harbury, Pehr B; Marqusee, Susan

2011-06-28

Identification and characterization of structural fluctuations that occur under native conditions is crucial for understanding protein folding and function, but such fluctuations are often rare and transient, making them difficult to study. Native-state hydrogen exchange (NSHX) has been a powerful tool for identifying such rarely populated conformations, but it generally reveals no information about the placement of these species along the folding reaction coordinate or the barriers separating them from the folded state and provides little insight into side-chain packing. To complement such studies, we have performed native-state alkyl-proton exchange, a method analogous to NSHX that monitors cysteine modification rather than backbone amide exchange, to examine the folding landscape of Escherichia coli ribonuclease H, a protein well characterized by hydrogen exchange. We have chosen experimental conditions such that the rate-limiting barrier acts as a kinetic partition: residues that become exposed only upon crossing the unfolding barrier are modified in the EX1 regime (alkylation rates report on the rate of unfolding), while those exposed on the native side of the barrier are modified predominantly in the EX2 regime (alkylation rates report on equilibrium populations). This kinetic partitioning allows for identification and placement of partially unfolded forms along the reaction coordinate. Using this approach we detect previously unidentified, rarely populated conformations residing on the native side of the barrier and identify side chains that are modified only upon crossing the unfolding barrier. Thus, in a single experiment under native conditions, both sides of the rate-limiting barrier are investigated.

Structural and kinetic mapping of side-chain exposure onto the protein energy landscape

PubMed Central

Bernstein, Rachel; Schmidt, Kierstin L.; Harbury, Pehr B.; Marqusee, Susan

2011-01-01

Identification and characterization of structural fluctuations that occur under native conditions is crucial for understanding protein folding and function, but such fluctuations are often rare and transient, making them difficult to study. Native-state hydrogen exchange (NSHX) has been a powerful tool for identifying such rarely populated conformations, but it generally reveals no information about the placement of these species along the folding reaction coordinate or the barriers separating them from the folded state and provides little insight into side-chain packing. To complement such studies, we have performed native-state alkyl-proton exchange, a method analogous to NSHX that monitors cysteine modification rather than backbone amide exchange, to examine the folding landscape of Escherichia coli ribonuclease H, a protein well characterized by hydrogen exchange. We have chosen experimental conditions such that the rate-limiting barrier acts as a kinetic partition: residues that become exposed only upon crossing the unfolding barrier are modified in the EX1 regime (alkylation rates report on the rate of unfolding), while those exposed on the native side of the barrier are modified predominantly in the EX2 regime (alkylation rates report on equilibrium populations). This kinetic partitioning allows for identification and placement of partially unfolded forms along the reaction coordinate. Using this approach we detect previously unidentified, rarely populated conformations residing on the native side of the barrier and identify side chains that are modified only upon crossing the unfolding barrier. Thus, in a single experiment under native conditions, both sides of the rate-limiting barrier are investigated. PMID:21670244

Investigation of light-induced conformation changes in spiropyran-modified succinylated poly(L-lysine).

PubMed

Cooper, T M; Stone, M O; Natarajan, L V; Crane, R L

1995-08-01

To determine the maximum range of coupling between side-chain photochromism and polypeptide conformation change, we modified the carboxylate side chains of succinylated poly(L-lysine) with a spiropyran to form polypeptide I. The extent of modification was determined to be 35.5%. The spacer group length between the polypeptide alpha-carbon and the dye was 12 atoms, providing minimum polypeptide-dye interaction. Conformation changes were monitored by circular dichroism as a function of light adaptation and solvent composition (hexafluoroisopropanol [HFIP] vs trifluoroethanol [TFE]). Under all solvent compositions, the dark-adapted dye was in the merocyanine form. Light adaptation by visible light converted the dye to the spiropyran form. When dissolved in TFE, I adopted a helical conformation insensitive to light adaptation. With increasing percentage HFIP, a solvent-induced helix-to-coil transition was observed around 80% (vol/vol) HFIP. At 100% HFIP, both light- and dark-adapted forms of I were in the coil state. Near the midpoint of the solvent-induced helix-to-coil transition, light adaptation caused conformation changes. Applying helix-to-coil transition theory, we measured a statistically significant difference in coil segment-HFIP binding constant for light- vs dark-adapted solutions (6.38 +/- 0.03 M-1 vs 6.56 +/- 0.03 M-1), but not for the nucleation parameter sigma (1.2 +/- 0.4 10(-3) vs 1.3 +/- 0.3 x 10(-3). The small binding constant difference translated to a light-induced binding energy difference of 17 cal/mol/monomer. Near the midpoint of the helix-to-coil transition, collective interactions between monomer units made possible the translation of a small energy difference (less than RT) into large macromolecular conformation changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of intra- and inter-sheet interactions in short peptide self-assembly by acetonitrile in aqueous solution

NASA Astrophysics Data System (ADS)

Deng, Li; Zhao, Yurong; Zhou, Peng; Xu, Hai; Wang, Yanting

2016-12-01

Besides our previous experimental discovery (Zhao Y R, et al. 2015 Langmuir, 31, 12975) that acetonitrile (ACN) can tune the morphological features of nanostructures self-assembled by short peptides KIIIIK (KI4K) in aqueous solution, further experiments reported in this work demonstrate that ACN can also tune the mass of the self-assembled nanostructures. To understand the microscopic mechanism how ACN molecules interfere peptide self-assembly process, we conducted a series of molecular dynamics simulations on a monomer, a cross-β sheet structure, and a proto-fibril of KI4K in pure water, pure ACN, and ACN-water mixtures, respectively. The simulation results indicate that ACN enhances the intra-sheet interaction dominated by the hydrogen bonding (H-bonding) interactions between peptide backbones, but weakens the inter-sheet interaction dominated by the interactions between hydrophobic side chains. Through analyzing the correlations between different groups of solvent and peptides and the solvent behaviors around the proto-fibril, we have found that both the polar and nonpolar groups of ACN play significant roles in causing the opposite effects on intermolecular interactions among peptides. The weaker correlation of the polar group of ACN than water molecule with the peptide backbone enhances H-bonding interactions between peptides in the proto-fibril. The stronger correlation of the nonpolar group of ACN than water molecule with the peptide side chain leads to the accumulation of ACN molecules around the proto-fibril with their hydrophilic groups exposed to water, which in turn allows more water molecules close to the proto-fibril surface and weakens the inter-sheet interactions. The two opposite effects caused by ACN form a microscopic mechanism clearly explaining our experimental observations. Project supported by the National Basic Research Program of China (Grant No. 2013CB932804), the National Natural Science Foundation of China (Grant Nos. 91227115, 11421063, 11504431, and 21503275), the Fundamental Research Funds for Central Universities of China (Grant No. 15CX02025A), and the Application Research Foundation for Post-doctoral Scientists of Qingdao City, China (Grant No. T1404096).

Enhancement of catalytic activity of enzymes by heating in anhydrous organic solvents: 3D structure of a modified serine proteinase at high resolution.

PubMed

Sharma, S; Tyagi, R; Gupta, M N; Singh, T P

2001-01-01

For the first time, it is demonstrated that exposure of an enzyme to anhydrous organic solvents at optimized high temperature enhances its catalytic power through local changes at the binding region. Six enzymes, namely, proteinase K, wheat germ acid phosphatase, alpha-amylase, beta-glucosidase, chymotrypsin and trypsin were exposed to acetonitrile at 70 degrees C for three hr. The activities of these enzymes were found to be considerably enhanced. In order to understand the basis of this change in the activity of these enzymes, proteinase K was analyzed in detail using X-ray diffraction method. The overall structure of the enzyme was found to be similar to the native structure in aqueous environment. The hydrogen bonding system of the catalytic triad remained intact after the treatment. However, the water structure in the substrate binding site underwent some rearrangement as some of the water molecules were either displaced or completely absent. The most striking observation concerning the water structure was the complete deletion of the water molecule which occupied the position at the so-called oxyanion hole in the active site of the native enzyme. Three acetonitrile molecules were found in the present structure. All the acetonitrile molecules were located in the recognition site. Interlinked through water molecules, the sites occupied by acetonitrile molecules were independent of water molecules. The acetonitrile molecules are involved in extensive interactions with the protein atoms. The methyl group of one of the acetonitrile molecules (CCN1) interacts simultaneously with the hydrophobic side chains of Leu 96, Ile 107 and Leu 133. The development of such a hydrophobic environment at the recognition site introduced a striking conformation change in Ile 107 by rotating its side chain about C alpha-C beta bond by 180 degrees to bring about the delta-methyl group within the range of attractive van der Waals interactions with the methyl group of CCN1. A similar change had earlier been observed in proteinase K when it was complexed to a substrate analogue, lactoferrin fragment.

Effects of the internal friction and the solvent quality on the dynamics of a polymer chain closure.

PubMed

Yu, Wancheng; Luo, Kaifu

2015-03-28

Using 3D Langevin dynamics simulations, we investigate the effects of the internal friction and the solvent quality on the dynamics of a polymer chain closure. We show that the chain closure in good solvents is a purely diffusive process. By extrapolation to zero solvent viscosity, we find that the internal friction of a chain plays a non-ignorable role in the dynamics of the chain closure. When the solvent quality changes from good to poor, the mean closure time τc decreases by about 1 order of magnitude for the chain length 20 ≤ N ≤ 100. Furthermore, τc has a minimum as a function of the solvent quality. With increasing the chain length N, the minimum of τc occurs at a better solvent. Finally, the single exponential distributions of the closure time in poor solvents suggest that the negative excluded volume of segments does not alter the nearly Poisson statistical characteristics of the process of the chain closure.

Quantitative expression of protein heterogeneity: Response of amino acid side chains to their local environment.

PubMed

Bandyopadhyay, Debashree; Mehler, Ernest L

2008-08-01

A general method has been developed to characterize the hydrophobicity or hydrophilicity of the microenvironment (MENV), in which a given amino acid side chain is immersed, by calculating a quantitative property descriptor (QPD) based on the relative (to water) hydrophobicity of the MENV. Values of the QPD were calculated for a test set of 733 proteins to analyze the modulating effects on amino acid residue properties by the MENV in which they are imbedded. The QPD values and solvent accessibility were used to derive a partitioning of residues based on the MENV hydrophobicities. From this partitioning, a new hydrophobicity scale was developed, entirely in the context of protein structure, where amino acid residues are immersed in one or more "MENVpockets." Thus, the partitioning is based on the residues "sampling" a large number of "solvents" (MENVs) that represent a very large range of hydrophobicity values. It was found that the hydrophobicity of around 80% of amino acid side chains and their MENV are complementary to each other, but for about 20%, the MENV and their imbedded residue can be considered as mismatched. Many of these mismatches could be rationalized in terms of the structural stability of the protein and/or the involvement of the imbedded residue in function. The analysis also indicated a remarkable conservation of local environments around highly conserved active site residues that have similar functions across protein families, but where members have relatively low sequence homology. Thus, quantitative evaluation of this QPD is suggested, here, as a tool for structure-function prediction, analysis, and parameter development for the calculation of properties in proteins. (c) 2008 Wiley-Liss, Inc.

Development and Modeling of a Novel Self-Assembly Process for Polymer and Polymeric Composite Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sumpter, Bobby G.; Carrillo, Jan-Michael Y.; Ahn, Suk-Kyun

Extensive computational simulations and experiments have been used to investigate the structure, dynamics and resulting photophysical properties of a number para-phenylenevinylene (PPV) based polymers and oligomers. These studies have shown how the morphology and structure are controlled to a large extent by the nature of the solute-solvent interactions in the initial solution phase preparation. A good solvent such as dichloromethane generates non-compact structures with more of a defect-extended chain like morphology while a bad solvent such as toluene leads to compact organized and folded structures with rod-like morphologies. Secondary structural organization is induced by using the solution phase structures tomore » generate solvent-free single molecule nanoparticles. These nanoparticles are very compact and rod shaped, consisting of near-cofacial ordering of the conjugated PPV chain backbones between folds located at tetrahedral defects (sp3 C-C bonds). The resulting photophysical properties exhibit a significant enhancement in the photoluminescence quantum yield, lifetime, and stability. In addition, the single molecule nanoparticles have Gaussian-like emission spectra with discrete center frequencies that are correlated to a conjugation length, allowing the design of nanoparticles which luminesces at a particular frequency. We followed a similar approach and applied a comparable methodology in our recent work on polythiophenes in order to study the effect of polymer architecture on nanoscale assembly. Unlike linear chains of comparable size, we observed aggregation of the bottlebrush architecture of poly(norbornene)-g-poly(3-hexylthiophene) (PNB-g-P3HT) after the freeze-drying and dissolution processes. The behavior can be attributed to a significant enhancement in the number of π-π interactions between grafted P3HT side chains.« less

Amphiphilic polymer based on fluoroalkyl and PEG side chains for fouling release coating

NASA Astrophysics Data System (ADS)

Cong, W. W.; Wang, K.; Yu, X. Y.; Zhang, H. Q.; Lv, Z.; Gui, T. J.

2017-12-01

Under static conditions, fouling release coating could not express good release property to marine organisms. Amphiphilic polymer with mixture of fluorinated monomer and short side group of polyethylene glycol (PEG) was synthesized. And also we studied the ability of amphiphilic polymer to influence the surface properties and how it controlled the adhesion of marine organisms to coated surfaces. By incorporating fluorinated monomer and PEG side chain into the polymer, the effect of incorporating both polar and non-polar groups on fouling-release coating could be studied. The dry surface was characterized by three-dimensional digital microscopy and scanning electron microscopy (SEM), and the morphology of the amphiphilic fouling release coating showed just like flaky petal. The amphiphilic polymer in fouling release coating tended to reconstruct in water, and the ability was examined by static contact angle, which was smaller than the PDMS (polydimethylsiloxane) fouling release coating. Also surface energy was calculated by three solvents, and surface energy of amphiphilic fouling release coating was higher than that of the PDMS fouling release coating. To understand more about its fouling release property, seawater exposure method was adopted in gulf of Qingdao port. Fewer diatoms Navicula were found in biofilm after using amphiphilic fouling release coating. In general, coating containing both PEG and fluorinated side chain possessed certain fouling release property.

Bis(2-{2-[2-(benzyl­carbamo­yl)phen­oxy]acetamido}­eth­yl)ammonium nitrate ethanol disolvate

PubMed Central

Liu, Jiaji; Tang, Xiaoliang; Lu, Zhengdan; Zhang, Guolin; Liu, Weisheng

2011-01-01

In the title compound, C36H40N5O6 +·NO3 −·2C2H5OH, the nitrate anion is disordered over the two orientations of equal occupancy while the solvent mol­ecule reveals large displacement parameters. The cation is formed by protonation of the N atom of a secondary amine in the middle of the flexible chain and the whole compound has crystallographically imposed C-2 symmetry with the crystallographic b axis. An O atom of the nitrate anion links the acidic H atoms of the cation via N—H⋯O hydrogen bonding. In addition, neighbouring cations are connected by inter­molecular N—H⋯O hydrogen bonds and π–π inter­actions between the benzamide groups of the cations [centroid–centroid distance = 4.000 (3) Å], forming a chain along [001]. The ethanol solvent mol­ecules are arranged on the side of the chain through O—H⋯O hydrogen bonds. PMID:21522705

Adapting Poisson-Boltzmann to the self-consistent mean field theory: Application to protein side-chain modeling

NASA Astrophysics Data System (ADS)

Koehl, Patrice; Orland, Henri; Delarue, Marc

2011-08-01

We present an extension of the self-consistent mean field theory for protein side-chain modeling in which solvation effects are included based on the Poisson-Boltzmann (PB) theory. In this approach, the protein is represented with multiple copies of its side chains. Each copy is assigned a weight that is refined iteratively based on the mean field energy generated by the rest of the protein, until self-consistency is reached. At each cycle, the variational free energy of the multi-copy system is computed; this free energy includes the internal energy of the protein that accounts for vdW and electrostatics interactions and a solvation free energy term that is computed using the PB equation. The method converges in only a few cycles and takes only minutes of central processing unit time on a commodity personal computer. The predicted conformation of each residue is then set to be its copy with the highest weight after convergence. We have tested this method on a database of hundred highly refined NMR structures to circumvent the problems of crystal packing inherent to x-ray structures. The use of the PB-derived solvation free energy significantly improves prediction accuracy for surface side chains. For example, the prediction accuracies for χ1 for surface cysteine, serine, and threonine residues improve from 68%, 35%, and 43% to 80%, 53%, and 57%, respectively. A comparison with other side-chain prediction algorithms demonstrates that our approach is consistently better in predicting the conformations of exposed side chains.

Structure of the ordered hydration of amino acids in proteins: analysis of crystal structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biedermannová, Lada, E-mail: lada.biedermannova@ibt.cas.cz; Schneider, Bohdan

2015-10-27

The hydration of protein crystal structures was studied at the level of individual amino acids. The dependence of the number of water molecules and their preferred spatial localization on various parameters, such as solvent accessibility, secondary structure and side-chain conformation, was determined. Crystallography provides unique information about the arrangement of water molecules near protein surfaces. Using a nonredundant set of 2818 protein crystal structures with a resolution of better than 1.8 Å, the extent and structure of the hydration shell of all 20 standard amino-acid residues were analyzed as function of the residue conformation, secondary structure and solvent accessibility. Themore » results show how hydration depends on the amino-acid conformation and the environment in which it occurs. After conformational clustering of individual residues, the density distribution of water molecules was compiled and the preferred hydration sites were determined as maxima in the pseudo-electron-density representation of water distributions. Many hydration sites interact with both main-chain and side-chain amino-acid atoms, and several occurrences of hydration sites with less canonical contacts, such as carbon–donor hydrogen bonds, OH–π interactions and off-plane interactions with aromatic heteroatoms, are also reported. Information about the location and relative importance of the empirically determined preferred hydration sites in proteins has applications in improving the current methods of hydration-site prediction in molecular replacement, ab initio protein structure prediction and the set-up of molecular-dynamics simulations.« less

Applying Thienyl Side Chains and Different π-Bridge to Aromatic Side-Chain Substituted Indacenodithiophene-Based Small Molecule Donors for High-Performance Organic Solar Cells.

PubMed

Wang, Jin-Liang; Liu, Kai-Kai; Liu, Sha; Liu, Feng; Wu, Hong-Bin; Cao, Yong; Russell, Thomas P

2017-06-14

A pair of linear tetrafluorinated small molecular donors, named as ThIDTTh4F and ThIDTSe4F, which are with tetrathienyl-substituted IDT as electron-rich central core, electron-deficient difluorobenzothiadiazole as acceptor units, and donor end-capping groups, but having differences in the π-bridge (thiophene and selenophene), were successfully synthesized and evaluated as donor materials in organic solar cells. Such π-bridge and core units in these small molecules play a decisive role in the formation of the nanoscale separation of the blend films, which were systematically investigated through absorption spectra, grazing incidence X-ray diffraction pattern, transmission electron microscopy images, resonant soft X-ray scattering profiles, and charge mobility measurement. The ThIDTSe4F (with selenophene π-bridge)-based device exhibited superior performance than devices based on ThIDTh4F (with thiophene π-bridge) after post annealing treatment owing to optimized film morphology and improved charge transport. Power conversion efficiency of 7.31% and fill factor of ∼0.70 were obtained by using a blend of ThIDTSe4F and PC 71 BM with thermal annealing and solvent vapor annealing treatments, which is the highest PCE from aromatic side-chain substituted IDT-based small molecular solar cells. The scope of this study is to reveal the structure-property relationship of the aromatic side-chain substituted IDT-based donor materials as a function of π-bridge and the post annealing conditions.

Simultaneous tuning of chemical composition and topography of copolymer surfaces: micelles as building blocks.

PubMed

Zhao, Ning; Zhang, Xiaoyan; Zhang, Xiaoli; Xu, Jian

2007-05-14

A simple method is described for controlling the surface chemical composition and topography of the diblock copolymer poly(styrene)-b-poly(dimethylsiloxane)(PS-b-PDMS) by casting the copolymer solutions from solvents with different selectivities. The surface morphology and chemical composition were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), respectively, and the wetting behavior was studied by water contact angle (CA) and sliding angle (SA) and by CA hysteresis. Chemical composition and morphology of the surface depend on solvent properties, humidity of the air, solution concentration, and block lengths. If the copolymer is cast from a common solvent, the resultant surface is hydrophobic, with a flat morphology, and dominated by PDMS on the air side. From a PDMS-selective solvent, the surface topography depends on the morphology of the micelles. Starlike micelles give rise to a featureless surface nearly completely covered by PDMS, while crew-cut-like micelles lead to a rough surface with a hierarchical structure that consists partly of PDMS. From a PS-selective solvent, however, surface segregation of PDMS was restricted, and the surface morphology can be controlled by vapor-induced phase separation. On the basis of the tunable surface roughness and PDMS concentration on the air side, water repellency of the copolymer surface could be tailored from hydrophobic to superhydrophobic. In addition, reversible switching behavior between hydrophobic and superhydrophobic can be achieved by exposing the surface to solvents with different selectivities.

Structure and energetics of model amphiphilic molecules at the water liquid-vapor interface - A molecular dynamics study

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; Benjamin, Ilan

1993-01-01

A molecular dynamics study of adsorption of p-n-pentylphenol at infinite dilution at the water liquid-vapor interface is reported. The calculated free energy of adsorption is -8.8 +/- 0.7 kcal/mol, in good agreement with the experimental value of -7.3 kcal/mol. The transition between the interfacial region and the bulk solution is sharp and well-defined by energetic, conformational, and orientational criteria. At the water surface, the phenol head group is mostly immersed in aqueous solvent. The most frequent orientation of the hydrocarbon tail is parallel to the interface, due to dispersion interactions with the water surface. This arrangement of the phenol ring and the alkyl chain requires that the chain exhibits a kink. As the polar head group is being moved into the solvent, the chain length increases and the tail becomes increasingly aligned toward the surface normal, such that the nonpolar part of the molecule exposed to water is minimized. The same effect was achieved when phenol was replaced by a more polar head group, phenolate.

Advancements and Application of Microsecond Synchrotron X-ray Footprinting at the Advanced Light Source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Sayan; Celestre, Rich; Feng, Jun

2016-01-02

The method of synchrotron X-ray protein footprinting (XF-MS) is used to determine protein conformational changes, folding, protein-protein and protein-ligand interactions, providing information which is often difficult to obtain using X-ray crystallography and other common structural biology methods [1 G. Xu and M.R. Chance, Chemical Reviews 107, 3514–3543 (2007). [CrossRef], [PubMed], [Web of Science ®], [Google Scholar] –3 V.N. Bavro, Biochem Soc Trans 43, 983–994 (2015). [CrossRef], [PubMed], [Web of Science ®], [Google Scholar] ]. The technique uses comparative in situ labeling of solvent-accessible side chains by highly reactive hydroxyl radicals (•OH) in buffered aqueous solution under different assay conditions. Inmore » regions where a protein is folded or binds a partner, these •OH susceptible sites are inaccessible to solvent, and therefore protected from labeling. The •OH are generated by the ionization of water using high-flux-density X-rays. High-flux density is a key factor for XF-MS labeling because obtaining an adequate steady-state concentration of hydroxyl radical within a short irradiation time is necessary to minimize radiation-induced secondary damage and also to overcome various scavenging reactions that reduce the yield of labeled side chains.« less

Copolymer Synthesis and Characterization by Post-Polymerization Modification

NASA Astrophysics Data System (ADS)

Galvin, Casey James

This PhD thesis examines the physical behavior of surface-grafted polymer assemblies (SGPAs) derived from post-polymerization modification (PPM) reactions in aqueous and vapor enriched environments, and offers an alternative method of creating SGPAs using a PPM approach. SGPAs comprise typically polymer chains grafted covalently to solid substrates. These assemblies show promise in a number of applications and technologies due to the stability imparted by the covalent graft and ability to modify interfacial properties and stability. SGPAs also offer a set of rich physics to explore in fundamental investigations as a result of confining macromolecules to a solid substrate. PPM reactions (also called polymer analogous reactions) apply small molecule organic chemistry reactions to the repeat units of polymer chains in order to generate new chemistries. By applying a PPM strategy to SGPAs, a wide variety of functional groups can be introduced into a small number of well-studied and well-behaved model polymer systems. This approach offers the advantage of holding constant other properties of the SGPA (e.g., molecular weight, MW, and grafting density, sigma) to isolate the effect of chemistry on physical behavior. Using a combination of PPM and fabrication methods that facilitate the formation of SPGAs with position-dependent gradual variation of sigma on flat impenetrable substrate, the influence of polymer chemistry and sigma is examined on the stability of weak polyelectrolyte brushes in aqueous environments at different pH levels. Degrafting of polymer chains in SGPAs exhibits a complex dependence on side chain chemistry, sigma, pH and the charge fraction (alpha) within the brush. Results of these experiments support a proposed mechanism of degrafting, wherein extension of the grafted chains away from the substrate generates tension along the polymer backbone, which activates the grafting chemistry for hydrolysis. The implications of these findings are important in developing technologies that use SGPAs in aqueous environments, and point to a need for potential alternative grafting chemistries. The behavior of SGPAs in vapor environments remains an underexplored phenomenon. By changing systematically the chemistry of SGPAs derived from a parent sample, the influence of side chain functional groups on the swelling of weak and strong polyelectrolyte brushes in the presence of water, methanol and ethanol vapors is explored. The extent of swelling and solvent uptake depends strongly on the chemistry in the polymer side chain and of the solvent. Despite bearing a permanent electrostatic charge in the side chain, the strong polyelectrolyte brushes exhibit no behavior typical of polyelectrolytes in water due to no dissociation of the counterion. Of particular interest is the behavior in humid environments of an SGPA bearing a zwitterionic group in its side chain, which results in exposure of electrostatic charges without counterions. Using substrates bearing the aforementioned sigma gradient of polymeric grafts, evidence of inter- and intramolecular complex formation is presented. Finally, a method of developing SGPAs by polymerizing bulk polymer chains through surface-grafted monomers (SGMs) is described. The SGMs are incorporated onto a solid substrate using the same PPM reaction employed in the degrafting and vapor swelling experiments, highlighting the versatility of PPM. The thickness of these SGPAs is correlated to the bulk polymer chains MW, suggesting this technique can be used in existing industrial bulk polymerization processes.

The Mechanism by Which Arabinoxylanases Can Recognize Highly Decorated Xylans*

PubMed Central

Labourel, Aurore; Crouch, Lucy I.; Brás, Joana L. A.; Jackson, Adam; Rogowski, Artur; Gray, Joseph; Yadav, Madhav P.; Henrissat, Bernard; Fontes, Carlos M. G. A.; Gilbert, Harry J.; Najmudin, Shabir; Baslé, Arnaud; Cuskin, Fiona

2016-01-01

The enzymatic degradation of plant cell walls is an important biological process of increasing environmental and industrial significance. Xylan, a major component of the plant cell wall, consists of a backbone of β-1,4-xylose (Xylp) units that are often decorated with arabinofuranose (Araf) side chains. A large penta-modular enzyme, CtXyl5A, was shown previously to specifically target arabinoxylans. The mechanism of substrate recognition displayed by the enzyme, however, remains unclear. Here we report the crystal structure of the arabinoxylanase and the enzyme in complex with ligands. The data showed that four of the protein modules adopt a rigid structure, which stabilizes the catalytic domain. The C-terminal non-catalytic carbohydrate binding module could not be observed in the crystal structure, suggesting positional flexibility. The structure of the enzyme in complex with Xylp-β-1,4-Xylp-β-1,4-Xylp-[α-1,3-Araf]-β-1,4-Xylp showed that the Araf decoration linked O3 to the xylose in the active site is located in the pocket (−2* subsite) that abuts onto the catalytic center. The −2* subsite can also bind to Xylp and Arap, explaining why the enzyme can utilize xylose and arabinose as specificity determinants. Alanine substitution of Glu68, Tyr92, or Asn139, which interact with arabinose and xylose side chains at the −2* subsite, abrogates catalytic activity. Distal to the active site, the xylan backbone makes limited apolar contacts with the enzyme, and the hydroxyls are solvent-exposed. This explains why CtXyl5A is capable of hydrolyzing xylans that are extensively decorated and that are recalcitrant to classic endo-xylanase attack. PMID:27531750

Ultrafast Hydration Dynamics and Coupled Water-Protein Fluctuations in Apomyoglobin

NASA Astrophysics Data System (ADS)

Yang, Yi; Zhang, Luyuan; Wang, Lijuan; Zhong, Dongping

2009-06-01

Protein hydration dynamics are of fundamental importance to its structure and function. Here, we characterize the global solvation dynamics and anisotropy dynamics around the apomyoglobin surface in different conformational states (native and molten globule) by measuring the Stokes shift and anisotropy decay of tryptophan with femtosecond-resolved fluorescence upconversion. With site-directed mutagenesis, we designed sixteen mutants with one tryptophan in each, and placed the probe at a desirable position ranging from buried in the protein core to fully solvent-exposed on the protein surface. In all protein sites studied, two distinct solvation relaxations (1-8 ps and 20-200 ps) were observed, reflecting the initial collective water relaxation and subsequent hydrogen-bond network restructuring, respectively, and both are strongly correlated with protein's local structures and chemical properties. The hydration dynamics of the mutants in molten globule state are faster than those observed in native state, indicating that the protein becomes more flexible and less structured when its conformation is converted from fully-folded native state to partially-folded molten globule state. Complementary, fluorescence anisotropy dynamics of all mutants in native state show an increasing trend of wobbling times (40-260 ps) when the location of the probe is changed from a loop, to a lateral helix, and then, to the compact protein core. Such an increase in wobbling times is related to the local protein structural rigidity, which relates the interaction of water with side chains. The ultrafast hydration dynamics and related side-chain motion around the protein surface unravel the coupled water-protein fluctuations on the picosecond time scales and indicate that the local protein motions are slaved by hydrating water fluctuations.

Interaction of anesthetic molecules with α-helix and polyproline II extended helix of long-chain poly-L-lysine

NASA Astrophysics Data System (ADS)

Cieślik-Boczula, Katarzyna; Rospenk, Maria

2018-01-01

The effect of halothane, enflurane, sevoflurane, and isoflurane molecules, as volatile anesthetics, on the α-helices and polyproline II extended helices (PPII) of long-chain poly-L-lysine (PLL) were studied using Fourier-transform infrared and vibrational circular dichroism spectroscopy. Uncharged and charged α-helices, as well as charged extended PPII helices, were subjected to anesthetic actions in solvents with different pD values or methanol to water ratios. A crucial factor responsible for hindering the anesthetic-PLL interactions is shown to be the ionization of amino groups of the PLL side chains. The α-helix to β-sheet transition was triggered only for the uncharged α-helical structures of PLL by the nonpolar anesthetics under study.

Determination of protein folding kinetic types using sequence and predicted secondary structure and solvent accessibility.

PubMed

Zhang, Hua; Zhang, Tuo; Gao, Jianzhao; Ruan, Jishou; Shen, Shiyi; Kurgan, Lukasz

2012-01-01

Proteins fold through a two-state (TS), with no visible intermediates, or a multi-state (MS), via at least one intermediate, process. We analyze sequence-derived factors that determine folding types by introducing a novel sequence-based folding type predictor called FOKIT. This method implements a logistic regression model with six input features which hybridize information concerning amino acid composition and predicted secondary structure and solvent accessibility. FOKIT provides predictions with average Matthews correlation coefficient (MCC) between 0.58 and 0.91 measured using out-of-sample tests on four benchmark datasets. These results are shown to be competitive or better than results of four modern predictors. We also show that FOKIT outperforms these methods when predicting chains that share low similarity with the chains used to build the model, which is an important advantage given the limited number of annotated chains. We demonstrate that inclusion of solvent accessibility helps in discrimination of the folding kinetic types and that three of the features constitute statistically significant markers that differentiate TS and MS folders. We found that the increased content of exposed Trp and buried Leu are indicative of the MS folding, which implies that the exposure/burial of certain hydrophobic residues may play important role in the formation of the folding intermediates. Our conclusions are supported by two case studies.

A comprehensive search for calcium binding sites critical for TMEM16A calcium-activated chloride channel activity

PubMed Central

Tien, Jason; Peters, Christian J; Wong, Xiu Ming; Cheng, Tong; Jan, Yuh Nung; Jan, Lily Yeh; Yang, Huanghe

2014-01-01

TMEM16A forms calcium-activated chloride channels (CaCCs) that regulate physiological processes such as the secretions of airway epithelia and exocrine glands, the contraction of smooth muscles, and the excitability of neurons. Notwithstanding intense interest in the mechanism behind TMEM16A-CaCC calcium-dependent gating, comprehensive surveys to identify and characterize potential calcium sensors of this channel are still lacking. By aligning distantly related calcium-activated ion channels in the TMEM16 family and conducting systematic mutagenesis of all conserved acidic residues thought to be exposed to the cytoplasm, we identify four acidic amino acids as putative calcium-binding residues. Alterations of the charge, polarity, and size of amino acid side chains at these sites alter the ability of different divalent cations to activate the channel. Furthermore, TMEM16A mutant channels containing double cysteine substitutions at these residues are sensitive to the redox potential of the internal solution, providing evidence for their physical proximity and solvent accessibility. DOI: http://dx.doi.org/10.7554/eLife.02772.001 PMID:24980701

Design and characterization of the anion-sensitive coiled-coil peptide.

PubMed Central

Hoshino, M.; Yumoto, N.; Yoshikawa, S.; Goto, Y.

1997-01-01

As a model for analyzing the role of charge repulsion in proteins and its shielding by the solvent, we designed a peptide of 27 amino acid residues that formed a homodimeric coiled-coil. The interface between the coils consisted of hydrophobic Leu and Val residues, and 10 Lys residues per monomer were incorporated into the positions exposed to solvent. During the preparation of a disulfide-linked dimer in which the two peptides were linked in parallel by the two disulfide bonds located at the N and C terminals, a cyclic monomer with an intramolecular disulfide bond was also obtained. On the basis of CD and 1H-NMR, the conformational stabilities of these isomers and several reference peptides were examined. Whereas all these peptides were unfolded in the absence of salt at pH 4.7 and 20 degrees C, the addition of NaClO4 cooperatively stabilized the alpha-helical conformation. The crosslinking of the peptides by disulfide bonds significantly decreased the midpoint salt concentration of the transition. The 1H-NMR spectra in the presence of NaClO4 suggested that, whereas the disulfide-bonded dimer assumed a native-like conformation, the cyclic monomer assumed a molten globule-like conformation with disordered side chains. However, the cyclic monomer exhibited cooperative transitions against temperature and Gdn-HCl that were only slightly less cooperative than those of the disulfide-bonded parallel dimer. These results indicate that the charge repulsion critically destabilizes the native-like state as well as the molten globule-like state, and that the solvent-dependent charge repulsion may be useful for controlling the conformation of designed peptides. PMID:9232640

Folding and stability of helical bundle proteins from coarse-grained models.

PubMed

Kapoor, Abhijeet; Travesset, Alex

2013-07-01

We develop a coarse-grained model where solvent is considered implicitly, electrostatics are included as short-range interactions, and side-chains are coarse-grained to a single bead. The model depends on three main parameters: hydrophobic, electrostatic, and side-chain hydrogen bond strength. The parameters are determined by considering three level of approximations and characterizing the folding for three selected proteins (training set). Nine additional proteins (containing up to 126 residues) as well as mutated versions (test set) are folded with the given parameters. In all folding simulations, the initial state is a random coil configuration. Besides the native state, some proteins fold into an additional state differing in the topology (structure of the helical bundle). We discuss the stability of the native states, and compare the dynamics of our model to all atom molecular dynamics simulations as well as some general properties on the interactions governing folding dynamics. Copyright © 2013 Wiley Periodicals, Inc.

Two-photon absorption of [2.2]paracyclophane derivatives in solution: A theoretical investigation

NASA Astrophysics Data System (ADS)

Ferrighi, Lara; Frediani, Luca; Fossgaard, Eirik; Ruud, Kenneth

2007-12-01

The two-photon absorption of a class of [2.2]paracyclophane derivatives has been studied using quadratic response and density functional theories. For the molecules investigated, several effects influencing the two-photon absorption spectra have been investigated, such as side-chain elongation, hydrogen bonding, the use of ionic species, and solvent effects, the latter described by the polarizable continuum model. The calculations have been carried out using a recent parallel implementation of the polarizable continuum model in the DALTON code. Special attention is given to those aspects that could explain the large solvent effect on the two-photon absorption cross sections observed experimentally for this class of compounds.

Comparison of polymer induced and solvent induced trypsin denaturation: the role of hydrophobicity.

PubMed

Jasti, Lakshmi S; Fadnavis, Nitin W; Addepally, Uma; Daniels, Siona; Deokar, Sarika; Ponrathnam, Surendra

2014-04-01

Trypsin adsorption from aqueous buffer by various copolymers of allyl glycidyl ether-ethylene glycol dimethacrylate (AGE-EGDM) copolymer with varying crosslink density increases with increasing crosslink density and the effect slowly wears off after reaching a plateau at 50% crosslink density. The copolymer with 25% crosslink density was reacted with different amines with alkyl/aryl side chains to obtain a series of copolymers with 1,2-amino alcohol functional groups and varying hydrophobicity. Trypsin binding capacity again increases with hydrophobicity of the reacting amine and a good correlation between logPoctanol of the amine and protein binding is observed. The bound trypsin is denatured to the extent of 90% in spite of the presence of hydrophilic hydroxyl and amino groups. The behavior was comparable to that in mixtures of aqueous buffer and water-miscible organic co-solvents where the solvent concentration required to deactivate 50% of the enzyme (C50) is dependent on logPoctanol of the co-solvent. Copyright © 2014 Elsevier B.V. All rights reserved.

Thermodynamic Effects of Noncoded and Coded Methionine Substitutions in Calmodulin

PubMed Central

Yamniuk, Aaron P.; Ishida, Hiroaki; Lippert, Dustin; Vogel, Hans J.

2009-01-01

The methionine residues in the calcium (Ca2+) regulatory protein calmodulin (CaM) are structurally and functionally important. They are buried within the N- and C-domains of apo-CaM but become solvent-exposed in Ca2+-CaM, where they interact with numerous target proteins. Previous structural studies have shown that methionine substitutions to the noncoded amino acids selenomethionine, ethionine, or norleucine, or mutation to leucine do not impact the main chain structure of CaM. Here we used differential scanning calorimetry to show that these substitutions enhance the stability of both domains, with the largest increase in melting temperature (19–26°C) achieved with leucine or norleucine in the apo-C-domain. Nuclear magnetic resonance spectroscopy experiments also revealed the loss of a slow conformational exchange process in the Leu-substituted apo-C-domain. In addition, isothermal titration calorimetry experiments revealed considerable changes in the enthalpy and entropy of target binding to apo-CaM and Ca2+-CaM, but the free energy of binding was largely unaffected due to enthalpy-entropy compensation. Collectively, these results demonstrate that noncoded and coded methionine substitutions can be accommodated in CaM because of the structural plasticity of the protein. However, adjustments in side-chain packing and dynamics lead to significant differences in protein stability and the thermodynamics of target binding. PMID:19217866

Central auditory processing effects induced by solvent exposure.

PubMed

Fuente, Adrian; McPherson, Bradley

2007-01-01

Various studies have demonstrated that organic solvent exposure may induce auditory damage. Studies conducted in workers occupationally exposed to solvents suggest, on the one hand, poorer hearing thresholds than in matched non-exposed workers, and on the other hand, central auditory damage due to solvent exposure. Taking into account the potential auditory damage induced by solvent exposure due to the neurotoxic properties of such substances, the present research aimed at studying the possible auditory processing disorder (APD), and possible hearing difficulties in daily life listening situations that solvent-exposed workers may acquire. Fifty workers exposed to a mixture of organic solvents (xylene, toluene, methyl ethyl ketone) and 50 non-exposed workers matched by age, gender and education were assessed. Only subjects with no history of ear infections, high blood pressure, kidney failure, metabolic and neurological diseases, or alcoholism were selected. The subjects had either normal hearing or sensorineural hearing loss, and normal tympanometric results. Hearing-in-noise (HINT), dichotic digit (DD), filtered speech (FS), pitch pattern sequence (PPS), and random gap detection (RGD) tests were carried out in the exposed and non-exposed groups. A self-report inventory of each subject's performance in daily life listening situations, the Amsterdam Inventory for Auditory Disability and Handicap, was also administered. Significant threshold differences between exposed and non-exposed workers were found at some of the hearing test frequencies, for both ears. However, exposed workers still presented normal hearing thresholds as a group (equal or better than 20 dB HL). Also, for the HINT, DD, PPS, FS and RGD tests, non-exposed workers obtained better results than exposed workers. Finally, solvent-exposed workers reported significantly more hearing complaints in daily life listening situations than non-exposed workers. It is concluded that subjects exposed to solvents may acquire an APD and thus the sole use of pure-tone audiometry is insufficient to assess hearing in solvent-exposed populations.

Softening of the stiffness of bottle-brush polymers by mutual interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bolisetty, S.; Airaud, C.; Rosenfeldt, S.

2007-04-15

We study bottle-brush macromolecules in a good solvent by small-angle neutron scattering (SANS), static light scattering (SLS), and dynamic light scattering (DLS). These polymers consist of a linear backbone to which long side chains are chemically grafted. The backbone contains about 1600 monomer units (weight average) and every second monomer unit carries side chains with approximately 60 monomer units. The SLS and SANS data extrapolated to infinite dilution lead to the form factor of the polymer that can be described in terms of a wormlike chain with a contour length of 380 nm and a persistence length of 17.5 nm.more » An analysis of the DLS data confirms these model parameters. The scattering intensities taken at finite concentration can be modeled using the polymer reference interaction site model. It reveals a softening of the bottle-brush polymers caused by their mutual interaction. We demonstrate that the persistence decreases from 17.5 nm down to 5 nm upon increasing the concentration from dilute solution to the highest concentration (40.59 g/l) under consideration. The observed softening of the chains is comparable to the theoretically predicted decrease of the electrostatic persistence length of linear polyelectrolyte chains at finite concentrations.« less

Modeling side-chains using molecular dynamics improve recognition of binding region in CAPRI targets.

PubMed

Camacho, Carlos J

2005-08-01

The CAPRI-II experiment added an extra level of complexity to the problem of predicting protein-protein interactions by including 5 targets for which participants had to build or complete the 3-dimensional (3D) structure of either the receptor or ligand based on the structure of a close homolog. In this article, we describe how modeling key side-chains using molecular dynamics (MD) in explicit solvent improved the recognition of the binding region of a free energy- based computational docking method. In particular, we show that MD is able to predict with relatively high accuracy the rotamer conformation of the anchor side-chains important for molecular recognition as suggested by Rajamani et al. (Proc Natl Acad Sci USA 2004;101:11287-11292). As expected, the conformations are some of the most common rotamers for the given residue, while latch side-chains that undergo induced fit upon binding are forced into less common conformations. Using these models as starting conformations in conjunction with the rigid-body docking server ClusPro and the flexible docking algorithm SmoothDock, we produced valuable predictions for 6 of the 9 targets in CAPRI-II, missing only the 3 targets that underwent significant structural rearrangements upon binding. We also show that our free energy- based scoring function, consisting of the sum of van der Waals, Coulombic electrostatic with a distance-dependent dielectric, and desolvation free energy successfully discriminates the nativelike conformation of our submitted predictions. The latter emphasizes the critical role that thermodynamics plays on our methodology, and validates the generality of the algorithm to predict protein interactions.

O2 and Water Migration Pathways between the Solvent and Heme Pockets of Hemoglobin with Open and Closed Conformations of the Distal HisE7.

PubMed

Shadrina, Maria S; Peslherbe, Gilles H; English, Ann M

2015-09-01

Hemoglobin transports O2 by binding the gas at its four hemes. Hydrogen bonding between the distal histidine (HisE7) and heme-bound O2 significantly increases the affinity of human hemoglobin (HbA) for this ligand. HisE7 is also proposed to regulate the release of O2 to the solvent via a transient E7 channel. To reveal the O2 escape routes controlled by HisE7 and to evaluate its role in gating heme access, we compare simulations of O2 diffusion from the distal heme pockets of the T and R states of HbA performed with HisE7 in its open (protonated) and closed (neutral) conformations. Irrespective of HisE7's conformation, we observe the same four or five escape routes leading directly from the α- or β-distal heme pockets to the solvent. Only 21-53% of O2 escapes occur via these routes, with the remainder escaping through routes that encompass multiple internal cavities in HbA. The conformation of the distal HisE7 controls the escape of O2 from the heme by altering the distal pocket architecture in a pH-dependent manner, not by gating the E7 channel. Removal of the HisE7 side chain in the GlyE7 variant exposes the distal pockets to the solvent, and the percentage of O2 escapes to the solvent directly from the α- or β-distal pockets of the mutant increases to 70-88%. In contrast to O2, the dominant water route from the bulk solvent is gated by HisE7 because protonation and opening of this residue dramatically increase the rate of influx of water into the empty distal heme pockets. The occupancy of the distal heme site by a water molecule, which functions as an additional nonprotein barrier to binding of the ligand to the heme, is also controlled by HisE7. Overall, analysis of gas and water diffusion routes in the subunits of HbA and its GlyE7 variant sheds light on the contribution of distal HisE7 in controlling polar and nonpolar ligand movement between the solvent and the hemes.

Thermodynamic description of cellulose chain collapse using coarse grain modeling

NASA Astrophysics Data System (ADS)

Das, Ritankar; Chu, Jhih-Wei

2012-11-01

Biomass contains abundant amounts of cellulose as crystalline microfibrils. A limiting step to using cellulose as an alternative energy source, however, is the hydrolysis of the biomass and subsequent transformation into fuels. Cellulose is insoluble in most solvents including organic solvents and water, but it is soluble in some ionic liquids like BMIM-Cl. This project aims to find alternative solvents that are less expensive and are more environmentally benign than the ionic liquids. All-atom molecular dynamics simulations were performed on dissociated glucan chains separated by multiple (4-5) solvation shells, in the presence of several novel solvents and solvent mixtures. The solubility of the chains in each solvent was indicated by contacts calculations after the equilibration of the molecular dynamics. It was discovered that pyridine and imidazole acted as the best solvents because their aromatic electronic structure was able to effectively disrupt the inter-sheet interactions among the glucan chains in the axial direction, and because perturbation of the solvent interactions in the presence of glucan chains was minimal.

Hydrogen Bond Networks and Hydrophobic Effects in the Amyloid β30-35 Chain in Water: A Molecular Dynamics Study.

PubMed

Jong, KwangHyok; Grisanti, Luca; Hassanali, Ali

2017-07-24

We have studied the conformational landscape of the C-terminal fragment of the amyloid protein Aβ 30-35 in water using well-tempered metadynamics simulations and found that it resembles an intrinsically disordered protein. The conformational fluctuations of the protein are facilitated by a collective reorganization of both protein and water hydrogen bond networks, combined with electrostatic interactions between termini as well as hydrophobic interactions of the side chains. The stabilization of hydrophobic interactions in one of the conformers involves a collective collapse of the side chains along with a squeeze-out of water sandwiched between them. The charged N- and C-termini play a critical role in stabilizing different types of protein conformations, including those involving contact-ion salt bridges as well as solvent-mediated interactions of the termini and the amide backbone. We have examined this by probing the distribution of directed water wires forming the hydrogen bond network enveloping the polypeptide. Water wires and their fluctuations form an integral part of structural signature of the protein conformation.

Effect of gel formation on the dissolution behavior of clarithromycin tablets.

PubMed

Inukai, Koki; Takiyama, Kei; Noguchi, Shuji; Iwao, Yasunori; Itai, Shigeru

2017-04-15

Clarithromycin (CAM) is a macrolide antibiotic that is widely used at clinical sites. We found that release of CAM is suppressed when tablets of CAM were exposed to an external solvent containing carboxylate buffers such as citrate. The suppressed release of CAM can be attributed to the formation of gels on the tablet surfaces, which inhibits penetration of the solvent into the tablet and thus disintegration of the tablets. Delayed disintegration of the tablets was also observed for commercial tablets. This suggests that taking CAM and carboxylates at the same time might be avoided. The crystal structure of CAM citrate reveals that molecular chains of CAM are cross-linked by hydrogen bond between citrate groups in the crystal. The crystal structure indicates that cross-linked CAM chains of the three-dimensional mesh structure might also be formed in high concentration CAM solutions in the presence of carboxylates, resulting in gel formation. Copyright © 2017 Elsevier B.V. All rights reserved.

Towards ultra-fast solvent evaporation, the development of a computer controlled solvent vapor annealing chamber

NASA Astrophysics Data System (ADS)

Nelson, Gunnar; Wong, J.; Drapes, C.; Grant, M.; Baruth, A.

Despite the promise of cheap and fast nanoscale ordering of block polymer thin films via solvent vapor annealing, a standardized, scalable production scheme remains elusive. Solvent vapor annealing exposes a nano-thin film to the vapors of one or more solvents with the goal of forming a swollen and mobile state to direct the self-assembly process by tuning surface energies and mediating unfavorable chain interactions. We have shown that optimized annealing conditions, where kinetic and thermal properties for crystal growth are extremely fast (<1s), exist at solvent concentrations just below the order-disorder transition of the film. However, when investigating the propagation of a given morphology into the bulk of a film during drying, the role of solvent evaporation comes under great scrutiny. During this process, the film undergoes a competition between two fronts; phase separation and kinetic trapping. Recent results in both theory and experiment point toward this critical element in controlling the resultant morphologies; however, no current method includes a controllable solvent evaporation rate at ultra-fast time scales. We report on a computer-controlled, pneumatically actuated chamber that provides control over solvent evaporation down to 15 ms. Furthermore, in situ spectral reflectance monitors solvent concentration with 10 ms temporal resolution and reveals several possible evaporation trajectories, ranging from linear to exponential to logarithmic. Funded by Dr. Randolph Ferlic Summer Research Scholarship and NASA Nebraska Space Grant.

Hydrophobic potential of mean force as a solvation function for protein structure prediction.

PubMed

Lin, Matthew S; Fawzi, Nicolas Lux; Head-Gordon, Teresa

2007-06-01

We have developed a solvation function that combines a Generalized Born model for polarization of protein charge by the high dielectric solvent, with a hydrophobic potential of mean force (HPMF) as a model for hydrophobic interaction, to aid in the discrimination of native structures from other misfolded states in protein structure prediction. We find that our energy function outperforms other reported scoring functions in terms of correct native ranking for 91% of proteins and low Z scores for a variety of decoy sets, including the challenging Rosetta decoys. This work shows that the stabilizing effect of hydrophobic exposure to aqueous solvent that defines the HPMF hydration physics is an apparent improvement over solvent-accessible surface area models that penalize hydrophobic exposure. Decoys generated by thermal sampling around the native-state basin reveal a potentially important role for side-chain entropy in the future development of even more accurate free energy surfaces.

Gamma radiation effects on siloxane-based additive manufactured structures

NASA Astrophysics Data System (ADS)

Schmalzer, Andrew M.; Cady, Carl M.; Geller, Drew; Ortiz-Acosta, Denisse; Zocco, Adam T.; Stull, Jamie; Labouriau, Andrea

2017-01-01

Siloxane-basedadditive manufactured structures prepared by the direct ink write (DIW) technology were exposed to ionizing irradiation in order to gauge radiolysis effects on structure-property relationships. These well-defined 3-D structures were subjected to moderate doses of gamma irradiation in an inert atmosphere and characterized by a suite of experimental methods. Changes in thermal, chemical, microstructure, and mechanical properties were evaluated by DSC, TGA, FT-IR, mass spectroscopy, EPR, solvent swelling, SEM, and uniaxial compressive load techniques. Our results demonstrated that 3-D structures made from aromatic-free siloxane resins exhibited hardening after being exposed to gamma radiation. This effect was accompanied by gas evolution, decreasing in crystallization levels, decreasing in solvent swelling and damage to the microstructure. Furthermore, long-lived radiation-induced radicals were not detected by EPR methods. Our results are consistent with cross-link formation being the dominant degradation mechanism over chain scission reactions. On the other hand, 3-D structures made from high phenyl content siloxane resins showed little radiation damage as evidenced by low off gassing.

Flory-type theories of polymer chains under different external stimuli

NASA Astrophysics Data System (ADS)

Budkov, Yu A.; Kiselev, M. G.

2018-01-01

In this Review, we present a critical analysis of various applications of the Flory-type theories to a theoretical description of the conformational behavior of single polymer chains in dilute polymer solutions under a few external stimuli. Different theoretical models of flexible polymer chains in the supercritical fluid are discussed and analysed. Different points of view on the conformational behavior of the polymer chain near the liquid-gas transition critical point of the solvent are presented. A theoretical description of the co-solvent-induced coil-globule transitions within the implicit-solvent-explicit-co-solvent models is discussed. Several explicit-solvent-explicit-co-solvent theoretical models of the coil-to-globule-to-coil transition of the polymer chain in a mixture of good solvents (co-nonsolvency) are analysed and compared with each other. Finally, a new theoretical model of the conformational behavior of the dielectric polymer chain under the external constant electric field in the dilute polymer solution with an explicit account for the many-body dipole correlations is discussed. The polymer chain collapse induced by many-body dipole correlations of monomers in the context of statistical thermodynamics of dielectric polymers is analysed.

Enhancement of catalytic efficiency of enzymes through exposure to anhydrous organic solvent at 70 degrees C. Three-dimensional structure of a treated serine proteinase at 2.2 A resolution.

PubMed

Gupta, M N; Tyagi, R; Sharma, S; Karthikeyan, S; Singh, T P

2000-05-15

The enzyme behavior in anhydrous media has important applications in biotechnology. So far chemical modifications and protein engineering have been used to alter the catalytic power of the enzymes. For the first time, it is demonstrated that an exposure of enzyme to anhydrous organic solvents at optimized high temperature enhances its catalytic power through local changes at the binding region. Six enzymes: proteinase K, wheat germ acid phosphatase, alpha-amylase, beta-glucosidase, chymotrypsin and trypsin have been exposed to acetonitrile at 70 degrees C for three hours. The activities of these enzymes were found to be considerably enhanced. In order to understand the basis of this change in the activity of these enzymes, the structure of one of these treated enzymes, proteinase K has been analyzed in detail using X-ray diffraction method. The overall structure of the enzyme is similar to the native structure in aqueous environment. The hydrogen bonding system of the catalytic triad is intact after the treatment. However, the water structure in the substrate binding site undergoes some rearrangement as some of the water molecules are either displaced or completely absent. The most striking observation concerning the water structure pertains to the complete deletion of the water molecule which occupied the position at the so-called oxyanion hole in the active site of the native enzyme. Three acetonitrile molecules were found in the present structure. All the acetonitrile molecules are located in the recognition site. The sites occupied by acetonitrile molecules are independent of water molecules. The acetonitrile molecules are involved in extensive interactions with the protein atoms. All of them are interlinked through water molecules. The methyl group of one of the acetonitrile molecules (CCN1) interacts simultaneously with the hydrophobic side chains of Leu-96, Ile-107, and Leu-133. The development of such a hydrophobic environment at the recognition site introduces a striking conformation change in Ile-107 by rotating its side chain about C(alpha)--C(beta) bond by 180 degrees to bring about the delta-methyl group within the range of attractive van der Waals interactions with the methyl group of CCN1. A similar change has earlier been observed in proteinase K when it is complexed to a substrate analog lactoferrin fragment.

Thermodynamic of cellulose solvation in novel solvent mixtures

NASA Astrophysics Data System (ADS)

Das, Ritankar; Chu, Jhih-Wei

2013-04-01

Biomass contains abundant amounts of cellulose as crystalline microfibrils. A limiting step to using cellulose as an alternative energy source, however, is the hydrolysis of the biomass and subsequent transformation into fuels. Cellulose is insoluble in most solvents including organic solvents and water, but it is soluble in some ionic liquids like BMIM-Cl. This project aims to find alternative solvents that are less expensive and are more environmentally benign than the ionic liquids. All-atom molecular dynamics simulations were performed on dissociated glucan chains separated by multiple (4-5) solvation shells, in the presence of several novel solvents and solvent mixtures. The solubility of the chains in each solvent was indicated by contacts calculations after the equilibration of the molecular dynamics. It was discovered that pyridine and imidazole acted as the best solvents because their aromatic electronic structure was able to effectively disrupt the inter-sheet interactions among the glucan chains in the axial direction, and because perturbation of the solvent interactions in the presence of glucan chains was minimal.

Thermodynamic of cellulose solvation in novel solvent mixtures

NASA Astrophysics Data System (ADS)

Das, Ritankar

2013-03-01

Biomass contains abundant amounts of cellulose as crystalline microfibrils. A limiting step to using cellulose as an alternative energy source, however, is the hydrolysis of the biomass and subsequent transformation into fuels. Cellulose is insoluble in most solvents including organic solvents and water, but it is soluble in some ionic liquids like BMIM-Cl. This project aims to find alternative solvents that are less expensive and are more environmentally benign than the ionic liquids. All-atom molecular dynamics simulations were performed on dissociated glucan chains separated by multiple (4-5) solvation shells, in the presence of several novel solvents and solvent mixtures. The solubility of the chains in each solvent was indicated by contacts calculations after the equilibration of the molecular dynamics. It was discovered that pyridine and imidazole acted as the best solvents because their aromatic electronic structure was able to effectively disrupt the inter-sheet interactions among the glucan chains in the axial direction, and because perturbation of the solvent interactions in the presence of glucan chains was minimal.

Thermodynamics of cellulose solvation in novel solvent mixtures

NASA Astrophysics Data System (ADS)

Das, Ritankar; Chu, Jhih-Wei

2012-10-01

Biomass contains abundant amounts of cellulose as crystalline microfibrils. A limiting step to using cellulose as an alternative energy source, however, is the hydrolysis of the biomass and subsequent transformation into fuels. Cellulose is insoluble in most solvents including organic solvents and water, but it is soluble in some ionic liquids like BMIM-Cl. This project aims to find alternative solvents that are less expensive and are more environmentally benign than the ionic liquids. All-atom molecular dynamics simulations were performed on dissociated glucan chains separated by multiple (4-5) solvation shells, in the presence of several novel solvents and solvent mixtures. The solubility of the chains in each solvent was indicated by contacts calculations after the equilibration of the molecular dynamics. It was discovered that pyridine and imidazole acted as the best solvents because their aromatic electronic structure was able to effectively disrupt the inter-sheet interactions among the glucan chains in the axial direction, and because perturbation of the solvent interactions in the presence of glucan chains was minimal.

Thermodynamic of cellulose solvation in novel solvent mixtures

NASA Astrophysics Data System (ADS)

Das, Ritankar

2012-11-01

Biomass contains abundant amounts of cellulose as crystalline microfibrils. A limiting step to using cellulose as an alternative energy source, however, is the hydrolysis of the biomass and subsequent transformation into fuels. Cellulose is insoluble in most solvents including organic solvents and water, but it is soluble in some ionic liquids like BMIM-Cl. This project aims to find alternative solvents that are less expensive and are more environmentally benign than the ionic liquids. All-atom molecular dynamics simulations were performed on dissociated glucan chains separated by multiple (4-5) solvation shells, in the presence of several novel solvents and solvent mixtures. The solubility of the chains in each solvent was indicated by contacts calculations after the equilibration of the molecular dynamics. It was discovered that pyridine and imidazole acted as the best solvents because their aromatic electronic structure was able to effectively disrupt the inter-sheet interactions among the glucan chains in the axial direction, and because perturbation of the solvent interactions in the presence of glucan chains was minimal.

Impaired colour vision in workers exposed to organic solvents: A systematic review.

PubMed

Betancur-Sánchez, A M; Vásquez-Trespalacios, E M; Sardi-Correa, C

2017-01-01

To evaluate recent evidence concerning the relationship between the exposure to organic solvents and the impairment of colour vision. A bibliographic search was conducted for scientific papers published in the last 15 years, in the LILACS, PubMed, Science Direct, EBSCO, and Cochrane databases that included observational studies assessing the relationship between impairment in colour vision and exposure to organic solvents. Eleven studies were selected that were performed on an economically active population and used the Lanthony D-15 desaturated test (D-15d), measured the exposure to organic solvents, and included unexposed controls. It was found that there is a statistically significant relationship between the exposure to organic solvents and the presence of an impairment in colour vision. The results support the hypothesis that exposure to organic solvents could induce acquired dyschromatopsia. The evaluation of colour vision with the D-15d test is simple and sensitive for diagnosis. More studies need to be conducted on this subject in order to better understand the relationship between impaired colour vision and more severe side effects caused by this exposure. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

The Nature of the Intramolecular Charge Transfer State in Peridinin

PubMed Central

Wagner, Nicole L.; Greco, Jordan A.; Enriquez, Miriam M.; Frank, Harry A.; Birge, Robert R.

2013-01-01

Experimental and theoretical evidence is presented that supports the theory that the intramolecular charge transfer (ICT) state of peridinin is an evolved state formed via excited-state bond-order reversal and solvent reorganization in polar media. The ICT state evolves in <100 fs and is characterized by a large dipole moment (∼35 D). The charge transfer character involves a shift of electron density within the polyene chain, and it does not involve participation of molecular orbitals localized in either of the β-rings. Charge is moved from the allenic side of the polyene into the furanic ring region and is accompanied by bond-order reversal in the central portion of the polyene chain. The electronic properties of the ICT state are generated via mixing of the “11Bu+” ionic state and the lowest-lying “21Ag–” covalent state. The resulting ICT state is primarily 1Bu+-like in character and exhibits not only a large oscillator strength but an unusually large doubly excited character. In most solvents, two populations exist in equilibrium, one with a lowest-lying ICT ionic state and a second with a lowest-lying “21Ag–” covalent state. The two populations are separated by a small barrier associated with solvent relaxation and cavity formation. PMID:23528091

PDB_Hydro: incorporating dipolar solvents with variable density in the Poisson-Boltzmann treatment of macromolecule electrostatics.

PubMed

Azuara, Cyril; Lindahl, Erik; Koehl, Patrice; Orland, Henri; Delarue, Marc

2006-07-01

We describe a new way to calculate the electrostatic properties of macromolecules which eliminates the assumption of a constant dielectric value in the solvent region, resulting in a Generalized Poisson-Boltzmann-Langevin equation (GPBLE). We have implemented a web server (http://lorentz.immstr.pasteur.fr/pdb_hydro.php) that both numerically solves this equation and uses the resulting water density profiles to place water molecules at preferred sites of hydration. Surface atoms with high or low hydration preference can be easily displayed using a simple PyMol script, allowing for the tentative prediction of the dimerization interface in homodimeric proteins, or lipid binding regions in membrane proteins. The web site includes options that permit mutations in the sequence as well as reconstruction of missing side chain and/or main chain atoms. These tools are accessible independently from the electrostatics calculation, and can be used for other modeling purposes. We expect this web server to be useful to structural biologists, as the knowledge of solvent density should prove useful to get better fits at low resolution for X-ray diffraction data and to computational biologists, for whom these profiles could improve the calculation of interaction energies in water between ligands and receptors in docking simulations.

A single-point mutation in the extreme heat- and pressure-resistant sso7d protein from sulfolobus solfataricus leads to a major rearrangement of the hydrophobic core.

PubMed

Consonni, R; Santomo, L; Fusi, P; Tortora, P; Zetta, L

1999-09-28

Sso7d is a basic 7-kDa DNA-binding protein from Sulfolobus solfataricus, also endowed with ribonuclease activity. The protein consists of a double-stranded antiparallel beta-sheet, onto which an orthogonal triple-stranded antiparallel beta-sheet is packed, and of a small helical stretch at the C-terminus. Furthermore, the two beta-sheets enclose an aromatic cluster displaying a fishbone geometry. We previously cloned the Sso7d-encoding gene, expressed it in Escherichia coli, and produced several single-point mutants, either of residues located in the hydrophobic core or of Trp23, which is exposed to the solvent and plays a major role in DNA binding. The mutation F31A was dramatically destabilizing, with a loss in thermo- and piezostabilities by at least 27 K and 10 kbar, respectively. Here, we report the solution structure of the F31A mutant, which was determined by NMR spectroscopy using 744 distance constraints obtained from analysis of multidimensional spectra in conjunction with simulated annealing protocols. The most remarkable finding is the change in orientation of the Trp23 side chain, which in the wild type is completely exposed to the solvent, whereas in the mutant is largely buried in the aromatic cluster. This prevents the formation of a cavity in the hydrophobic core of the mutant, which would arise in the absence of structural rearrangements. We found additional changes produced by the mutation, notably a strong distortion in the beta-sheets with loss in several hydrogen bonds, increased flexibility of some stretches of the backbone, and some local strains. On one hand, these features may justify the dramatic destabilization provoked by the mutation; on the other hand, they highlight the crucial role of the hydrophobic core in protein stability. To the best of our knowledge, no similar rearrangement has been so far described as a result of a single-point mutation.

Hydration structure of the α-chymotrypsin substrate binding pocket: the impact of constrained geometry

NASA Astrophysics Data System (ADS)

Carey, Christina; Cheng, Yuen-Kit; Rossky, Peter J.

2000-08-01

The concave substrate binding pocket of α-chymotrypsin binds specifically hydrophobic side chains. In order to understand the hydration structure present in the absence of substrate, and elucidate the character of the solvent displaced on binding, molecular dynamics computer simulation of the solvent in a fully hydrated protein has been carried out and analyzed. The pocket is found to be characterized in terms of a mixed polar and apolar macromolecular surface. It is shown that the simulated solvent structure within it is spatially consistent with that seen via crystallography. The solvent structure is energetically characterized by large losses in hydrogen bonding among solvent molecules except at the mouth of the pocket where exposure to bulk-like solvent is possible. The loss in hydrogen bonding is attributed to the highly constrained geometry available to the solvent, preventing formation of a hydrogen bonding network, with only partial compensation by interactions with the macromolecular surface. The solvent displacement concomitant with substrate binding will therefore be associated with a large enthalpic driving force. This result is at the extreme of a continuum of variable cases of "hydrophobic" hydration, which differ most basically in surface curvature. These range from convex solute surfaces, inducing clathrate-like structures, with negligible hydrogen bond loss, to flat surfaces with significant interfacial loss, to the present concave case with hydrogen bonding losses exceeding 50%.

Assessment of central auditory processing in a group of workers exposed to solvents.

PubMed

Fuente, Adrian; McPherson, Bradley; Muñoz, Verónica; Pablo Espina, Juan

2006-12-01

Despite having normal hearing thresholds and speech recognition thresholds, results for central auditory tests were abnormal in a group of workers exposed to solvents. Workers exposed to solvents may have difficulties in everyday listening situations that are not related to a decrement in hearing thresholds. A central auditory processing disorder may underlie these difficulties. To study central auditory processing abilities in a group of workers occupationally exposed to a mix of organic solvents. Ten workers exposed to a mix of organic solvents and 10 matched non-exposed workers were studied. The test battery comprised pure-tone audiometry, tympanometry, acoustic reflex measurement, acoustic reflex decay, dichotic digit, pitch pattern sequence, masking level difference, filtered speech, random gap detection and hearing-in-noise tests. All the workers presented normal hearing thresholds and no signs of middle ear abnormalities. Workers exposed to solvents had lower results in comparison with the control group and previously reported normative data, in the majority of the tests.

Macromolecular properties of cepacian in water and in dimethylsulfoxide.

PubMed

Herasimenka, Yury; Cescutti, Paola; Sampaio Noguera, Carlos E; Ruggiero, Josè R; Urbani, Ranieri; Impallomeni, Giuseppe; Zanetti, Flavio; Campidelli, Stéphane; Prato, Maurizio; Rizzo, Roberto

2008-01-14

Cepacian is the exopolysaccharide produced by the majority of the so far investigated clinical strains of the Burkholderia cepacia complex. This is a group of nine closely related bacterial species that might cause serious lung infections in cystic fibrosis patients, in some cases leading to death. In this paper the aggregation ability and the conformational properties of cepacian chain were investigated to understand its role in biofilm formation. Viscosity and atomic force microscopy studies in water and in mixed (dimethylsulfoxide/water) solvent indicated the formation of double stranded molecular structures in aqueous solutions. Inter-residue short distances along cepacian chain were investigated by NOE NMR, which showed that two side chains of cepacian were not conformationally free due to strong interactions with the polymer backbone. These interactions were attributed to hydrogen bonding and contributed to structure rigidity.

Optocontrol of glutamate receptor activity by single side-chain photoisomerization

PubMed Central

Klippenstein, Viktoria; Hoppmann, Christian; Ye, Shixin; Wang, Lei; Paoletti, Pierre

2017-01-01

Engineering light-sensitivity into proteins has wide ranging applications in molecular studies and neuroscience. Commonly used tethered photoswitchable ligands, however, require solvent-accessible protein labeling, face structural constrains, and are bulky. Here, we designed a set of optocontrollable NMDA receptors by directly incorporating single photoswitchable amino acids (PSAAs) providing genetic encodability, reversibility, and site tolerance. We identified several positions within the multi-domain receptor endowing robust photomodulation. PSAA photoisomerization at the GluN1 clamshell hinge is sufficient to control glycine sensitivity and activation efficacy. Strikingly, in the pore domain, flipping of a M3 residue within a conserved transmembrane cavity impacts both gating and permeation properties. Our study demonstrates the first detection of molecular rearrangements in real-time due to the reversible light-switching of single amino acid side-chains, adding a dynamic dimension to protein site-directed mutagenesis. This novel approach to interrogate neuronal protein function has general applicability in the fast expanding field of optopharmacology. DOI: http://dx.doi.org/10.7554/eLife.25808.001 PMID:28534738

Probing energetics of Abeta fibril elongation by molecular dynamics simulations.

PubMed

Takeda, Takako; Klimov, Dmitri K

2009-06-03

Using replica exchange molecular dynamics simulations and an all-atom implicit solvent model, we probed the energetics of Abeta(10-40) fibril growth. The analysis of the interactions between incoming Abeta peptides and the fibril led us to two conclusions. First, considerable variations in fibril binding propensities are observed along the Abeta sequence. The peptides in the fibril and those binding to its edge interact primarily through their N-termini. Therefore, the mutations affecting the Abeta positions 10-23 are expected to have the largest impact on fibril elongation compared with those occurring in the C-terminus and turn. Second, we performed weak perturbations of the binding free energy landscape by scanning partial deletions of side-chain interactions at various Abeta sequence positions. The results imply that strong side-chain interactions--in particular, hydrophobic contacts--impede fibril growth by favoring disordered docking of incoming peptides. Therefore, fibril elongation may be promoted by moderate reduction of Abeta hydrophobicity. The comparison with available experimental data is presented.

Protein Conformational Entropy is Independent of Solvent

NASA Astrophysics Data System (ADS)

Nucci, Nathaniel; Moorman, Veronica; Gledhill, John; Valentine, Kathleen; Wand, A. Joshua

Proteins exhibit most of their conformational entropy in individual bond vector motions on the ps-ns timescale. These motions can be examined through determination of the Lipari-Szabo generalized squared order parameter (O2) using NMR spin relaxation measurements. It is often argued that most protein motions are intimately dependent on the nature of the solvating environment. Here the solvent dependence of the fast protein dynamics is directly assessed. Using the model protein ubiquitin, the order parameters of the backbone and methyl groups are shown to be generally unaffected by up to a six-fold increase in bulk viscosity or by encapsulation in the nanoscale interior of a reverse micelle. In addition, the reverse micelle condition permits direct comparison of protein dynamics to the mobility of the hydration layer; no correlation is observed. The dynamics of aromatic side chains are also assessed and provide an estimate of the length- and timescale of protein motions where solvent dependence is seen. These data demonstrate the solvent independence of conformational entropy, clarifying a long-held misconception in the fundamental behavior of biological macromolecules. Supported by the National Science Foundation.

Using ethane and butane as probes to the molecular structure of 1-alkyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl] imide ionic liquids.

PubMed

Costa Gomes, Margarida F; Pison, Laure; Pensado, Alfonso S; Pádua, Agilio A H

2012-01-01

In this work, we have studied the solubility and the thermodynamic properties of solvation, between 298 and 343 K and at pressures close to atmospheric, of ethane and n-butane in several ionic liquids based on the bis[(trifluoromethyl) sulfonyl]imide anion and on 1-alkyl-3-methylimidazolium cations, [CnC1Im] [NTf2], with alkyl side-chains varying from two to ten carbon atoms. The solubility of butane is circa one order of magnitude larger than that of ethane with mole fractions as high as 0.15 in [C10C1Im][NTf2] at 300 K. The solubilities of both n-butane and ethane gases are higher for ionic liquids with longer alkyl chains. The behaviour encountered is explained by the preferential solvation of the gases in the non-polar domains of the solvents, the larger solubility of n-butane being attributed to the dispersive contributions to the interaction energy. The rise in solubility with increasing size of the alkyl-side chain is explained by a more favourable entropy of solvation in the ionic liquids with larger cations. These conclusions are corroborated by molecular dynamics simulation studies.

Specific material recognition by small peptides mediated by the interfacial solvent structure.

PubMed

Schneider, Julian; Ciacchi, Lucio Colombi

2012-02-01

We present evidence that specific material recognition by small peptides is governed by local solvent density variations at solid/liquid interfaces, sensed by the side-chain residues with atomic-scale precision. In particular, we unveil the origin of the selectivity of the binding motif RKLPDA for Ti over Si using a combination of metadynamics and steered molecular dynamics simulations, obtaining adsorption free energies and adhesion forces in quantitative agreement with corresponding experiments. For an accurate description, we employ realistic models of the natively oxidized surfaces which go beyond the commonly used perfect crystal surfaces. These results have profound implications for nanotechnology and materials science applications, offering a previously missing structure-function relationship for the rational design of materials-selective peptide sequences. © 2011 American Chemical Society

Solvent and substituent effects on aggregation constants of perylene bisimide π-stacks--a linear free energy relationship analysis.

PubMed

Chen, Zhijian; Fimmel, Benjamin; Würthner, Frank

2012-08-14

A series of six perylene bisimides (PBIs) with hydrophilic and hydrophobic side chains at the imide nitrogens were applied for a comparative study of the solvent and structural effects on the aggregation behaviour of this class of dyes. A comparison of the binding constants in tetrachloromethane at room temperature revealed the highest binding constant of about 10(5) M(-1) for a PBI bearing 3,4,5-tridodecyloxyphenyl substituents at the imide nitrogens, followed by 3,4,5-tridodecylphenyl and alkyl-substituted PBIs, whereas no aggregation could be observed in the accessible concentration range for PBIs equipped with bulky 2,6-diisopropylphenyl substituents at the imide nitrogens. The aggregation behaviour of three properly soluble compounds was investigated in 17 different solvents covering a broad polarity range from nonpolar n-hexane to highly polar DMSO and water. Linear free energy relationships (LFER) revealed a biphasic behaviour between Gibbs free energies of aggregation and common empirical solvent polarity scales indicating particularly strong π-π stacking interactions in nonpolar aliphatic and polar alcoholic solvents whilst the weakest binding is observed in dichloromethane and chloroform. Accordingly, PBI aggregation is dominated by electrostatic interactions in nonpolar solvents and by solvophobic interactions in protic solvents. In water, the aggregation constant is increased far beyond LFER expectations pointing at a pronounced hydrophobic effect.

Reconstructing Solvent Density of Myoglobin Unit Cell from Proximal Radial Distribution Functions of Amino Acids

NASA Astrophysics Data System (ADS)

Galbraith, Madeline; Lynch, Gc; Pettitt, Bm

Understanding the solvent density around a protein crystal structure is an important step for refining accurate crystal structures for use in dynamics simulations or in free energy calculations. The free energy of solvation has typically been approximated using an implicit continuum solvent model or an all atom MD simulation, with a trade-off between accuracy and computation time. For proteins, using precomputed proximal radial distribution functions (pRDFs) of the solvent to reconstruct solvent density on a grid is much faster than all atom MD simulations and more accurate than using implicit solvent models. MD simulations were run for the 20 common amino acids and pRDFs were calculated for several atom type data sets with and without hydrogens, using atom types representative of amino acid side chain atoms. Preliminary results from reconstructions suggest using a data set with 15 heavy atoms and 3 hydrogen yields results with the lowest error without a tradeoff on time. The results of using precomputed pRDFs to reconstruct the solvent density of water for the myoglobin (pdb ID 2mgk) unit cell quantifies the accuracy of the method in comparison with the crystallographic data. Funding Acknowledgement: This research was funded by the CPRIT Summer Undergraduate Program in Computational Cancer Biology, training Grant award RP 140113 from the Cancer Prevention & Research Institute of Texas (CPRIT).

Gold nanorod linking to control plasmonic properties in solution and polymer nanocomposites.

PubMed

Ferrier, Robert C; Lee, Hyun-Su; Hore, Michael J A; Caporizzo, Matthew; Eckmann, David M; Composto, Russell J

2014-02-25

A novel, solution-based method is presented to prepare bifunctional gold nanorods (B-NRs), assemble B-NRs end-to-end in various solvents, and disperse linked B-NRs in a polymer matrix. The B-NRs have poly(ethylene glycol) grafted along its long axis and cysteine adsorbed to its ends. By controlling cysteine coverage, bifunctional ligands or polymer can be end-grafted to the AuNRs. Here, two dithiol ligands (C6DT and C9DT) are used to link the B-NRs in organic solvents. With increasing incubation time, the nanorod chain length increases linearly as the longitudinal surface plasmon resonance shifts toward lower adsorption wavelengths (i.e., red shift). Analogous to step-growth polymerization, the polydispersity in chain length also increases. Upon adding poly(ethylene glycol) or poly(methyl methacrylate) to chloroform solution with linked B-NR, the nanorod chains are shown to retain end-to-end linking upon spin-casting into PEO or PMMA films. Using quartz crystal microbalance with dissipation (QCM-D), the mechanism of nanorod linking is investigated on planar gold surfaces. At submonolayer coverage of cysteine, C6DT molecules can insert between cysteines and reach an areal density of 3.4 molecules per nm(2). To mimic the linking of Au NRs, this planar surface is exposed to cysteine-coated Au nanoparticles, which graft at 7 NPs per μm(2). This solution-based method to prepare, assemble, and disperse Au nanorods is applicable to other nanorod systems (e.g., CdSe) and presents a new strategy to assemble anisotropic particles in organic solvents and polymer coatings.

Gold Nanorod Linking to Control Plasmonic Properties in Solution and Polymer Nanocomposites

PubMed Central

2015-01-01

A novel, solution-based method is presented to prepare bifunctional gold nanorods (B-NRs), assemble B-NRs end-to-end in various solvents, and disperse linked B-NRs in a polymer matrix. The B-NRs have poly(ethylene glycol) grafted along its long axis and cysteine adsorbed to its ends. By controlling cysteine coverage, bifunctional ligands or polymer can be end-grafted to the AuNRs. Here, two dithiol ligands (C6DT and C9DT) are used to link the B-NRs in organic solvents. With increasing incubation time, the nanorod chain length increases linearly as the longitudinal surface plasmon resonance shifts toward lower adsorption wavelengths (i.e., red shift). Analogous to step-growth polymerization, the polydispersity in chain length also increases. Upon adding poly(ethylene glycol) or poly(methyl methacrylate) to chloroform solution with linked B-NR, the nanorod chains are shown to retain end-to-end linking upon spin-casting into PEO or PMMA films. Using quartz crystal microbalance with dissipation (QCM-D), the mechanism of nanorod linking is investigated on planar gold surfaces. At submonolayer coverage of cysteine, C6DT molecules can insert between cysteines and reach an areal density of 3.4 molecules per nm2. To mimic the linking of Au NRs, this planar surface is exposed to cysteine-coated Au nanoparticles, which graft at 7 NPs per μm2. This solution-based method to prepare, assemble, and disperse Au nanorods is applicable to other nanorod systems (e.g., CdSe) and presents a new strategy to assemble anisotropic particles in organic solvents and polymer coatings. PMID:24483622

Direct determination of protonation states and visualization of hydrogen bonding in a glycoside hydrolase with neutron crystallography.

PubMed

Wan, Qun; Parks, Jerry M; Hanson, B Leif; Fisher, Suzanne Zoe; Ostermann, Andreas; Schrader, Tobias E; Graham, David E; Coates, Leighton; Langan, Paul; Kovalevsky, Andrey

2015-10-06

Glycoside hydrolase (GH) enzymes apply acid/base chemistry to catalyze the decomposition of complex carbohydrates. These ubiquitous enzymes accept protons from solvent and donate them to substrates at close to neutral pH by modulating the pKa values of key side chains during catalysis. However, it is not known how the catalytic acid residue acquires a proton and transfers it efficiently to the substrate. To better understand GH chemistry, we used macromolecular neutron crystallography to directly determine protonation and ionization states of the active site residues of a family 11 GH at multiple pD (pD=pH+0.4) values. The general acid glutamate (Glu) cycles between two conformations, upward and downward, but is protonated only in the downward orientation. We performed continuum electrostatics calculations to estimate the pKa values of the catalytic Glu residues in both the apo- and substrate-bound states of the enzyme. The calculated pKa of the Glu increases substantially when the side chain moves down. The energy barrier required to rotate the catalytic Glu residue back to the upward conformation, where it can protonate the glycosidic oxygen of the substrate, is 4.3 kcal/mol according to free energy simulations. These findings shed light on the initial stage of the glycoside hydrolysis reaction in which molecular motion enables the general acid catalyst to obtain a proton from the bulk solvent and deliver it to the glycosidic oxygen.

Direct determination of protonation states and visualization of hydrogen bonding in a glycoside hydrolase with neutron crystallography

PubMed Central

Wan, Qun; Parks, Jerry M.; Hanson, B. Leif; Fisher, Suzanne Zoe; Ostermann, Andreas; Schrader, Tobias E.; Graham, David E.; Coates, Leighton; Langan, Paul; Kovalevsky, Andrey

2015-01-01

Glycoside hydrolase (GH) enzymes apply acid/base chemistry to catalyze the decomposition of complex carbohydrates. These ubiquitous enzymes accept protons from solvent and donate them to substrates at close to neutral pH by modulating the pKa values of key side chains during catalysis. However, it is not known how the catalytic acid residue acquires a proton and transfers it efficiently to the substrate. To better understand GH chemistry, we used macromolecular neutron crystallography to directly determine protonation and ionization states of the active site residues of a family 11 GH at multiple pD (pD = pH + 0.4) values. The general acid glutamate (Glu) cycles between two conformations, upward and downward, but is protonated only in the downward orientation. We performed continuum electrostatics calculations to estimate the pKa values of the catalytic Glu residues in both the apo- and substrate-bound states of the enzyme. The calculated pKa of the Glu increases substantially when the side chain moves down. The energy barrier required to rotate the catalytic Glu residue back to the upward conformation, where it can protonate the glycosidic oxygen of the substrate, is 4.3 kcal/mol according to free energy simulations. These findings shed light on the initial stage of the glycoside hydrolysis reaction in which molecular motion enables the general acid catalyst to obtain a proton from the bulk solvent and deliver it to the glycosidic oxygen. PMID:26392527

Direct determination of protonation states and visualization of hydrogen bonding in a glycoside hydrolase with neutron crystallography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan, Qun; Parks, Jerry M.; Hanson, B. Leif

Glycoside hydrolase (GH) enzymes apply acid/base chemistry to catalyze the decomposition of complex carbohydrates. These ubiquitous enzymes accept protons from solvent and donate them to substrates at close to neutral pH by modulating the pK a values of key side chains during catalysis. However, it is not known how the catalytic acid residue acquires a proton and transfers it efficiently to the substrate. To better understand GH chemistry, we used macromolecular neutron crystallography to directly determine protonation and ionization states of the active site residues of a family 11 GH at multiple pD (pD = pH + 0.4) values. Themore » general acid glutamate (Glu) cycles between two conformations, upward and downward, but is protonated only in the downward orientation. We performed continuum electrostatics calculations to estimate the pK a values of the catalytic Glu residues in both the apo- and substrate-bound states of the enzyme. The calculated pK a of the Glu increases substantially when the side chain moves down. The energy barrier required to rotate the catalytic Glu residue back to the upward conformation, where it can protonate the glycosidic oxygen of the substrate, is 4.3 kcal/mol according to free energy simulations. Lastly, these findings shed light on the initial stage of the glycoside hydrolysis reaction in which molecular motion enables the general acid catalyst to obtain a proton from the bulk solvent and deliver it to the glycosidic oxygen.« less

Direct determination of protonation states and visualization of hydrogen bonding in a glycoside hydrolase with neutron crystallography

DOE PAGES

Wan, Qun; Parks, Jerry M.; Hanson, B. Leif; ...

2015-09-21

Glycoside hydrolase (GH) enzymes apply acid/base chemistry to catalyze the decomposition of complex carbohydrates. These ubiquitous enzymes accept protons from solvent and donate them to substrates at close to neutral pH by modulating the pK a values of key side chains during catalysis. However, it is not known how the catalytic acid residue acquires a proton and transfers it efficiently to the substrate. To better understand GH chemistry, we used macromolecular neutron crystallography to directly determine protonation and ionization states of the active site residues of a family 11 GH at multiple pD (pD = pH + 0.4) values. Themore » general acid glutamate (Glu) cycles between two conformations, upward and downward, but is protonated only in the downward orientation. We performed continuum electrostatics calculations to estimate the pK a values of the catalytic Glu residues in both the apo- and substrate-bound states of the enzyme. The calculated pK a of the Glu increases substantially when the side chain moves down. The energy barrier required to rotate the catalytic Glu residue back to the upward conformation, where it can protonate the glycosidic oxygen of the substrate, is 4.3 kcal/mol according to free energy simulations. Lastly, these findings shed light on the initial stage of the glycoside hydrolysis reaction in which molecular motion enables the general acid catalyst to obtain a proton from the bulk solvent and deliver it to the glycosidic oxygen.« less

Functionalizing CNTs for Making Epoxy/CNT Composites

NASA Technical Reports Server (NTRS)

Chen, Jian; Rajagopal, Ramasubramaniam

2009-01-01

Functionalization of carbon nanotubes (CNTs) with linear molecular side chains of polyphenylene ether (PPE) has been shown to be effective in solubilizing the CNTs in the solvent components of solutions that are cast to make epoxy/CNT composite films. (In the absence of solubilization, the CNTs tend to clump together instead of becoming dispersed in solution as needed to impart, to the films, the desired CNT properties of electrical conductivity and mechanical strength.) Because the PPE functionalizes the CNTs in a noncovalent manner, the functionalization does not damage the CNTs. The functionalization can also be exploited to improve the interactions between CNTs and epoxy matrices to enhance the properties of the resulting composite films. In addition to the CNTs, solvent, epoxy resin, epoxy hardener, and PPE, a properly formulated solution also includes a small amount of polycarbonate, which serves to fill voids that, if allowed to remain, would degrade the performance of the film. To form the film, the solution is drop-cast or spin-cast, then the solvent is allowed to evaporate.

Branched polyesters based on poly[vinyl-3-(dialkylamino)alkylcarbamate-co-vinyl acetate-co-vinyl alcohol]-graft-poly(D,L-lactide-co-glycolide): effects of polymer structure on in vitro degradation behaviour.

PubMed

Unger, Florian; Wittmar, Matthias; Morell, Frank; Kissel, Thomas

2008-05-01

Branched polyesters of the general structure poly[vinyl-3-(dialkylamino)alkylcarbamate-co-vinyl acetate-co-vinyl alcohol]-graft-poly(D,L-lactide-co-glycolide) have shown potential for nano- and micro-scale drug delivery systems. Here the in vitro degradation behaviour with a special emphasis on elucidating structure-property relationships is reported. Effects of type and degree of amine substitution as well as PLGA side chain length were considered. In a first set of experiment, the weight loss of solvent cast films of defined size from 19 polymers was measured as a function of incubation in phosphate buffer (pH 7.4) at 37 degrees C over a time of 21 days. A second study was initiated focusing on three selected polymers in a similar set up, but with additional observation of pH influences (pH 2 and pH 9) and determination of water uptake (swelling) and molecular weights during degradation. Scanning electron micrographs have been recorded at selected time points to characterize film specimens morphologically after degradation. Our investigations revealed the potential to influence the degradation of this polymer class by the degree of amine substitution, higher degrees leading to faster erosion. The erosion rate could further be influenced by the type of amine functionality, DEAPA-modified polyesters degrading as fast as or slightly faster than DMAPA-modified polyesters and these degrading faster than DEAEA-PVA-g-PLGA. As a third option the degradation rate could be modified by the PLGA side chain length, shorter side chains leading to faster erosion. As compared to linear PLGA, remarkably shorter degradation times could be achieved by grafting short PLGA side chains onto amine-modified PVA backbones. Erosion times from less than 5 days to more than 4 weeks could be realized by selecting the type of amine functionality, the degree of amine substitution and the PLGA side chain length at the time of synthesis. In addition, the pathway of hydrolytic degradation can be tuned to be either mainly bulk or surface erosion.

First-second shell interactions in metal binding sites in proteins: a PDB survey and DFT/CDM calculations.

PubMed

Dudev, Todor; Lin, Yen-lin; Dudev, Minko; Lim, Carmay

2003-03-12

The role of the second shell in the process of metal binding and selectivity in metalloproteins has been elucidated by combining Protein Data Bank (PDB) surveys of Mg, Mn, Ca, and Zn binding sites with density functional theory/continuum dielectric methods (DFT/CDM). Peptide backbone groups were found to be the most common second-shell ligand in Mg, Mn, Ca, and Zn binding sites, followed (in decreasing order) by Asp/Glu, Lys/Arg, Asn/Gln, and Ser/Thr side chains. Aromatic oxygen- or nitrogen-containing side chains (Tyr, His, and Trp) and sulfur-containing side chains (Cys and Met) are seldom found in the second coordination layer. The backbone and Asn/Gln side chain are ubiquitous in the metal second coordination layer as their carbonyl oxygen and amide hydrogen can act as a hydrogen-bond acceptor and donor, respectively, and can therefore partner practically every first-shell ligand. The second most common outer-shell ligand, Asp/Glu, predominantly hydrogen bonds to a metal-bound water or Zn-bound histidine and polarizes the H-O or H-N bond. In certain cases, a second-shell Asp/Glu could affect the protonation state of the metal ligand. It could also energetically stabilize a positively charged metal complex more than a neutral ligand such as the backbone and Asn/Gln side chain. As for the first shell, the second shell is predicted to contribute to the metal selectivity of the binding site by discriminating between metal cations of different ionic radii and coordination geometries. The first-shell-second-shell interaction energies decay rapidly with increasing solvent exposure of the metal binding site. They are less favorable but are of the same order of magnitude as compared to the respective metal-first-shell interaction energies. Altogether, the results indicate that the structure and properties of the second shell are dictated by those of the first layer. The outer shell is apparently designed to stabilize/protect the inner-shell and complement/enhance its properties.

An ellipsoid-chain model for conjugated polymer solutions

NASA Astrophysics Data System (ADS)

Lee, Cheng K.; Hua, Chi C.; Chen, Show A.

2012-02-01

We propose an ellipsoid-chain model which may be routinely parameterized to capture large-scale properties of semiflexible, amphiphilic conjugated polymers in various solvent media. The model naturally utilizes the defect locations as pivotal centers connecting adjacent ellipsoids (each currently representing ten monomer units), and a variant umbrella-sampling scheme is employed to construct the potentials of mean force (PMF) for specific solvent media using atomistic dynamics data and simplex optimization. The performances, both efficacy and efficiency, of the model are thoroughly evaluated by comparing the simulation results on long, single-chain (i.e., 300-mer) structures with those from two existing, finer-grained models for a standard conjugated polymer (i.e., poly(2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene) or MEH-PPV) in two distinct solvents (i.e., chloroform or toluene) as well as a hybrid, binary-solvent medium (i.e., chloroform/toluene = 1:1 in number density). The coarse-grained Monte Carlo (CGMC) simulation of the ellipsoid-chain model is shown to be the most efficient—about 300 times faster than the coarse-grained molecular dynamics (CGMD) simulation of the finest CG model that employs explicit solvents—in capturing elementary single-chain structures for both single-solvent media, and is a few times faster than the coarse-grained Langevin dynamics (CGLD) simulation of another implicit-solvent polymer model with a slightly greater coarse-graining level than in the CGMD simulation. For the binary-solvent system considered, however, both of the two implicit-solvent schemes (i.e., CGMC and CGLD) fail to capture the effects of conspicuous concentration fluctuations near the polymer-solvent interface, arising from a pronounced coupling between the solvent molecules and different parts of the polymer. Essential physical implications are elaborated on the success as well as the failure of the two implicit-solvent CG schemes under varying solvent conditions. Within the ellipsoid-chain model, the impact of synthesized defects on local segmental ordering as well as bulk chain conformation is also scrutinized, and essential consequences in practical applications discussed. In future perspectives, we remark on strategy that takes advantage of the coordination among various CG models and simulation schemes to warrant computational efficiency and accuracy, with the anticipated capability of simulating larger-scale, many-chain aggregate systems.

Occupational solvent exposure and brain function: an fMRI study.

PubMed

Tang, Cheuk Ying; Carpenter, David M; Eaves, Emily L; Ng, Johnny; Ganeshalingam, Nimalya; Weisel, Clifford; Qian, Hua; Lange, Gudrun; Fiedler, Nancy L

2011-07-01

Deficits in cognitive function have been demonstrated among workers chronically exposed to solvents, but the neural basis for these deficits has not been shown. We used functional magnetic resonance imaging (fMRI) to compare pathophysiological changes in brain function between solvent-exposed and control workers. Painters, drywall tapers, and carpenters were recruited from the International Union of Painters and Allied Trades, District Council 9 in New York City and District Council 21 in Philadelphia, Pennsylvania, and from the Carpenters Union in New Jersey. Twenty-seven solvent-exposed and 27 control subjects of similar age, education, and occupational status completed the N-Back working memory test during fMRI. After controlling for confounders (age; lifetime marijuana, cocaine, and alcohol use; blood lead; symptoms of depression; verbal intelligence), voxelwise group analysis and regional activation levels were compared and then correlated with an index of lifetime solvent exposure. Solvent-exposed workers' performance on the N-Back was significantly worse than that of controls. Activation of the anterior cingulate, prefrontal, and parietal cortices--areas serving working memory function and attention--was also significantly lower for solvent-exposed workers relative to controls. After controlling for confounders, we observed a negative correlation between lifetime solvent exposure and activation in these same regions among the solvent-exposed workers. This study is one of the few to document neural structures affected by exposure to solvents. Our findings provide a biological mechanism for the neurobehavioral deficits in working memory and attention that have previously been reported by other groups studying the effects of chronic exposure to solvents. These imaging markers, which are consistent with the neurobehavioral measures in our subject population, are consistent with altered brain pathology caused by prolonged exposure to solvent mixtures during construction work.

Occupational Solvent Exposure and Brain Function: An fMRI Study

PubMed Central

Carpenter, David M.; Eaves, Emily L.; Ng, Johnny; Ganeshalingam, Nimalya; Weisel, Clifford; Qian, Hua; Lange, Gudrun; Fiedler, Nancy L.

2011-01-01

Background: Deficits in cognitive function have been demonstrated among workers chronically exposed to solvents, but the neural basis for these deficits has not been shown. Objectives: We used functional magnetic resonance imaging (fMRI) to compare pathophysiological changes in brain function between solvent-exposed and control workers. Methods: Painters, drywall tapers, and carpenters were recruited from the International Union of Painters and Allied Trades, District Council 9 in New York City and District Council 21 in Philadelphia, Pennsylvania, and from the Carpenters Union in New Jersey. Twenty-seven solvent-exposed and 27 control subjects of similar age, education, and occupational status completed the N-Back working memory test during fMRI. After controlling for confounders (age; lifetime marijuana, cocaine, and alcohol use; blood lead; symptoms of depression; verbal intelligence), voxelwise group analysis and regional activation levels were compared and then correlated with an index of lifetime solvent exposure. Results: Solvent-exposed workers’ performance on the N-Back was significantly worse than that of controls. Activation of the anterior cingulate, prefrontal, and parietal cortices—areas serving working memory function and attention—was also significantly lower for solvent-exposed workers relative to controls. After controlling for confounders, we observed a negative correlation between lifetime solvent exposure and activation in these same regions among the solvent-exposed workers. Conclusions: This study is one of the few to document neural structures affected by exposure to solvents. Our findings provide a biological mechanism for the neurobehavioral deficits in working memory and attention that have previously been reported by other groups studying the effects of chronic exposure to solvents. These imaging markers, which are consistent with the neurobehavioral measures in our subject population, are consistent with altered brain pathology caused by prolonged exposure to solvent mixtures during construction work. PMID:21296712

Equilibrium disorders in workers exposed to mixed solvents.

PubMed

Giorgianni, Concetto; Tanzariello, Mariagiuseppina; De Pasquale, Domenico; Brecciaroli, Renato; Spatari, Giovanna

2018-02-06

Organic solvents cause diseases of the vestibular system. However, little is known regarding the correlation between vestibular damage and exposure to organic solvents below threshold limit values. The best measure by which to evaluate vestibular disorders is static and dynamic posturography. The aim of this study was to evaluate equilibrium disorders via static and dynamic posturography in workers without clear symptoms and exposed to low doses of mixed solvents. 200 subjects were selected. Using an Otometrics device (Madsen, Denmark), all subjects endured static and dynamic posturography testing with both eyes-open and eyes-closed conditions. Results were compared with a control group of unexposed individuals. Based on the obtained data, the following results can be drawn: (a) subjects exposed to mixtures of solvents show highly significant differences regarding all static and dynamic posturography parameters in comparison to the control group; (b) posturography testing has proven to be a valid means by which to detect subliminal equilibrium disorders in subjects exposed to solvents. We can confirm that refinery workers exposed to mixtures of solvents can present subliminal equilibrium disorders. Early diagnosis of the latter is made possible by static and dynamic posturography.

Apparatus and method for removing solvent from carbon dioxide in resin recycling system

DOEpatents

Bohnert, George W [Harrisonville, MO; Hand, Thomas E [Lee's Summit, MO; DeLaurentiis, Gary M [Jamestown, CA

2009-01-06

A two-step resin recycling system and method solvent that produces essentially contaminant-free synthetic resin material. The system and method includes one or more solvent wash vessels to expose resin particles to a solvent, the solvent contacting the resin particles in the one or more solvent wash vessels to substantially remove contaminants on the resin particles. A separator is provided to separate the solvent from the resin particles after removal from the one or more solvent wash vessels. The resin particles are next exposed to carbon dioxide in a closed loop carbon dioxide system. The closed loop system includes a carbon dioxide vessel where the carbon dioxide is exposed to the resin, substantially removing any residual solvent remaining on the resin particles after separation. A separation vessel is also provided to separate the solvent from the solvent laden carbon dioxide. Both the carbon dioxide and the solvent are reused after separation in the separation vessel.

An ab initio time-dependent Hartree Fock study of solvent effects on the polarizability and second hyperpolarizability of polyacetylene chains within the polarizable continuum model

NASA Astrophysics Data System (ADS)

Champagne, Benoı̂t; Mennucci, Benedetta; Cossi, Maurizio; Cammi, Roberto; Tomasi, Jacopo

1998-11-01

The solvent effects upon the longitudinal polarizability ( αL) and second hyperpolarizability ( γL) of small all-trans polyacetylene (PA) chains ranging from C 2H 4 to C 10H 12 have been evaluated at the time-dependent Hartree-Fock (TDHF) level within the framework of the polarizable continuum model. The solvent effects, which correspond to the solvent-induced modifications of the solute properties, result in large increases of the linear and nonlinear responses even for solvents with low dielectric constants. When the dielectric constant is increased, the αL values tend to saturate at values 30%-40% larger than in vacuo, whereas for γL it ranges from 100% to 400% depending upon the nonlinear optical process and the length of the PA chain. These solvent-induced αL and γL enhancements can partially be accounted for by the corresponding decrease of the energy of the lowest optically-allowed electronic excitation. The geometrical parameters of the ground state of the PA chains are almost unaffected by the solvent. This shows that the solvent effects are mainly of electronic nature. In addition, the local field factors, which relate the macroscopic or Maxwell field to the field experienced by the solute, tend towards unity with increasing chain length for the longitudinal PA axis.

Lid opening and conformational stability of T1 Lipase is mediated by increasing chain length polar solvents

PubMed Central

Mohamad Ali, Mohd Shukuri; Salleh, Abu Bakar; Rahman, Raja Noor Zaliha Raja Abd; Normi, Yahaya M.; Mohd Shariff, Fairolniza

2017-01-01

The dynamics and conformational landscape of proteins in organic solvents are events of potential interest in nonaqueous process catalysis. Conformational changes, folding transitions, and stability often correspond to structural rearrangements that alter contacts between solvent molecules and amino acid residues. However, in nonaqueous enzymology, organic solvents limit stability and further application of proteins. In the present study, molecular dynamics (MD) of a thermostable Geobacillus zalihae T1 lipase was performed in different chain length polar organic solvents (methanol, ethanol, propanol, butanol, and pentanol) and water mixture systems to a concentration of 50%. On the basis of the MD results, the structural deviations of the backbone atoms elucidated the dynamic effects of water/organic solvent mixtures on the equilibrium state of the protein simulations in decreasing solvent polarity. The results show that the solvent mixture gives rise to deviations in enzyme structure from the native one simulated in water. The drop in the flexibility in H2O, MtOH, EtOH and PrOH simulation mixtures shows that greater motions of residues were influenced in BtOH and PtOH simulation mixtures. Comparing the root mean square fluctuations value with the accessible solvent area (SASA) for every residue showed an almost correspondingly high SASA value of residues to high flexibility and low SASA value to low flexibility. The study further revealed that the organic solvents influenced the formation of more hydrogen bonds in MtOH, EtOH and PrOH and thus, it is assumed that increased intraprotein hydrogen bonding is ultimately correlated to the stability of the protein. However, the solvent accessibility analysis showed that in all solvent systems, hydrophobic residues were exposed and polar residues tended to be buried away from the solvent. Distance variation of the tetrahedral intermediate packing of the active pocket was not conserved in organic solvent systems, which could lead to weaknesses in the catalytic H-bond network and most likely a drop in catalytic activity. The conformational variation of the lid domain caused by the solvent molecules influenced its gradual opening. Formation of additional hydrogen bonds and hydrophobic interactions indicates that the contribution of the cooperative network of interactions could retain the stability of the protein in some solvent systems. Time-correlated atomic motions were used to characterize the correlations between the motions of the atoms from atomic coordinates. The resulting cross-correlation map revealed that the organic solvent mixtures performed functional, concerted, correlated motions in regions of residues of the lid domain to other residues. These observations suggest that varying lengths of polar organic solvents play a significant role in introducing dynamic conformational diversity in proteins in a decreasing order of polarity. PMID:28533982

Effects of solvent concentration and composition on protein dynamics: 13C MAS NMR studies of elastin in glycerol-water mixtures.

PubMed

Demuth, Dominik; Haase, Nils; Malzacher, Daniel; Vogel, Michael

2015-08-01

We use (13)C CP MAS NMR to investigate the dependence of elastin dynamics on the concentration and composition of the solvent at various temperatures. For elastin in pure glycerol, line-shape analysis shows that larger-scale fluctuations of the protein backbone require a minimum glycerol concentration of ~0.6 g/g at ambient temperature, while smaller-scale fluctuations are activated at lower solvation levels of ~0.2 g/g. Immersing elastin in various glycerol-water mixtures, we observe at room temperature that the protein mobility is higher for lower glycerol fractions in the solvent and, thus, lower solvent viscosity. When decreasing the temperature, the elastin spectra approach the line shape for the rigid protein at 245 K for all studied samples, indicating that the protein ceases to be mobile on the experimental time scale of ~10(-5) s. Our findings yield evidence for a strong coupling between elastin fluctuations and solvent dynamics and, hence, such interaction is not restricted to the case of protein-water mixtures. Spectral resolution of different carbon species reveals that the protein-solvent couplings can, however, be different for side chain and backbone units. We discuss these results against the background of the slaving model for protein dynamics. Copyright © 2015 Elsevier B.V. All rights reserved.

12. FIRST FLOOR BLD 28B: DETAIL SOLVENT PUMPS. Fafnir ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

12. FIRST FLOOR BLD 28B: DETAIL SOLVENT PUMPS. - Fafnir Bearing Plant, Bounded on North side by Myrtle Street, on South side by Orange Street, on East side by Booth Street & on West side by Grove Street, New Britain, Hartford County, CT

The Viscoelastic Properties of Nematic Monodomains Containing Liquid Crystal Polymers.

NASA Astrophysics Data System (ADS)

Gu, Dongfeng

The work presented here investigates the viscoelastic properties of nematic materials containing liquid crystal polymers (LCP). We focus on how the elastic constants and the viscosity coefficients of the mixture systems are influenced by polymer architectures. In dynamic light scattering studies of the relaxation of the director orientation fluctuations for the splay, twist, and bend deformation modes, decrease of the relaxation rates was observed when LCPs were dissolved into low molar mass nematics (LMMN). For the side-chain LCPs, the slowing down in the bend mode is comparable to or larger than those of the splay and twist modes. For main-chain LCPs, the relative changes in the relaxation rates for the twist and splay modes are about one order of magnitude larger than that for the bend mode. The results of light scattering under an electric field show that the decrease in the twist relaxation rate is due to a large increase in the twist viscosity and a minor decrease in the twist elastic constant. These changes were found to increase with decrease of the spacer length, with increase of molecular weight, and with decrease of the backbone flexibility. In Freedericksz transition measurements, the splay and bend elastic constants and the dielectric anisotropies of the nematic mixtures were determined and the values are 5~15% lower than those of the pure solvent. From the analysis of the results of Freedericksz transition and light scattering experiments, a complete set of the elastic constants and viscosity coefficients corresponding to the three director deformation modes were obtained for the LCP mixtures. The changes in the viscosity coefficients due to addition of LCPs were analysed to estimate the anisotropic shapes of the polymer backbone via a hydrodynamic model. The results suggest that an oblate backbone configuration is maintained by the side-chain LCPs and a prolate chain configuration appears for the main-chain LCPs. The rheological behavior of a side-chain and a main-chain LCP nematic solutions were investigated. The addition of the side-chain LCP into a flow-aligning LMMN (5CB) induces director tumbling in the mixture, and, the dissolution of the main-chain LCP into a director tumbling LMMN (8CB) makes the solution become a flow-aligning nematic. Based on the hydrodynamic theory, these observations are further confirmation of the chain anisotropies of the LCPs investigated. Ericksen's transversely isotropic fluid model was used to extract the various viscosity coefficients with good accuracy. In addition, we believe that this is the first time the bulk rheological consequences of director tumbling in LMMNs has been observed.

Hydrophobic core malleability of a de novo designed three-helix bundle protein.

PubMed

Walsh, S T; Sukharev, V I; Betz, S F; Vekshin, N L; DeGrado, W F

2001-01-12

De novo protein design provides a tool for testing the principles that stabilize the structures of proteins. Recently, we described the design and structure determination of alpha(3)D, a three-helix bundle protein with a well-packed hydrophobic core. Here, we test the malleability and adaptability of this protein's structure by mutating a small, Ala residue (A60) in its core to larger, hydrophobic side-chains, Leu and Ile. Such changes introduce strain into the structures of natural proteins, and therefore generally destabilize the native state. By contrast, these mutations were slightly stabilizing ( approximately 1.5 kcal mol(-1)) to the tertiary structure of alpha(3)D. The value of DeltaC(p) for unfolding of these mutants was not greatly affected relative to wild-type, indicating that the change in solvent accessibility for unfolding was similar. However, two-dimensional heteronuclear single quantum coherence spectra indicate that the protein adjusts to the introduction of steric bulk in different ways. A60L-alpha(3)D showed serious erosion in the dispersion of both the amide backbone as well as the side-chain methyl chemical shifts. By contrast, A60I-alpha(3)D showed excellent dispersion of the backbone resonances, and selective changes in dispersion of the aliphatic side-chains proximal to the site of mutation. Together, these data suggest that alpha(3)D, although folded into a unique three-dimensional structure, is nevertheless more malleable and flexible than most natural, native proteins. Copyright 2001 Academic Press.

A neurological evaluation of workers exposed to mixtures of organic solvents.

PubMed Central

Maizlish, N A; Fine, L J; Albers, J W; Whitehead, L; Langolf, G D

1987-01-01

Workers with long term exposure to mixtures of organic solvents below regulatory limits have been reported to experience mild, but clinically detectable, sensory or sensorimotor polyneuropathies. In conjuction with a cross sectional study of behavioural performance a clinical neurological evaluation was conducted among printers and spray painters to examine dose response relations. All 240 subjects completed an occupational history and symptom questionnaire and underwent a clinical neurological examination. On average, subjects had been employed on their current job for six years. Classification of solvent exposure for each subject was based on exposed versus non-exposed job titles and observations during an industrial hygiene walk-through or on the measured concentration of solvents in full shift personal air samples. The average full shift solvent concentration was 302 ppm for printing plant workers and 6-13 ppm for workers at other plants. Isopropanol and hexane were the major constituents. Neurological abnormalities consistent with mild polyneuropathy were found in 16% of subjects; none was clinically significant. Exposed/non-exposed comparisons showed slightly higher frequency of symptoms in the exposed subjects which was not related to solvent level. Subjects categorised as exposed during the walk- through survey also had poorer vibratory sensation measured at the foot and diminished ankle reflexes. In multiple linear regression models, however, controlling for age, sex, alcohol intake, and examiner, no significant (p less than 0.05) relation was found between solvent concentration and poor neurological function except for two point discrimination measured at the foot. This investigation has not provided evidence for dose related adverse neurological effects from exposure to moderately low levels of solvent mixtures for a relatively short duration, although this may be due to the shortness of exposure duration, the type of solvent exposure, or to selection factors. PMID:3814530

Regimes of electrostatic collapse of a highly charged polyelectrolyte in a poor solvent.

PubMed

Tom, Anvy Moly; Vemparala, Satyavani; Rajesh, R; Brilliantov, Nikolai V

2017-03-01

We perform extensive molecular dynamics simulations of a highly charged, collapsed, flexible polyelectrolyte chain in a poor solvent for the case when the electrostatic interactions, characterized by the reduced Bjerrum length l B , are strong. We find the existence of several sub-regimes in the dependence of the gyration radius of the chain R g on l B characterized by R g ∼ l. In contrast to a good solvent, the exponent γ for a poor solvent crucially depends on the size and valency of the counterions. To explain the different sub-regimes, we generalize the existing counterion fluctuation theory by including a more complete account of all possible volume interactions in the free energy of the polyelectrolyte chain. We also show that the presence of condensed counterions modifies the effective attraction among the chain monomers and modulates the sign of the second virial coefficient under poor solvent conditions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Driscoll, P.C.; Gronenborn, A.M.; Beress, L.

The three-dimensional solution structure of the antihypertensive and antiviral protein BDS-I from the sea anemone Anemonia sulcata has been determined on the basis of 489 interproton and 24 hydrogen-bonding distance restraints supplemented by 23 {phi} backbone and 21 {sub {chi}1} side-chain torsion angle restraints derived from nuclear magnetic resonance (NMR) measurements. A total of 42 structures is calculated by a hybrid metric matrix distance geometry-dynamical simulated annealing approach. Both the backbone and side-chain atom positions are well defined. The average atomic rms difference between the 42 individual SA structures and the mean structure obtained by averaging their coordinates is 0.67more » {plus minus} 0.12 {angstrom} for the backbone atoms and 0.90 {plus minus} 0.17 {angstrom} for all atoms. The core of the protein is formed by a triple-stranded antiparallel {beta}-sheet composed of residues 14-16 (strand 1), 30-34 (strand 2), and 37-41 (strand 3) with an additional mini-antiparallel {beta}-sheet at the N-terminus (residues 6-9). The first and second strands of the triple-stranded antiparallel {beta}-sheet are connected by a long exposed loop. A number of side-chain interactions are discussed in light of the structure.« less

tRNA acceptor stem and anticodon bases form independent codes related to protein folding

PubMed Central

Carter, Charles W.; Wolfenden, Richard

2015-01-01

Aminoacyl-tRNA synthetases recognize tRNA anticodon and 3′ acceptor stem bases. Synthetase Urzymes acylate cognate tRNAs even without anticodon-binding domains, in keeping with the possibility that acceptor stem recognition preceded anticodon recognition. Representing tRNA identity elements with two bits per base, we show that the anticodon encodes the hydrophobicity of each amino acid side-chain as represented by its water-to-cyclohexane distribution coefficient, and this relationship holds true over the entire temperature range of liquid water. The acceptor stem codes preferentially for the surface area or size of each side-chain, as represented by its vapor-to-cyclohexane distribution coefficient. These orthogonal experimental properties are both necessary to account satisfactorily for the exposed surface area of amino acids in folded proteins. Moreover, the acceptor stem codes correctly for β-branched and carboxylic acid side-chains, whereas the anticodon codes for a wider range of such properties, but not for size or β-branching. These and other results suggest that genetic coding of 3D protein structures evolved in distinct stages, based initially on the size of the amino acid and later on its compatibility with globular folding in water. PMID:26034281

Extended Hansen solubility approach: naphthalene in individual solvents.

PubMed

Martin, A; Wu, P L; Adjei, A; Beerbower, A; Prausnitz, J M

1981-11-01

A multiple regression method using Hansen partial solubility parameters, delta D, delta p, and delta H, was used to reproduce the solubilities of naphthalene in pure polar and nonpolar solvents and to predict its solubility in untested solvents. The method, called the extended Hansen approach, was compared with the extended Hildebrand solubility approach and the universal-functional-group-activity-coefficient (UNIFAC) method. The Hildebrand regular solution theory was also used to calculate naphthalene solubility. Naphthalene, an aromatic molecule having no side chains or functional groups, is "well-behaved', i.e., its solubility in active solvents known to interact with drug molecules is fairly regular. Because of its simplicity, naphthalene is a suitable solute with which to initiate the difficult study of solubility phenomena. The three methods tested (Hildebrand regular solution theory was introduced only for comparison of solubilities in regular solution) yielded similar results, reproducing naphthalene solubilities within approximately 30% of literature values. In some cases, however, the error was considerably greater. The UNIFAC calculation is superior in that it requires only the solute's heat of fusion, the melting point, and a knowledge of chemical structures of solute and solvent. The extended Hansen and extended Hildebrand methods need experimental solubility data on which to carry out regression analysis. The extended Hansen approach was the method of second choice because of its adaptability to solutes and solvents from various classes. Sample calculations are included to illustrate methods of predicting solubilities in untested solvents at various temperatures. The UNIFAC method was successful in this regard.

11. FIRST FLOOR BLDG. 28B: OVERVIEW SOLVENT PUMPS AND HEATING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

11. FIRST FLOOR BLDG. 28B: OVERVIEW SOLVENT PUMPS AND HEATING LOOKING WEST. - Fafnir Bearing Plant, Bounded on North side by Myrtle Street, on South side by Orange Street, on East side by Booth Street & on West side by Grove Street, New Britain, Hartford County, CT

Cyclo-hexa-peptides at the water/cyclohexane interface: a molecular dynamics simulation.

PubMed

Cen, Min; Fan, Jian Fen; Liu, Dong Yan; Song, Xue Zeng; Liu, Jian; Zhou, Wei Qun; Xiao, He Ming

2013-02-01

Molecular dynamic (MD) simulations have been performed to study the behaviors of ten kinds of cyclo-hexa-peptides (CHPs) composed of amino acids with the diverse hydrophilic/hydrophobic side chains at the water/cyclohexane interface. All the CHPs take the "horse-saddle" conformations at the interface and the hydrophilicity/hydrophobicity of the side chains influences the backbones' structural deformations. The orientations and distributions of the CHPs at the interface and the differences of interaction energies (ΔΔE) between the CHPs and the two liquid phases have been determined. RDF analysis shows that the H-bonds were formed between the O(C) atoms of the CHPs' backbones and H(w) atoms of water molecules. N atoms of the CHPs' backbones formed the H-bonds or van der Waals interactions with the water solvent. It was found that there is a parallel relationship between ΔΔE and the lateral diffusion coefficients (D ( xy )) of the CHPs at the interface. The movements of water molecules close to the interface are confined to some extent, indicating that the dynamics of the CHPs and interfacial water molecules are strongly coupled.

Charge transfer in model peptides: obtaining Marcus parameters from molecular simulation.

PubMed

Heck, Alexander; Woiczikowski, P Benjamin; Kubař, Tomáš; Giese, Bernd; Elstner, Marcus; Steinbrecher, Thomas B

2012-02-23

Charge transfer within and between biomolecules remains a highly active field of biophysics. Due to the complexities of real systems, model compounds are a useful alternative to study the mechanistic fundamentals of charge transfer. In recent years, such model experiments have been underpinned by molecular simulation methods as well. In this work, we study electron hole transfer in helical model peptides by means of molecular dynamics simulations. A theoretical framework to extract Marcus parameters of charge transfer from simulations is presented. We find that the peptides form stable helical structures with sequence dependent small deviations from ideal PPII helices. We identify direct exposure of charged side chains to solvent as a cause of high reorganization energies, significantly larger than typical for electron transfer in proteins. This, together with small direct couplings, makes long-range superexchange electron transport in this system very slow. In good agreement with experiment, direct transfer between the terminal amino acid side chains can be dicounted in favor of a two-step hopping process if appropriate bridging groups exist. © 2012 American Chemical Society

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olsen, Brett N.; Schlesinger, Paul H.; Ory, Daniel S.

Side-chain oxysterols are enzymatically generated oxidation products of cholesterol that serve a central role in mediating cholesterol homeostasis. Recent work has shown that side-chain oxysterols, such as 25-hydroxycholesterol (25-HC), alter membrane structure in very different ways from cholesterol, suggesting a possible mechanism for how these oxysterols regulate cholesterol homeostasis. Here we extend our previous work, using molecular dynamics simulations of 25-HC and cholesterol mixtures in 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayers to examine interactions between 25-HC and cholesterol in the same bilayer. When added to cholesterol-containing membranes, 25-HC causes larger changes in membrane structure than when added to cholesterol-free membranes, demonstrating interactions betweenmore » the two sterols. We also find that the presence of 25-HC changes the position, orientation, and solvent accessibility of cholesterol, shifting it into the water interface and therefore its availability to external acceptors. This is consistent with experimental results showing that oxysterols can trigger cholesterol trafficking from the plasma membrane to the endoplasmic reticulum. These interactions provide a potential mechanism for 25-HC-mediated regulation of cholesterol trafficking and homeostasis through direct modulation of cholesterol availability.« less

Exacerbation of noise-induced hearing loss by co-exposure to workplace chemicals.

PubMed

Sliwinska-Kowalska, Mariola; Zamyslowska-Szmytke, Ewa; Szymczak, Wieslaw; Kotylo, Piotr; Fiszer, Marta; Wesolowski, Wiktor; Pawlaczyk-Luszczynska, Malgorzata

2005-05-01

: Numerous organic solvents applied in industry, like toluene, styrene, xylene and n-hexane have been demonstrated to impair hearing in animals. However, the effects of exposure to a given organic solvent and the interaction of noise and solvents on hearing in humans are still not fully recognized. : The study was aimed to assess the effects of occupational exposure to solvents alone or in combination with noise on hearing in 1117 employees of yacht, ship, plastic, shoe, and paint and lacquer industry. These persons were exposed either to the mixture of organic solvents with xylene as the main component, or predominantly to styrene, or to the mixture of n-hexane and toluene. Detailed questionnaire data and pure-tone audiometry were compared with data of the reference group that included white collar workers, exposed neither to solvents nor noise and metal factory workers exposed to noise only. In all statistics, the confounding factors were recognized as gender, age, exposure to noise, and other variables occurring at a different rate in study and reference group. : Odds ratio (OR) of hearing loss related with the particular exposure to chemicals was 2.4 (95%CI 1.59-3.74) in case of solvent mixture, 3.9 (95%CI 2.4-6.2) in case of styrene and 5.3 (95%CI 2.6-10.9) in case of n-hexane and toluene exposure. The odds of developing hearing loss substantially increased in the case of combined exposure to organic solvents and noise as compared to isolated exposure to each of these hazards. The highest OR (over 20-fold) was demonstrated in subgroups of subjects exposed simultaneously to noise and two ototoxic solvents (i.e. styrene and toluene or n-hexane and toluene). The mean hearing thresholds were significantly higher in the solvent-exposed groups than in the reference group. The differences in thresholds were observed at high frequencies in the solvent mixture- and n-hexane + toluene-exposed groups and at all frequencies in the styrene-exposed group. A positive linear relationship existed between exposure to solvents and hearing thresholds at high frequencies. : The results of the study provide the epidemiological evidence that exposure to organic solvents in humans is associated with an increased risk of hearing loss. The simultaneous exposure to organic solvents and noise seems to enhance the hearing deficit if compared with isolated exposures.

Hydration of amino acids: FTIR spectra and molecular dynamics studies.

PubMed

Panuszko, Aneta; Adamczak, Beata; Czub, Jacek; Gojło, Emilia; Stangret, Janusz

2015-11-01

The hydration of selected amino acids, alanine, glycine, proline, valine, isoleucine and phenylalanine, has been studied in aqueous solutions by means of FTIR spectra of HDO isotopically diluted in H2O. The difference spectra procedure and the chemometric method have been applied to remove the contribution of bulk water and thus to separate the spectra of solute-affected HDO. To support interpretation of obtained spectral results, molecular dynamics simulations of amino acids were performed. The structural-energetic characteristic of these solute-affected water molecules shows that, on average, water affected by amino acids forms stronger and shorter H-bonds than those in pure water. Differences in the influence of amino acids on water structure have been noticed. The effect of the hydrophobic side chain of an amino acid on the solvent interactions seems to be enhanced because of the specific cooperative coupling of water strong H-bond chain, connecting the carboxyl and amino groups, with the clathrate-like H-bond network surrounding the hydrocarbon side chain. The parameter derived from the spectral data, which corresponds to the contributions of the population of weak hydrogen bonds of water molecules which have been substituted by the stronger ones in the hydration sphere of amino acids, correlated well with the amino acid hydrophobicity indexes.

Strong liquid-crystalline polymeric compositions

DOEpatents

Dowell, Flonnie

1993-01-01

Strong liquid-crystalline polymeric (LCP) compositions of matter. LCP backbones are combined with liquid crystalline (LC) side chains in a manner which maximizes molecular ordering through interdigitation of the side chains, thereby yielding materials which are predicted to have superior mechanical properties over existing LCPs. The theoretical design of LCPs having such characteristics includes consideration of the spacing distance between side chains along the backbone, the need for rigid sections in the backbone and in the side chains, the degree of polymerization, the length of the side chains, the regularity of the spacing of the side chains along the backbone, the interdigitation of side chains in sub-molecular strips, the packing of the side chains on one or two sides of the backbone to which they are attached, the symmetry of the side chains, the points of attachment of the side chains to the backbone, the flexibility and size of the chemical group connecting each side chain to the backbone, the effect of semiflexible sections in the backbone and the side chains, and the choice of types of dipolar and/or hydrogen bonding forces in the backbones and the side chains for easy alignment.

[Evaluation of exposure of auto painters to organic solvents in the city of Bogota].

PubMed

Palma, Marien; Briceño, Leonardo; Idrovo, Álvaro J; Varona, Marcela

2015-08-01

Painters of automobiles are exposed to pure and mixed solvents that have been associated with neurological effects and carcinogenic mutations. To characterize the health and work conditions of individuals who are occupationally exposed to organic solvents used in sheet metal and auto body shops in Bogota. Descriptive, cross-sectional study that characterizes the health and work conditions of individuals exposed to organic solvents in sheet metal and auto body shops in Bogota. A group exposed to the solvents was compared to an unexposed group. Air concentrations of benzene, toluene and xylene (BTX) were determined, individual questionnaires were administered and phenylmercapturic, hippuric and ortho- and para-methylhippuric acids were measured in urine. The results of the measurements and the questionnaires were correlated to determine the exposure panorama. For the three BTX metabolites, statistically significant differences (p<0.001) were found between the population exposed to the solvents and the unexposed population. For the exposed population, positive correlations were found between toluene in air and hippuric acid in urine (rho=0.82) and between xylene in air and o-methylhippuric acid in urine (rho=0.76). Hippuric acid values exceeded permissible levels in 11 workers and p-methylhippuric acid exceeded permissible levels in 8 workers. None of the phenylmercapturic values exceeded the limit. Auto painters are exposed to high levels of organic solvents at the workplace and do not have adequate industrial health and safety conditions to perform their jobs.

Work ability score of solvent-exposed workers.

PubMed

Furu, Heidi; Sainio, Markku; Hyvärinen, Hanna-Kaisa; Kaukiainen, Ari

2018-03-28

Occupational chronic solvent encephalopathy (CSE), characterized by neurocognitive dysfunction, often leads to early retirement. However, only the more severe cases are diagnosed with CSE, and little is known about the work ability of solvent-exposed workers in general. The aim was to study memory and concentration symptoms, work ability and the effect of both solvent-related and non-occupational factors on work ability, in an actively working solvent-exposed population. A questionnaire on exposure and health was sent to 3640 workers in four solvent-exposed fields, i.e. painters and floor-layers, boat builders, printers, and metal workers. The total number of responses was 1730. We determined the work ability score (WAS), a single question item of the Work Ability Index, and studied solvent exposure, demographic factors, Euroquest memory and concentration symptoms, chronic diseases, and employment status using univariate and multivariate analyses. The findings were compared to those of a corresponding national blue-collar reference population (n = 221), and a small cohort of workers with CSE (n = 18). The proportion of workers with memory and concentration symptoms was significantly associated with solvent exposure. The WAS of solvent-exposed workers was lower than that of the national blue-collar reference group, and the difference was significant in the oldest age group (those aged over 60). Solvent-exposed worker's WAS were higher than those of workers diagnosed with CSE. The WAS were lowest among painters and floor-layers, followed by metal workers and printers, and highest among boat builders. The strongest explanatory factors for poor work ability were the number of chronic diseases, age and employment status. Solvent exposure was a weak independent risk factor for reduced WAS, comparable to a level of high alcohol consumption. Even if memory and concentration symptoms were associated with higher solvent exposure, the effect of solvents on self-experienced work ability was relatively weak. This in line with the improved occupational hygiene and reduced solvent exposure levels in industrialized countries, thus the effect may be stronger in high-level exposure environments. As a single question, WAS is easily included, applicable, and recommendable in occupational screening questionnaires.

Quantifying protein interface footprinting by hydroxyl radical oxidation and molecular dynamics simulation: application to galectin-1.

PubMed

Charvátová, Olga; Foley, B Lachele; Bern, Marshall W; Sharp, Joshua S; Orlando, Ron; Woods, Robert J

2008-11-01

Biomolecular surface mapping methods offer an important alternative method for characterizing protein-protein and protein-ligand interactions in cases in which it is not possible to determine high-resolution three-dimensional (3D) structures of complexes. Hydroxyl radical footprinting offers a significant advance in footprint resolution compared with traditional chemical derivatization. Here we present results of footprinting performed with hydroxyl radicals generated on the nanosecond time scale by laser-induced photodissociation of hydrogen peroxide. We applied this emerging method to a carbohydrate-binding protein, galectin-1. Since galectin-1 occurs as a homodimer, footprinting was employed to characterize the interface of the monomeric subunits. Efficient analysis of the mass spectrometry data for the oxidized protein was achieved with the recently developed ByOnic (Palo Alto, CA) software that was altered to handle the large number of modifications arising from side-chain oxidation. Quantification of the level of oxidation has been achieved by employing spectral intensities for all of the observed oxidation states on a per-residue basis. The level of accuracy achievable from spectral intensities was determined by examination of mixtures of synthetic peptides related to those present after oxidation and tryptic digestion of galectin-1. A direct relationship between side-chain solvent accessibility and level of oxidation emerged, which enabled the prediction of the level of oxidation given the 3D structure of the protein. The precision of this relationship was enhanced through the use of average solvent accessibilities computed from 10 ns molecular dynamics simulations of the protein.

Effect of sequence and stereochemistry reversal on p53 peptide mimicry.

PubMed

Atzori, Alessio; Baker, Audrey E; Chiu, Mark; Bryce, Richard A; Bonnet, Pascal

2013-01-01

Peptidomimetics effective in modulating protein-protein interactions and resistant to proteolysis have potential in therapeutic applications. An appealing yet underperforming peptidomimetic strategy is to employ D-amino acids and reversed sequences to mimic a lead peptide conformation, either separately or as the combined retro-inverso peptide. In this work, we examine the conformations of inverse, reverse and retro-inverso peptides of p53(15-29) using implicit solvent molecular dynamics simulation and circular dichroism spectroscopy. In order to obtain converged ensembles for the peptides, we find enhanced sampling is required via the replica exchange molecular dynamics method. From these replica exchange simulations, the D-peptide analogues of p53(15-29) result in a predominantly left-handed helical conformation. When the parent sequence is reversed sequence as either the L-peptide and D-peptide, these peptides display a greater helical propensity, feature reflected by NMR and CD studies in TFE/water solvent. The simulations also indicate that, while approximately similar orientations of the side-chains are possible by the peptide analogues, their ability to mimic the parent peptide is severely compromised by backbone orientation (for D-amino acids) and side-chain orientation (for reversed sequences). A retro-inverso peptide is disadvantaged as a mimic in both aspects, and further chemical modification is required to enable this concept to be used fruitfully in peptidomimetic design. The replica exchange molecular simulation approach adopted here, with its ability to provide detailed conformational insights into modified peptides, has potential as a tool to guide structure-based design of new improved peptidomimetics.

Strong liquid-crystalline polymeric compositions

DOEpatents

Dowell, F.

1993-12-07

Strong liquid-crystalline polymeric (LCP) compositions of matter are described. LCP backbones are combined with liquid crystalline (LC) side chains in a manner which maximizes molecular ordering through interdigitation of the side chains, thereby yielding materials which are predicted to have superior mechanical properties over existing LCPs. The theoretical design of LCPs having such characteristics includes consideration of the spacing distance between side chains along the backbone, the need for rigid sections in the backbone and in the side chains, the degree of polymerization, the length of the side chains, the regularity of the spacing of the side chains along the backbone, the interdigitation of side chains in sub-molecular strips, the packing of the side chains on one or two sides of the backbone to which they are attached, the symmetry of the side chains, the points of attachment of the side chains to the backbone, the flexibility and size of the chemical group connecting each side chain to the backbone, the effect of semiflexible sections in the backbone and the side chains, and the choice of types of dipolar and/or hydrogen bonding forces in the backbones and the side chains for easy alignment. 27 figures.

Psychophysical Evaluation of Achromatic and Chromatic Vision of Workers Chronically Exposed to Organic Solvents

PubMed Central

Lacerda, Eliza Maria da Costa Brito; Lima, Monica Gomes; Rodrigues, Anderson Raiol; Teixeira, Cláudio Eduardo Correa; de Lima, Lauro José Barata; Ventura, Dora Fix; Silveira, Luiz Carlos de Lima

2012-01-01

The purpose of this paper was to evaluate achromatic and chromatic vision of workers chronically exposed to organic solvents through psychophysical methods. Thirty-one gas station workers (31.5 ± 8.4 years old) were evaluated. Psychophysical tests were achromatic tests (Snellen chart, spatial and temporal contrast sensitivity, and visual perimetry) and chromatic tests (Ishihara's test, color discrimination ellipses, and Farnsworth-Munsell 100 hue test—FM100). Spatial contrast sensitivities of exposed workers were lower than the control at spatial frequencies of 20 and 30 cpd whilst the temporal contrast sensitivity was preserved. Visual field losses were found in 10–30 degrees of eccentricity in the solvent exposed workers. The exposed workers group had higher error values of FM100 and wider color discrimination ellipses area compared to the controls. Workers occupationally exposed to organic solvents had abnormal visual functions, mainly color vision losses and visual field constriction. PMID:22220188

Sleep disturbances and exposure to organic solvents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lindelof, B.; Almkvist, O.; Goethe, C.

An inquiry about sleep habits and sleep disturbances revealed a significantly higher prevalence of insomnia in a solvent-exposed group than in a comparable group that had no occupational exposure to organic solvents. The solvent-exposed group has also registered an increased consumption of hypnotics, and a significant increase occurred in the number of individuals who had consulted physicians because of sleep disorders. The results indicate that solvent exposure could induce sleep disturbances.

The Crystal Structure of the Ring-Hydroxylating Dioxygenase from Sphingomonas CHY-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jakoncic,J.; Jouanneau, Y.; Meyer, C.

The ring-hydroxylating dioxygenase (RHD) from Sphingomonas CHY-1 is remarkable due to its ability to initiate the oxidation of a wide range of polycyclic aromatic hydrocarbons (PAHs), including PAHs containing four- and five-fused rings, known pollutants for their toxic nature. Although the terminal oxygenase from CHY-1 exhibits limited sequence similarity with well characterized RHDs from the naphthalene dioxygenase family, the crystal structure determined to 1.85 {angstrom} by molecular replacement revealed the enzyme to share the same global {alpha}{sub 3}{beta}{sub 3} structural pattern. The catalytic domain distinguishes itself from other bacterial non-heme Rieske iron oxygenases by a substantially larger hydrophobic substrate bindingmore » pocket, the largest ever reported for this type of enzyme. While residues in the proximal region close to the mononuclear iron atom are conserved, the central region of the catalytic pocket is shaped mainly by the side chains of three amino acids, Phe350, Phe404 and Leu356, which contribute to the rather uniform trapezoidal shape of the pocket. Two flexible loops, LI and LII, exposed to the solvent seem to control the substrate access to the catalytic pocket and control the pocket length. Compared with other naphthalene dioxygenases residues Leu223 and Leu226, on loop LI, are moved towards the solvent, thus elongating the catalytic pocket by at least 2 {angstrom}. An 11 {angstrom} long water channel extends from the interface between the {alpha} and {beta} subunits to the catalytic site. The comparison of these structures with other known oxygenases suggests that the broad substrate specificity presented by the CHY-1 oxygenase is primarily due to the large size and particular topology of its catalytic pocket and provided the basis for the study of its reaction mechanism.« less

Gating by tryptophan 73 exposes a cryptic pocket at the protein-binding interface of the oncogenic eIF4E protein.

PubMed

Lama, Dilraj; Brown, Christopher J; Lane, David P; Verma, Chandra S

2015-10-27

Targeting protein-protein interacting sites for potential therapeutic applications is a challenge in the development of inhibitors, and this becomes more difficult when these interfaces are relatively planar, as in the eukaryotic translation initiation factor 4E (eIF4E) protein. eIF4E is an oncogene that is overexpressed in numerous forms of cancer, making it a prime target as a therapeutic molecule. We report here the presence of a cryptic pocket at the protein-binding interface of eIF4E, which opens transiently during molecular dynamics simulations of the protein in solvent water and is observed to be stable when solvent water is mixed with benzene molecules. This pocket can also be seen in the ensemble of structures available from the solution-state conformations of eIF4E. The accessibility of the pocket is gated by the side-chain transitions of an evolutionarily conserved tryptophan residue. It is found to be feasible for accommodating clusters of benzene molecules, which signify the plasticity and ligandability of the pocket. We also observe that the newly formed cavity provides a favorable binding environment for interaction of a well-recognized small molecule inhibitor of eIF4E. The occurrence of this transiently accessible cavity highlights the existence of a more pronounced binding groove in a region that has traditionally been considered to be planar. Together, the data suggest that an alternate binding cavity exists on eIF4E and could be exploited for the rational design and development of a new class of lead compounds against the protein.

Dissolution of covalent adaptable network polymers in organic solvent

NASA Astrophysics Data System (ADS)

Yu, Kai; Yang, Hua; Dao, Binh H.; Shi, Qian; Yakacki, Christopher M.

2017-12-01

It was recently reported that thermosetting polymers can be fully dissolved in a proper organic solvent utilizing a bond-exchange reaction (BER), where small molecules diffuse into the polymer, break the long polymer chains into short segments, and eventually dissolve the network when sufficient solvent is provided. The solvent-assisted dissolution approach was applied to fully recycle thermosets and their fiber composites. This paper presents the first multi-scale modeling framework to predict the dissolution kinetics and mechanics of thermosets in organic solvent. The model connects the micro-scale network dynamics with macro-scale material properties: in the micro-scale, a model is developed based on the kinetics of BERs to describe the cleavage rate of polymer chains and evolution of chain segment length during the dissolution. The micro-scale model is then fed into a continuum-level model with considerations of the transportation of solvent molecules and chain segments in the system. The model shows good prediction on conversion rate of functional groups, degradation of network mechanical properties, and dissolution rate of thermosets during the dissolution. It identifies the underlying kinetic factors governing the dissolution process, and reveals the influence of different material and processing variables on the dissolution process, such as time, temperature, catalyst concentration, and chain length between cross-links.

Adsorption of flexible polymer chains on a surface: Effects of different solvent conditions

NASA Astrophysics Data System (ADS)

Martins, P. H. L.; Plascak, J. A.; Bachmann, M.

2018-05-01

Polymer chains undergoing a continuous adsorption-desorption transition are studied through extensive computer simulations. A three-dimensional self-avoiding walk lattice model of a polymer chain grafted onto a surface has been treated for different solvent conditions. We have used an advanced contact-density chain-growth algorithm, in which the density of contacts can be directly obtained. From this quantity, the order parameter and its fourth-order Binder cumulant are computed, as well as the corresponding critical exponents and the adsorption-desorption transition temperature. As the number of configurations with a given number of surface contacts and monomer-monomer contacts is independent of the temperature and solvent conditions, it can be easily applied to get results for different solvent parameter values without the need of any extra simulations. In analogy to continuous magnetic phase transitions, finite-size-scaling methods have been employed. Quite good results for the critical properties and phase diagram of very long single polymer chains have been obtained by properly taking into account the effects of corrections to scaling. The study covers all solvent effects, going from the limit of super-self-avoiding walks, characterized by effective monomer-monomer repulsion, to poor solvent conditions that enable the formation of compact polymer structures.

Combined effects of exposure to occupational noise and mixed organic solvents on blood pressure in car manufacturing company workers.

PubMed

Attarchi, Mirsaeed; Golabadi, Majid; Labbafinejad, Yasser; Mohammadi, Saber

2013-02-01

Recent studies suggest that occupational exposures such as noise and organic solvents may affect blood pressure. The aim of this study was to investigate interaction of noise and mixed organic solvents on blood pressure. Four hundred seventy-one workers of a car manufacturing plant were divided into four groups: group one or G1 workers exposed to noise and mixed organic solvents in the permitted limit or control group, G3 exposed to noise only, G2 exposed to solvents only, and G4 workers exposed to noise and mixed organic solvents at higher than the permitted limit or co-exposure group. Biological interaction of two variables on hypertension was calculated using the synergistic index. The workers of co-exposure group (G4), noise only group (G3), and solvents only group (G2) had significantly higher mean values of SBP and DBP than workers of control group (G1) or office workers (P < 0.05). Also logistic regression analysis showed a significant association between hypertension and exposure to noise and mixture of organic solvents. Odds ratio for hypertension in the co-exposure group and the noise only and solvents only exposed groups was 14.22, 9.43, and 4.38, respectively, compared to control group. In this study, the estimated synergism index was 1.11. Our results indicate that exposure to noise or a mixture of organic solvents may be associated with the prevalence of hypertension in car manufacturing company workers and co-exposure to noise and a mixture of solvents has an additive effect in this regard. Therefore appropriate preventive programs in these workers recommended. Copyright © 2012 Wiley Periodicals, Inc.

Phenolic Polymer Solvation in Water and Ethylene Glycol, I: Molecular Dynamics Simulations

NASA Technical Reports Server (NTRS)

Bucholz, Eric W.; Haskins, Justin B.; Monk, Joshua D.; Bauschlicher, Charles W.; Lawson, John W.

2017-01-01

Interactions between pre-cured phenolic polymer chains and a solvent have a significant impact on the structure and properties of the final post-cured phenolic resin. Developing an understanding of the nature of these interactions is important and will aid in the selection of the proper solvent that will lead to the desired final product. Here, we investigate the role of phenolic chain structure and solvent type on the overall solvation performance of the system through molecular dynamics simulations. Two types of solvents are considered, ethylene glycol (EGL) and H2O. In addition, three phenolic chain structures were considered including two novolac-type chains with either an ortho-ortho (OON) or ortho-para (OPN) backbone network and a resole-type (RES) chain with an ortho-ortho network. Each system is characterized through structural analysis of the solvation shell and hydrogen bonding environment as well as through quantification of the solvation free energy along with partitioned interaction energies between specific molecular species. The combination of the simulations and analyses indicate that EGL provides a larger solvation free energy than H2O due to more energetically favorable hydrophilic interactions as well as favorable hydrophobic interactions between CH element groups. In addition, phenolic chain structure significantly impacts solvation performance with OON having limited intermolecular hydrogen bond formations while OPN and RES interact more favorably with the solvent molecules. The results suggest that a resole-type phenolic chain with an ortho-para network should have the best solvation performance in EGL, H2O, and other similar solvents.

Phenolic Polymer Solvation in Water and Ethylene Glycol, I: Molecular Dynamics Simulations.

PubMed

Bucholz, Eric W; Haskins, Justin B; Monk, Joshua D; Bauschlicher, Charles W; Lawson, John W

2017-04-06

Interactions between pre-cured phenolic polymer chains and a solvent have a significant impact on the structure and properties of the final postcured phenolic resin. Developing an understanding of the nature of these interactions is important and will aid in the selection of the proper solvent that will lead to the desired final product. Here, we investigate the role of the phenolic chain structure and the solvent type on the overall solvation performance of the system through molecular dynamics simulations. Two types of solvents are considered: ethylene glycol (EGL) and H 2 O. In addition, three phenolic chain structures are considered, including two novolac-type chains with either an ortho-ortho (OON) or an ortho-para (OPN) backbone network and a resole-type (RES) chain with an ortho-ortho network. Each system is characterized through a structural analysis of the solvation shell and the hydrogen-bonding environment as well as through a quantification of the solvation free energy along with partitioned interaction energies between specific molecular species. The combination of simulations and the analyses indicate that EGL provides a higher solvation free energy than H 2 O due to more energetically favorable hydrophilic interactions as well as favorable hydrophobic interactions between CH element groups. In addition, the phenolic chain structure significantly affects the solvation performance, with OON having limited intermolecular hydrogen-bond formations, while OPN and RES interact more favorably with the solvent molecules. The results suggest that a resole-type phenolic chain with an ortho-para network should have the best solvation performance in EGL, H 2 O, and other similar solvents.

Interaction-component analysis of the hydration and urea effects on cytochrome c

NASA Astrophysics Data System (ADS)

Yamamori, Yu; Ishizuka, Ryosuke; Karino, Yasuhito; Sakuraba, Shun; Matubayasi, Nobuyuki

2016-02-01

Energetics was analyzed for cytochrome c in pure-water solvent and in a urea-water mixed solvent to elucidate the solvation effect in the structural variation of the protein. The solvation free energy was computed through all-atom molecular dynamics simulation combined with the solution theory in the energy representation, and its correlations were examined over sets of protein structures against the electrostatic and van der Waals components in the average interaction energy of the protein with the solvent and the excluded-volume component in the solvation free energy. It was observed in pure-water solvent that the solvation free energy varies in parallel to the electrostatic component with minor roles played by the van der Waals and excluded-volume components. The effect of urea on protein structure was then investigated in terms of the free-energy change upon transfer of the protein solute from pure-water solvent to the urea-water mixed solvent. The decomposition of the transfer free energy into the contributions from urea and water showed that the urea contribution is partially canceled by the water contribution and governs the total free energy of transfer. When correlated against the change in the solute-solvent interaction energy upon transfer and the corresponding changes in the electrostatic, van der Waals, and excluded-volume components, the transfer free energy exhibited strong correlations with the total change in the solute-solvent energy and its van der Waals component. The solute-solvent energy was decomposed into the contributions from the protein backbone and side chain, furthermore, and neither of the contributions was seen to be decisive in the correlation to the transfer free energy.

Auditory dysfunction associated with solvent exposure

PubMed Central

2013-01-01

Background A number of studies have demonstrated that solvents may induce auditory dysfunction. However, there is still little knowledge regarding the main signs and symptoms of solvent-induced hearing loss (SIHL). The aim of this research was to investigate the association between solvent exposure and adverse effects on peripheral and central auditory functioning with a comprehensive audiological test battery. Methods Seventy-two solvent-exposed workers and 72 non-exposed workers were selected to participate in the study. The test battery comprised pure-tone audiometry (PTA), transient evoked otoacoustic emissions (TEOAE), Random Gap Detection (RGD) and Hearing-in-Noise test (HINT). Results Solvent-exposed subjects presented with poorer mean test results than non-exposed subjects. A bivariate and multivariate linear regression model analysis was performed. One model for each auditory outcome (PTA, TEOAE, RGD and HINT) was independently constructed. For all of the models solvent exposure was significantly associated with the auditory outcome. Age also appeared significantly associated with some auditory outcomes. Conclusions This study provides further evidence of the possible adverse effect of solvents on the peripheral and central auditory functioning. A discussion of these effects and the utility of selected hearing tests to assess SIHL is addressed. PMID:23324255

Preferential melting of secondary structures during protein unfolding in different solvents: Competition between hydrophobic solvation and hydrogen bonding

NASA Astrophysics Data System (ADS)

Bagchi, Biman; Roy, Susmita; Ghosh, Rikhia

2014-03-01

Aqueous binary mixtures such as water-DMSO, water-urea, and water-ethanol are known to serve as denaturants of a host of proteins, although the detailed mechanism is often not known. Here we combine studies on several proteins in multiple binary mixtures to obtain a unified understanding of the phenomenon. We compare with experiments to support the simulation findings. The proteins considered include (i) chicken villin head piece (HP-36), (ii) immunoglobulin binding protein G (GB1), (iii) myoglobin and (iv) lysozyme. We find that for amphiphilic solvents like DMSO, the hydrophobic groups and the strong hydrogen bonding ability of the >S =O oxygen atom act together to facilitate the unfolding. However, the hydrophilic solvents like urea, due to the presence of more hydrophilic ends (C =O and two NH2) has a high propensity of forming hydrogen bonds with the side-chain residues and backbone of beta-sheet than the same of alpha helix. Such diversity among the unfolding pathways of a given protein in different chemical environments is especially characterized by the preferential solvation of a particular secondary structure.

Conformational studies of immunodominant myelin basic protein 1-11 analogues using NMR and molecular modeling

NASA Astrophysics Data System (ADS)

Laimou, Despina; Lazoura, Eliada; Troganis, Anastassios N.; Matsoukas, Minos-Timotheos; Deraos, Spyros N.; Katsara, Maria; Matsoukas, John; Apostolopoulos, Vasso; Tselios, Theodore V.

2011-11-01

Τwo dimensional nuclear magnetic resonance studies complimented by molecular dynamics simulations were conducted to investigate the conformation of the immunodominant epitope of acetylated myelin basic protein residues 1-11 (Ac-MBP1-11) and its altered peptide ligands, mutated at position 4 to an alanine (Ac-MBP1-11[4A]) or a tyrosine residue (Ac-MBP1-11[4Y]). Conformational analysis of the three analogues indicated that they adopt an extended conformation in DMSO solution as no long distance NOE connectivities were observed and seem to have a similar conformation when bound to the active site of the major histocompatibility complex (MHC II). The interaction of each peptide with MHC class II I-Au was further investigated in order to explore the molecular mechanism of experimental autoimmune encephalomyelitis induction/inhibition in mice. The present findings indicate that the Gln3 residue, which serves as a T-cell receptor (TCR) contact site in the TCR/peptide/I-Au complex, has a different orientation in the mutated analogues especially in the Ac-MBP1-11[4A] peptide. In particular the side chain of Gln3 is not solvent exposed as for the native Ac-MBP1-11 and it is not available for interaction with the TCR.

Subunit III-depleted cytochrome c oxidase provides insight into the process of proton uptake by proteins

PubMed Central

Varanasi, Lakshman; Hosler, Jonathan P.

2011-01-01

We review studies of subunit III-depleted cytochrome c oxidase (CcO III (−)) that elucidate the structural basis of steady-state proton uptake from solvent into an internal proton transfer pathway. The removal of subunit III from R. sphaeroides CcO makes proton uptake into the D pathway a rate-determining step, such that measurements of the pH dependence of steady-state O2 consumption can be used to compare the rate and functional pKa of proton uptake by D pathways containing different initial proton acceptors. The removal of subunit III also promotes spontaneous suicide inactivation by CcO, greatly shortening its catalytic lifespan. Because the probability of suicide inactivation is controlled by the rate at which the D pathway delivers protons to the active site, measurements of catalytic lifespan provide a second method to compare the relative efficacy of proton uptake by engineered CcO III (−) forms. These simple experimental systems have been used to explore general questions of proton uptake by proteins, such as the functional value of an initial proton acceptor, whether an initial acceptor must be surface-exposed, which side chains will function as initial proton acceptors and whether multiple acceptors can speed proton uptake. PMID:22023935

Thermal degradation of the solvent employed in the next-generation caustic-side solvent extraction process and its effect on the extraction, scrubbing, and stripping of cesium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roach, Benjamin D.; Williams, Neil J.; Moyer, Bruce A.

As part of the ongoing development of the Next-Generation Caustic-Side Solvent Extraction (NGS) process, the thermal stability of the process solvent was investigated and shown to be adequate for industrial application. The solvent was thermally treated at 35 C over a period of 13 months whilst in dynamic contact with each of the aqueous phases of the current NGS process, namely SRS 15 (a highly caustic waste simulant), sodium hydroxide scrub solution (0.025 M), and boric acid strip solution (0.01 M). The effect of thermal treatment was evaluated by assessing batch extract/scrub/strip performance as a function of time, by monitoringmore » the sodium extraction capacity of the solvent, and by analysis of the solvent using electrospray mass spectrometry. Current studies indicate that the NGS solvent should be thermally robust for a period of XXX months at the Modular Caustic-Side Solvent Extraction Unit (MCU) pilot plant located at Savannah River Site. Furthermore, the guanidine suppressor appears to be the solvent component most significantly impacted by thermal treatment of the solvent, showing significant degradation over time.« less

Thermal degradation of the solvent employed in the next-generation caustic-side solvent extraction process and its effect on the extraction, scrubbing, and stripping of cesium

DOE PAGES

Roach, Benjamin D.; Williams, Neil J.; Moyer, Bruce A.

2015-09-02

As part of the ongoing development of the Next-Generation Caustic-Side Solvent Extraction (NGS) process, the thermal stability of the process solvent was investigated and shown to be adequate for industrial application. The solvent was thermally treated at 35 C over a period of 13 months whilst in dynamic contact with each of the aqueous phases of the current NGS process, namely SRS 15 (a highly caustic waste simulant), sodium hydroxide scrub solution (0.025 M), and boric acid strip solution (0.01 M). The effect of thermal treatment was evaluated by assessing batch extract/scrub/strip performance as a function of time, by monitoringmore » the sodium extraction capacity of the solvent, and by analysis of the solvent using electrospray mass spectrometry. Current studies indicate that the NGS solvent should be thermally robust for a period of XXX months at the Modular Caustic-Side Solvent Extraction Unit (MCU) pilot plant located at Savannah River Site. Furthermore, the guanidine suppressor appears to be the solvent component most significantly impacted by thermal treatment of the solvent, showing significant degradation over time.« less

Enhanced photophysics of conjugated polymers

DOEpatents

Chen, Liaohai [Argonne, IL; Xu, Su [Santa Clara, CA; McBranch, Duncan [Santa Fe, NM; Whitten, David [Santa Fe, NM

2003-05-27

The addition of oppositely charged surfactant to fluorescent ionic conjugated polymer forms a polymer-surfactant complex that exhibits at least one improved photophysical property. The conjugated polymer is a fluorescent ionic polymer that typically has at least one ionic side chain or moiety that interacts with the specific surfactant selected. The photophysical property improvements may include increased fluorescence quantum efficiency, wavelength-independent emission and absorption spectra, and more stable fluorescence decay kinetics. The complexation typically occurs in a solution of a polar solvent in which the polymer and surfactant are soluble, but it may also occur in a mixture of solvents. The solution is commonly prepared with a surfactant molecule:monomer repeat unit of polymer ratio ranging from about 1:100 to about 1:1. A polymer-surfactant complex precipitate is formed as the ratio approaches 1:1. This precipitate is recoverable and usable in many forms.

Polymer Film Dewetting by Water/Surfactant/Good-Solvent Mixtures: A Mechanistic Insight and Its Implications for the Conservation of Cultural Heritage.

PubMed

Baglioni, Michele; Montis, Costanza; Chelazzi, David; Giorgi, Rodorico; Berti, Debora; Baglioni, Piero

2018-06-18

Aqueous nanostructured fluids (NSFs) have been proposed to remove polymer coatings from the surface of works of art; this process usually involves film dewetting. The NSF cleaning mechanism was studied using several techniques that were employed to obtain mechanistic insight on the interaction of a methacrylic/acrylic copolymer (Paraloid B72) film laid on glass surfaces and several NSFs, based on two solvents and two surfactants. The experimental results provide a detailed picture of the dewetting process. The gyration radius and the reduction of the T g of Paraloid B72 fully swollen in the two solvents is larger for propylene carbonate than for methyl ethyl ketone, suggesting higher mobility of polymer chains for the former, while a nonionic alcohol ethoxylate surfactant was more effective than sodium dodecylsulfate in favoring the dewetting process. FTIR 2D imaging showed that the dewetting patterns observed on model samples are also present on polymer-coated mortar tiles when exposed to NSFs. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

ω-Turn: a novel β-turn mimic in globular proteins stabilized by main-chain to side-chain C−H···O interaction.

PubMed

Dhar, Jesmita; Chakrabarti, Pinak; Saini, Harpreet; Raghava, Gajendra Pal Singh; Kishore, Raghuvansh

2015-02-01

Mimicry of structural motifs is a common feature in proteins. The 10-membered hydrogen-bonded ring involving the main-chain C − O in a β-turn can be formed using a side-chain carbonyl group leading to Asx-turn. We show that the N − H component of hydrogen bond can be replaced by a C(γ) -H group in the side chain, culminating in a nonconventional C − H···O interaction. Because of its shape this β-turn mimic is designated as ω-turn, which is found to occur ∼ three times per 100 residues. Three residues (i to i + 2) constitute the turn with the C − H···O interaction occurring between the terminal residues, constraining the torsion angles ϕi + 1, ψi + 1, ϕi + 2 and χ'1(i + 2) (using the interacting C(γ) atom). Based on these angles there are two types of ω-turns, each of which can be further divided into two groups. C(β) -branched side-chains, and Met and Gln have high propensities to occur at i + 2; for the last two residues the carbonyl oxygen may participate in an additional interaction involving the S and amino group, respectively. With Cys occupying the i + 1 position, such turns are found in the metal-binding sites. N-linked glycosylation occurs at the consensus pattern Asn-Xaa-Ser/Thr; with Thr at i + 2, the sequence can adopt the secondary structure of a ω-turn, which may be the recognition site for protein modification. Location between two β-strands is the most common occurrence in protein tertiary structure, and being generally exposed ω-turn may constitute the antigenic determinant site. It is a stable scaffold and may be used in protein engineering and peptide design. © 2014 Wiley Periodicals, Inc.

Structure-based analysis reveals hydration changes induced by arginine hydrochloride.

PubMed

Nakakido, Makoto; Tanaka, Yoshikazu; Mitsuhori, Mariko; Kudou, Motonori; Ejima, Daisuke; Arakawa, Tsutomu; Tsumoto, Kouhei

2008-10-01

Arginine hydrochloride has been used to suppress protein aggregation during refolding and in various other applications. We investigated the structure of hen egg-white lysozyme (HEL) and solvent molecules in arginine hydrochloride solution by X-ray crystallography. Neither the backbone nor side-chain structure of HEL was altered by the presence of arginine hydrochloride. In addition, no stably bound arginine molecules were observed. The number of hydration water molecules, however, changed with the arginine hydrochloride concentration. We suggest that arginine hydrochloride suppresses protein aggregation by altering the hydration structure and the transient binding of arginine molecules that could not be observed.

An Experimental and Computational Investigation into the Gas-Phase Acidities of Tyrosine and Phenylalanine: Three Structures for Deprotonated Tyrosine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bokatzian, Samantha S.; Stover, Michele L.; Plummer, Chelsea E.

Using mass spectrometry and correlated molecular orbital theory, three deprotonated structures were revealed for the amino acid tyrosine. The structures were distinguished experimentally by ion/molecule reactions involving proton transfer and trimethylsilyl azide. Gas-phase acidities from proton transfer reactions and from G3(MP2) calculations generally agree well. The lowest energy structure, which was only observed experimentally using electrospray ionization from aprotic solvents, is deprotonated at the carboxylic acid group and is predicted to be highly folded. A second unfolded carboxylate structure is several kcal/mol higher in energy and primarily forms from protic solvents. Protic solvents also yield a structure deprotonated at themore » phenolic side chain, which experiments find to be intermediate in energy to the two carboxylate forms. G3(MP2) calculations indicate that the three structures differ in energy by only 2.5 kcal/mol, yet they are readily distinguished experimentally. Structural abundance ratios are dependent upon experimental conditions, including the solvent and accumulation time of ions in a hexapole. Under some conditions, carboxylate ions may convert to phenolate ions. For phenylalanine, which lacks a phenolic group, only one deprotonated structure was observed experimentally when electrosprayed from protic solvent. This agrees with G3(MP2) calculations that find the folded and unfolded carboxylate forms to differ by 0.3 kcal/mol.« less

Self-interacting polymer chains terminally anchored to adsorbing surfaces of three-dimensional fractal lattices

NASA Astrophysics Data System (ADS)

Živić, I.; Elezović-Hadžić, S.; Milošević, S.

2018-01-01

We have studied the adsorption problem of self-attracting linear polymers, modeled by self-avoiding walks (SAWs), situated on three-dimensional fractal structures, exemplified by 3d Sierpinski gasket (SG) family of fractals as containers of a poor solvent. Members of SG family are enumerated by an integer b (b ≥ 2), and it is assumed that one side of each SG fractal is an impenetrable adsorbing surface. We calculate the critical exponents γ1 ,γ11, and γs, which are related to the numbers of all possible SAWs with one, both, and no ends anchored to the adsorbing boundary, respectively. By applying the exact renormalization group (RG) method (for the first three members of the SG fractal family, b = 2 , 3, and 4), we have obtained specific values of these exponents, for θ-chain and globular polymer phase. We discuss their mutual relations and relations with corresponding values pertinent to extended polymer chain phase.

Toward the accurate first-principles prediction of ionization equilibria in proteins.

PubMed

Khandogin, Jana; Brooks, Charles L

2006-08-08

The calculation of pK(a) values for ionizable sites in proteins has been traditionally based on numerical solutions of the Poisson-Boltzmann equation carried out using a high-resolution protein structure. In this paper, we present a method based on continuous constant pH molecular dynamics (CPHMD) simulations, which allows the first-principles description of protein ionization equilibria. Our method utilizes an improved generalized Born implicit solvent model with an approximate Debye-Hückel screening function to account for salt effects and the replica-exchange (REX) protocol for enhanced conformational and protonation state sampling. The accuracy and robustness of the present method are demonstrated by 1 ns REX-CPHMD titration simulations of 10 proteins, which exhibit anomalously large pK(a) shifts for the carboxylate and histidine side chains. The experimental pK(a) values of these proteins are reliably reproduced with a root-mean-square error ranging from 0.6 unit for proteins containing few buried ionizable side chains to 1.0 unit or slightly higher for proteins containing ionizable side chains deeply buried in the core and experiencing strong charge-charge interactions. This unprecedented level of agreement with experimental benchmarks for the de novo calculation of pK(a) values suggests that the CPHMD method is maturing into a practical tool for the quantitative prediction of protein ionization equilibria, and this, in turn, opens a door to atomistic simulations of a wide variety of pH-coupled conformational phenomena in biological macromolecules such as protein folding or misfolding, aggregation, ligand binding, membrane interaction, and catalysis.

Conjugated Polymers Atypically Prepared in Water

PubMed Central

Invernale, Michael A.; Pendergraph, Samuel A.; Yavuz, Mustafa S.; Ombaba, Matthew; Sotzing, Gregory A.

2010-01-01

Processability remains a fundamental issue for the implementation of conducting polymer technology. A simple synthetic route towards processable precursors to conducting polymers (main chain and side chain) was developed using commercially available materials. These soluble precursor systems were converted to conjugated polymers electrochemically in aqueous media, offering a cheaper and greener method of processing. Oxidative conversion in aqueous and organic media each produced equivalent electrochromics. The precursor method enhances the yield of the electrochromic polymer obtained over that of electrodeposition, and it relies on a less corruptible electrolyte bath. However, electrochemical conversion of the precursor polymers often relies on organic salts and solvents. The ability to achieve oxidative conversion in brine offers a less costly and a more environmentally friendly processing step. It is also beneficial for biological applications. The electrochromics obtained herein were evaluated for electronic, spectral, and morphological properties. PMID:20959869

Nucleation Process of a Fibril Precursor in the C-Terminal Segment of Amyloid-β

NASA Astrophysics Data System (ADS)

Baftizadeh, Fahimeh; Pietrucci, Fabio; Biarnés, Xevi; Laio, Alessandro

2013-04-01

By extended atomistic simulations in explicit solvent and bias-exchange metadynamics, we study the aggregation process of 18 chains of the C-terminal segment of amyloid-β, an intrinsically disordered protein involved in Alzheimer’s disease and prone to form fibrils. Starting from a disordered aggregate, we are able to observe the formation of an ordered nucleus rich in beta sheets. The rate limiting step in the nucleation pathway involves crossing a barrier of approximately 40kcal/mol and is associated with the formation of a very specific interdigitation of the side chains belonging to different sheets. This structural pattern is different from the one observed experimentally in a microcrystal of the same system, indicating that the structure of a “nascent” fibril may differ from the one of an “extended” fibril.

Design of polymer conjugated 3-helix micelles as nanocarriers with tunable shapes.

PubMed

Ma, Dan; DeBenedictis, Elizabeth P; Lund, Reidar; Keten, Sinan

2016-11-24

Amphiphilic peptide-polymer conjugates have the ability to form stable nanoscale micelles, which show great promise for drug delivery and other applications. A recent design has utilized the end-conjugation of alkyl chains to 3-helix coiled coils to achieve amphiphilicity, combined with the side-chain conjugation of polyethylene glycol (PEG) to tune micelle size through entropic confinement forces. Here we investigate this phenomenon in depth, using coarse-grained dissipative particle dynamics (DPD) simulations in an explicit solvent and micelle theory. We analyze the conformations of PEG chains conjugated to three different positions on 3-helix bundle peptides to ascertain the degree of confinement upon assembly, as well as the ordering of the subunits making up the micelle. We discover that the micelle size and stability is dictated by a competition between the entropy of PEG chain conformations in the assembled state, as well as intermolecular cross-interactions among PEG chains that promote cohesion between neighboring conjugates. Our analyses build on the role of PEG molecular weight and conjugation site and lead to computational phase diagrams that can be used to design 3-helix micelles. This work opens pathways for the design of multifunctional micelles with tunable size, shape and stability.

Structure of rigid polymers confined to nanoparticles: Molecular dynamics simulations insight

DOE PAGES

Maskey, Sabina; Lane, J. Matthew D.; Perahia, Dvora; ...

2016-02-04

Nanoparticles (NPs) grafted with organic layers form hybrids able to retain their unique properties through integration into the mesoscopic scale. The organic layer structure and response often determine the functionality of the hybrids on the mesoscopic length scale. Using molecular dynamics (MD) simulations, we probe the conformation of luminescent rigid polymers, dialkyl poly(p-phenylene ethynylene)s (PPE), end-grafted onto a silica nanoparticle in different solvents as the molecular weights and polymer coverages are varied. We find that, in contrast to NP-grafted flexible polymers, the chains are fully extended independent of the solvent. In toluene and decane, which are good solvents, the graftedmore » PPEs chains assume a similar conformation to that observed in dilute solutions. In water, which is a poor solvent for the PPEs, the polymer chains form one large cluster but remain extended. The radial distribution of the chains around the core of the nanoparticle is homogeneous in good solvents, whereas in poor solvents clusters are formed independent of molecular weights and coverages. As a result, the clustering is distinctively different from the response of grafted flexible and semiflexible polymers.« less

Critical Casimir effect in a polymer chain in supercritical solvents.

PubMed

Sumi, Tomonari; Imazaki, Nobuyuki; Sekino, Hideo

2009-03-01

Density fluctuation effects on the conformation of a polymer chain in a supercritical solvent were investigated by performing a multiscale simulation based on the density-functional theory. We found (a) a universal swelling of the polymer chain near the critical point, irrespective of whether the polymer chain is solvophilic or solvophobic, and (b) a characteristic collapse of the polymer chain having a strong solvophilicity at a temperature slightly higher than the critical point, where the isothermal compressibility becomes less than the ideal one.

System for removing contaminants from plastic resin

DOEpatents

Bohnert, George W.; Hand, Thomas E.; DeLaurentiis, Gary M.

2010-11-23

A resin recycling system that produces essentially contaminant-free synthetic resin material in an environmentally safe and economical manner. The system includes receiving the resin in container form. A grinder grinds the containers into resin particles. The particles are exposed to a solvent in one or more solvent wash vessels, the solvent contacting the resin particles and substantially removing contaminants on the resin particles. A separator is used to separate the resin particles and the solvent. The resin particles are then placed in solvent removing element where they are exposed to a solvent removing agent which removes any residual solvent remaining on the resin particles after separation.

The solvent effects on dimethyl phthalate investigated by FTIR characterization, solvent parameter correlation and DFT computation

NASA Astrophysics Data System (ADS)

Chen, Yi; Zhang, Hui; Zhou, Wenzhao; Deng, Chao; Liao, Jian

2018-06-01

This study set out with the aim of investigating the solvent effects on dimethyl phthalate (DMP) using FTIR characterization, solvent parameter correlation and DFT calculation. DMP exposed to 17 organic solvents manifested varying shift in the carbonyl stretching vibration frequency (νCdbnd O). Non-alkanols induced Band I and alkanols produced Band I and Band II. Through correlating the νCdbnd O with the empirical solvent scales including acceptor parameter (AN), Schleyer's linear free energy parameter (G), and linear free salvation energy relationships (LSER), Band I was mainly ascribed to non-specific effects from either non-alkanols or alkanol polymers ((alkanol)n). νCdbnd O of the latter indicated minor red shift and less variability compared to the former. An assumption was made and validated about the sequestering of hydroxyl group by the bulky hydrophobic chain in (alkanol)n, creating what we refer to as "screening effects". Ab initio calculation, on the other hand, provided insights for possible hydrogen binding between DMP and (ethanol)n or between ethanol monomers. The two components of Band I observed in inert solvents were assigned to the two Cdbnd O groups adopting differentiated conformations. This in turn prompted our consideration that hydrogen binding was highly selective in favor of lowly associated (alkanol)n and the particular Cdbnd O group having relatively less steric hindrance and stronger electron-donating capacity. Band II was therefore believed to derive from hydrogen-bond interactions mainly in manner of 1:1 and 1:2 DMP-(alkanol)n complexes.

Method of performing sugar dehydration and catalyst treatment

DOEpatents

Hu, Jianli [Kennewick, WA; Holladay, Johnathan E [Kennewick, WA; Zhang, Xinjie [Burlington, MA; Wang, Yong [Richland, WA

2010-06-01

The invention includes a method of treating a solid acid catalyst. After exposing the catalyst to a mixture containing a sugar alcohol, the catalyst is washed with an organic solvent and is then exposed to a second reaction mixture. The invention includes a process for production of anhydrosugar alcohol. A solid acid catalyst is provided to convert sugar alcohol in a first sample to an anhydrosugar alcohol. The catalyst is then washed with an organic solvent and is subsequently utilized to expose a second sample. The invention includes a method for selective production of an anhydrosugar. A solid acid catalyst is provided within a reactor and anhydrosugar alcohol is formed by flowing a starting sugar alcohol into the reactor. The acid catalyst is then exposed to an organic solvent which allows a greater amount of additional anhydrosugar to be produced than would occur without exposing the acid catalyst to the organic solvent.

Effects of low urea concentrations on protein-water interactions.

PubMed

Ferreira, Luisa A; Povarova, Olga I; Stepanenko, Olga V; Sulatskaya, Anna I; Madeira, Pedro P; Kuznetsova, Irina M; Turoverov, Konstantin K; Uversky, Vladimir N; Zaslavsky, Boris Y

2017-01-01

Solvent properties of aqueous media (dipolarity/polarizability, hydrogen bond donor acidity, and hydrogen bond acceptor basicity) were measured in the coexisting phases of Dextran-PEG aqueous two-phase systems (ATPSs) containing .5 and 2.0 M urea. The differences between the electrostatic and hydrophobic properties of the phases in the ATPSs were quantified by analysis of partitioning of the homologous series of sodium salts of dinitrophenylated amino acids with aliphatic alkyl side chains. Furthermore, partitioning of eleven different proteins in the ATPSs was studied. The analysis of protein partition behavior in a set of ATPSs with protective osmolytes (sorbitol, sucrose, trehalose, and TMAO) at the concentration of .5 M, in osmolyte-free ATPS, and in ATPSs with .5 or 2.0 M urea in terms of the solvent properties of the phases was performed. The results show unambiguously that even at the urea concentration of .5 M, this denaturant affects partitioning of all proteins (except concanavalin A) through direct urea-protein interactions and via its effect on the solvent properties of the media. The direct urea-protein interactions seem to prevail over the urea effects on the solvent properties of water at the concentration of .5 M urea and appear to be completely dominant at 2.0 M urea concentration.

Auditory Effects of Exposure to Noise and Solvents: A Comparative Study

PubMed Central

Lobato, Diolen Conceição Barros; Lacerda, Adriana Bender Moreira De; Gonçalves, Cláudia Giglio De Oliveira; Coifman, Herton

2013-01-01

Introduction Industry workers are exposed to different environmental risk agents that, when combined, may potentiate risks to hearing. Objective To evaluate the effects of the combined exposure to noise and solvents on hearing in workers. Methods A transversal retrospective cohort study was performed through documentary analysis of an industry. The sample (n = 198) was divided into four groups: the noise group (NG), exposed only to noise; the noise and solvents group (NSG), exposed to noise and solvents; the noise control group and noise and solvents control group (CNS), no exposure. Results The NG showed 16.66% of cases suggestive of bilateral noise-induced hearing loss and NSG showed 5.26%. The NG and NSG had worse thresholds than their respective control groups. Females were less susceptible to noise than males; however, when simultaneously exposed to solvents, hearing was affected in a similar way, resulting in significant differences (p < 0.05). The 40- to 49-year-old age group was significantly worse (p < 0.05) in the auditory thresholds in the NSG compared with the CNS. Conclusion The results observed in this study indicate that simultaneous exposure to noise and solvents can damage the peripheral auditory system. PMID:25992079

Protein structure modeling and refinement by global optimization in CASP12.

PubMed

Hong, Seung Hwan; Joung, InSuk; Flores-Canales, Jose C; Manavalan, Balachandran; Cheng, Qianyi; Heo, Seungryong; Kim, Jong Yun; Lee, Sun Young; Nam, Mikyung; Joo, Keehyoung; Lee, In-Ho; Lee, Sung Jong; Lee, Jooyoung

2018-03-01

For protein structure modeling in the CASP12 experiment, we have developed a new protocol based on our previous CASP11 approach. The global optimization method of conformational space annealing (CSA) was applied to 3 stages of modeling: multiple sequence-structure alignment, three-dimensional (3D) chain building, and side-chain re-modeling. For better template selection and model selection, we updated our model quality assessment (QA) method with the newly developed SVMQA (support vector machine for quality assessment). For 3D chain building, we updated our energy function by including restraints generated from predicted residue-residue contacts. New energy terms for the predicted secondary structure and predicted solvent accessible surface area were also introduced. For difficult targets, we proposed a new method, LEEab, where the template term played a less significant role than it did in LEE, complemented by increased contributions from other terms such as the predicted contact term. For TBM (template-based modeling) targets, LEE performed better than LEEab, but for FM targets, LEEab was better. For model refinement, we modified our CASP11 molecular dynamics (MD) based protocol by using explicit solvents and tuning down restraint weights. Refinement results from MD simulations that used a new augmented statistical energy term in the force field were quite promising. Finally, when using inaccurate information (such as the predicted contacts), it was important to use the Lorentzian function for which the maximal penalty arising from wrong information is always bounded. © 2017 Wiley Periodicals, Inc.

Interaction Enthalpy of Side Chain and Backbone Amides in Polyglutamine Solution Monomers and Fibrils.

PubMed

Punihaole, David; Jakubek, Ryan S; Workman, Riley J; Asher, Sanford A

2018-04-19

We determined an empirical correlation that relates the amide I vibrational band frequencies of the glutamine (Q) side chain to the strength of hydrogen bonding, van der Waals, and Lewis acid-base interactions of its primary amide carbonyl. We used this correlation to determine the Q side chain carbonyl interaction enthalpy (Δ H int ) in monomeric and amyloid-like fibril conformations of D 2 Q 10 K 2 (Q10). We independently verified these Δ H int values through molecular dynamics simulations that showed excellent agreement with experiments. We found that side chain-side chain and side chain-peptide backbone interactions in fibrils and monomers are more enthalpically favorable than are Q side chain-water interactions. Q10 fibrils also showed a more favorable Δ H int for side chain-side chain interactions compared to backbone-backbone interactions. This work experimentally demonstrates that interamide side chain interactions are important in the formation and stabilization of polyQ fibrils.

From Comb-like Polymers to Bottle-Brushes

NASA Astrophysics Data System (ADS)

Liang, Heyi; Cao, Zhen; Dobrynin, Andrey; Sheiko, Sergei

We use a combination of the coarse-grained molecular dynamics simulations and scaling analysis to study conformations of bottle-brushes and comb-like polymers in a melt. Our analysis show that bottle-brushes and comb-like polymers can be in four different conformation regimes depending on the number of monomers between grafted side chains and side chain degree of polymerization. In loosely-grafted comb regime (LC) the degree of polymerization between side chains is longer than side chain degree of polymerization, such that the side chains belonging to the same macromolecule do not overlap. Crossover to a new densely-grafted comb regime (DC) takes place when side chains begin to overlap reducing interpenetration of side chains belonging to different macromolecules. In these two regimes both side-chains and backbone behave as unperturbed linear chains with the effective Kuhn length of the backbone being close to that of linear chain. Further decrease spacer degree of polymerization results in crossover to loosely-grafted bottle-brush regime (LB). In this regime, the bottle-brush backbone is stretched while the side-chains still maintain ideal chain conformation. Finally, for even shorter spacer between grafted side chains, which corresponds to densely-grafted bottle-brush regime (DB), the backbone adopts a fully extended chain conformation, and side-chains begin to stretch to maintain a constant monomer density. NSF DMR-1409710, DMR-1407645, DMR-1624569, DMR-1436201.

Formation of silk fibroin nanoparticles in water-miscible organic solvent and their characterization

NASA Astrophysics Data System (ADS)

Zhang, Yu-Qing; Shen, Wei-De; Xiang, Ru-Li; Zhuge, Lan-Jian; Gao, Wei-Jian; Wang, Wen-Bao

2007-10-01

When Silk fibre derived from Bombyx mori, a native biopolymer, was dissolved in highly concentrated neutral salts such as CaCl2, the regenerated liquid silk, a gradually degraded peptide mixture of silk fibroin, could be obtained. The silk fibroin nanoparticles were prepared rapidly from the liquid silk by using water-miscible protonic and polar aprotonic organic solvents. The nanoparticles are insoluble but well dispersed and stable in aqueous solution and are globular particles with a range of 35-125 nm in diameter by means of TEM, SEM, AFM and laser sizer. Over one half of the ɛ-amino groups exist around the protein nanoparticles by using a trinitrobenzenesulfonic acid (TNBS) method. Raman spectra shows the tyrosine residues on the surface of the globules are more exposed than those on native silk fibers. The crystalline polymorph and conformation transition of the silk nanoparticles from random-coil and α-helix form (Silk I) into anti-parallel β-sheet form (Silk II) are investigated in detail by using infrared, fluorescence and Raman spectroscopy, DSC, 13C CP-MAS NMR and electron diffraction. X-ray diffraction of the silk nanoparticles shows that the nanoparticles crystallinity is about four fifths of the native fiber. Our results indicate that the degraded peptide chains of the regenerated silk is gathered homogeneously or heterogeneously to form a looser globular structure in aqueous solution. When introduced into excessive organic solvent, the looser globules of the liquid silk are rapidly dispersed and simultaneously dehydrated internally and externally, resulting in the further chain-chain contact, arrangement of those hydrophobic domains inside the globules and final formation of crystalline silk nanoparticles with β-sheet configuration. The morphology and size of the nanoparticles are relative to the kinds, properties and even molecular structures of organic solvents, and more significantly to the looser globular substructure of the degraded silk fibroin in aqueous solution. It is possible that the silk protein nanoparticles are potentially useful in biomaterials such as cosmetics, anti-UV skincare products, industrial materials and surface improving materials, especially in enzyme/drug delivery system as vehicle.

Long Dynamics Simulations of Proteins Using Atomistic Force Fields and a Continuum Representation of Solvent Effects: Calculation of Structural and Dynamic Properties

PubMed Central

Li, Xianfeng; Hassan, Sergio A.; Mehler, Ernest L.

2006-01-01

Long dynamics simulations were carried out on the B1 immunoglobulin-binding domain of streptococcal protein G (ProtG) and bovine pancreatic trypsin inhibitor (BPTI) using atomistic descriptions of the proteins and a continuum representation of solvent effects. To mimic frictional and random collision effects, Langevin dynamics (LD) were used. The main goal of the calculations was to explore the stability of tens-of-nanosecond trajectories as generated by this molecular mechanics approximation and to analyze in detail structural and dynamical properties. Conformational fluctuations, order parameters, cross correlation matrices, residue solvent accessibilities, pKa values of titratable groups, and hydrogen-bonding (HB) patterns were calculated from all of the trajectories and compared with available experimental data. The simulations comprised over 40 ns per trajectory for ProtG and over 30 ns per trajectory for BPTI. For comparison, explicit water molecular dynamics simulations (EW/MD) of 3 ns and 4 ns, respectively, were also carried out. Two continuum simulations were performed on each protein using the CHARMM program, one with the all-atom PAR22 representation of the protein force field (here referred to as PAR22/LD simulations) and the other with the modifications introduced by the recently developed CMAP potential (CMAP/LD simulations). The explicit solvent simulations were performed with PAR22 only. Solvent effects are described by a continuum model based on screened Coulomb potentials (SCP) reported earlier, i.e., the SCP-based implicit solvent model (SCP–ISM). For ProtG, both the PAR22/LD and the CMAP/LD 40-ns trajectories were stable, yielding Cα root mean square deviations (RMSD) of about 1.0 and 0.8 Å respectively along the entire simulation time, compared to 0.8 Å for the EW/MD simulation. For BPTI, only the CMAP/LD trajectory was stable for the entire 30-ns simulation, with a Cα RMSD of ≈ 1.4 Å, while the PAR22/LD trajectory became unstable early in the simulation, reaching a Cα RMSD of about 2.7 Å and remaining at this value until the end of the simulation; the Cα RMSD of the EW/MD simulation was about 1.5 Å. The source of the instabilities of the BPTI trajectories in the PAR22/LD simulations was explored by an analysis of the backbone torsion angles. To further validate the findings from this analysis of BPTI, a 35-ns SCP–ISM simulation of Ubiquitin (Ubq) was carried out. For this protein, the CMAP/LD simulation was stable for the entire simulation time (Cα RMSD of ≈1.0 Å), while the PAR22/LD trajectory showed a trend similar to that in BPTI, reaching a Cα RMSD of ≈1.5 Å at 7 ns. All the calculated properties were found to be in agreement with the corresponding experimental values, although local deviations were also observed. HB patterns were also well reproduced by all the continuum solvent simulations with the exception of solvent-exposed side chain–side chain (sc–sc) HB in ProtG, where several of the HB interactions observed in the crystal structure and in the EW/MD simulation were lost. The overall analysis reported in this work suggests that the combination of an atomistic representation of a protein with a CMAP/CHARMM force field and a continuum representation of solvent effects such as the SCP–ISM provides a good description of structural and dynamic properties obtained from long computer simulations. Although the SCP–ISM simulations (CMAP/LD) reported here were shown to be stable and the properties well reproduced, further refinement is needed to attain a level of accuracy suitable for more challenging biological applications, particularly the study of protein–protein interactions. PMID:15959866

The local phase transitions of the solvent in the neighborhood of a solvophobic polymer at high pressures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budkov, Yu. A., E-mail: urabudkov@rambler.ru; National Research University Higher School of Economics, Moscow; Department of Chemistry, Lomonosov Moscow State University, Moscow

2014-11-28

We investigate local phase transitions of the solvent in the neighborhood of a solvophobic polymer chain which is induced by a change of the polymer-solvent repulsion and the solvent pressure in the bulk solution. We describe the polymer in solution by the Edwards model, where the conditional partition function of the polymer chain at a fixed radius of gyration is described by a mean-field theory. The contributions of the polymer-solvent and the solvent-solvent interactions to the total free energy are described within the mean-field approximation. We obtain the total free energy of the solution as a function of the radiusmore » of gyration and the average solvent number density within the gyration volume. The resulting system of coupled equations is solved varying the polymer-solvent repulsion strength at high solvent pressure in the bulk. We show that the coil-globule (globule-coil) transition occurs accompanied by a local solvent evaporation (condensation) within the gyration volume.« less

Insights into the phosphoregulation of beta-secretase sorting signal by the VHS domain of GGA1.

PubMed

Shiba, Tomoo; Kametaka, Satoshi; Kawasaki, Masato; Shibata, Masahiro; Waguri, Satoshi; Uchiyama, Yasuo; Wakatsuki, Soichi

2004-06-01

BACE (beta-site amyloid precursor protein cleaving enzyme, beta-secretase) is a type-I membrane protein which functions as an aspartic protease in the production of beta-amyloid peptide, a causative agent of Alzheimer's disease. Its cytoplasmic tail has a characteristic acidic-cluster dileucine motif recognized by the VHS domain of adaptor proteins, GGAs (Golgi-localizing, gamma-adaptin ear homology domain, ARF-interacting). Here we show that BACE is colocalized with GGAs in the trans-Golgi network and peripheral structures, and phosphorylation of a serine residue in the cytoplasmic tail enhances interaction with the VHS domain of GGA1 by about threefold. The X-ray crystal structure of the complex between the GGA1-VHS domain and the BACE C-terminal peptide illustrates a similar recognition mechanism as mannose 6-phosphate receptors except that a glutamine residue closes in to fill the gap created by the shorter BACE peptide. The serine and lysine of the BACE peptide point their side chains towards the solvent. However, phosphorylation of the serine affects the lysine side chain and the peptide backbone, resulting in one additional hydrogen bond and a stronger electrostatic interaction with the VHS domain, hence the reversible increase in affinity.

Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations

PubMed Central

Baxa, Michael C.; Haddadian, Esmael J.; Jumper, John M.; Freed, Karl F.; Sosnick, Tobin R.

2014-01-01

The loss of conformational entropy is a major contribution in the thermodynamics of protein folding. However, accurate determination of the quantity has proven challenging. We calculate this loss using molecular dynamic simulations of both the native protein and a realistic denatured state ensemble. For ubiquitin, the total change in entropy is TΔSTotal = 1.4 kcal⋅mol−1 per residue at 300 K with only 20% from the loss of side-chain entropy. Our analysis exhibits mixed agreement with prior studies because of the use of more accurate ensembles and contributions from correlated motions. Buried side chains lose only a factor of 1.4 in the number of conformations available per rotamer upon folding (ΩU/ΩN). The entropy loss for helical and sheet residues differs due to the smaller motions of helical residues (TΔShelix−sheet = 0.5 kcal⋅mol−1), a property not fully reflected in the amide N-H and carbonyl C=O bond NMR order parameters. The results have implications for the thermodynamics of folding and binding, including estimates of solvent ordering and microscopic entropies obtained from NMR. PMID:25313044

The universality of β-hairpin misfolding indicated by molecular dynamics simulations.

PubMed

Shao, Qiang; Wang, Jinan; Shi, Jiye; Zhu, Weiliang

2013-10-28

Previous molecular dynamics simulations showed that besides the experimentally measured folded structures, several β-structured polypeptides could also have misfolded "out-of-register" structures. Through the enhanced sampling molecular dynamics simulations on a series of polypeptides using either implicit or explicit solvent model, the present study systematically investigated the universality of β-hairpin misfolding and its determinants. It was observed that the misfolding could take place for almost all polypeptides under study, especially in the presence of weak side chain hydrophobicity. Moreover, the observed misfolded structures for various polypeptides share the following common features: (1) the turn length in misfolded structure is one-residue shorter than that in folded structure; (2) the hydrophobic side chains on the two strands are pointed to the opposite directions instead of packing in the same direction to form hydrophobic core cluster in the folded structure; and (3) the misfolded structure is one-residue-shifted asymmetric β-hairpin structure. The detailed analysis suggested that the misfolding of β-hairpin is the result of the competition between the formation of the alterable turn configurations and the inter-strand hydrophobic interactions. These predictions are desired to be tested by experiments.

The universality of β-hairpin misfolding indicated by molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Shao, Qiang; Wang, Jinan; Shi, Jiye; Zhu, Weiliang

2013-10-01

Previous molecular dynamics simulations showed that besides the experimentally measured folded structures, several β-structured polypeptides could also have misfolded "out-of-register" structures. Through the enhanced sampling molecular dynamics simulations on a series of polypeptides using either implicit or explicit solvent model, the present study systematically investigated the universality of β-hairpin misfolding and its determinants. It was observed that the misfolding could take place for almost all polypeptides under study, especially in the presence of weak side chain hydrophobicity. Moreover, the observed misfolded structures for various polypeptides share the following common features: (1) the turn length in misfolded structure is one-residue shorter than that in folded structure; (2) the hydrophobic side chains on the two strands are pointed to the opposite directions instead of packing in the same direction to form hydrophobic core cluster in the folded structure; and (3) the misfolded structure is one-residue-shifted asymmetric β-hairpin structure. The detailed analysis suggested that the misfolding of β-hairpin is the result of the competition between the formation of the alterable turn configurations and the inter-strand hydrophobic interactions. These predictions are desired to be tested by experiments.

Sulfamide-Lattice Restructuring To Form Dimensionally Controlled Molecular Arrays and Gel-Forming Systems.

PubMed

Raghava, Saripalli V; Gopinath, Pushparathinam; Srivastava, Bhartendu K; Ramkumar, Venkatachalam; Muraleedharan, Kannoth M

2017-03-13

A design approach that incorporates structural requirements for the formation of a 1D assembly, fibril stability, and fibril-fibril interactions for gelation was attempted by using amino acid-based sulfamides with the general structure Aa-NH-SO 2 -NH-Aa (Aa=amino acid). A preference for 1D assembly alone was not a sufficient condition for gelation, which became evident from studies involving sulfamide esters 1-5. Reducing the crystallization tendency without hindering unidirectional growth was executed through diacids of the sulfamide precursors with various amines that form an envelope around the sulfamide core through salt bridges. This strategy was fruitful, and gels of a wide variety of solvents could be formed by varying the acid and amine components. The use of dodecylamine or benzylamine, which could stabilize the molecular layers through alkyl-chain segregation or π-π interactions improved the gelation tendency, whereas the nature of the amino acid side chain, especially the rotational freedom and hydrophobicity, had a direct role in dictating the solvent preference. Crystallographic studies of these two-component systems gave molecular-level insight into the assembly and showed the importance of anisotropy in the distribution of secondary interactions in gelation. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

SPINE: SParse eIgengene NEtwork linking gene expression clusters in Dehalococcoides mccartyi to perturbations in experimental conditions

DOE PAGES

Mansfeldt, Cresten B.; Logsdon, Benjamin A.; Debs, Garrett E.; ...

2015-02-25

We present a statistical model designed to identify the effect of experimental perturbations on the aggregate behavior of the transcriptome expressed by the bacterium Dehalococcoides mccartyi strain 195. Strains of Dehalococcoides are used in sub-surface bioremediation applications because they organohalorespire tetrachloroethene and trichloroethene (common chlorinated solvents that contaminate the environment) to non-toxic ethene. However, the biochemical mechanism of this process remains incompletely described. Additionally, the response of Dehalococcoides to stress-inducing conditions that may be encountered at field-sites is not well understood. The constructed statistical model captured the aggregate behavior of gene expression phenotypes by modeling the distinct eigengenes of 100more » transcript clusters, determining stable relationships among these clusters of gene transcripts with a sparse network-inference algorithm, and directly modeling the effect of changes in experimental conditions by constructing networks conditioned on the experimental state. Based on the model predictions, we discovered new response mechanisms for DMC, notably when the bacterium is exposed to solvent toxicity. The network identified a cluster containing thirteen gene transcripts directly connected to the solvent toxicity condition. Transcripts in this cluster include an iron-dependent regulator (DET0096-97) and a methylglyoxal synthase (DET0137). To validate these predictions, additional experiments were performed. Continuously fed cultures were exposed to saturating levels of tetrachloethene, thereby causing solvent toxicity, and transcripts that were predicted to be linked to solvent toxicity were monitored by quantitative reverse-transcription polymerase chain reaction. Twelve hours after being shocked with saturating levels of tetrachloroethene, the control transcripts (encoding for a key hydrogenase and the 16S rRNA) did not significantly change. By contrast, transcripts for DET0137 and DET0097 displayed a 46.8±11.5 and 14.6±9.3 fold up-regulation, respectively, supporting the model. This is the first study to identify transcripts in Dehalococcoides that potentially respond to tetrachloroethene solvent-toxicity conditions that may be encountered near contamination source zones in sub-surface environments.« less

Comparison of the structural basis for thermal stability between archaeal and bacterial proteins.

PubMed

Ding, Yanrui; Cai, Yujie; Han, Yonggang; Zhao, Bingqiang

2012-01-01

In this study, the structural basis for thermal stability in archaeal and bacterial proteins was investigated. There were many common factors that confer resistance to high temperature in both archaeal and bacterial proteins. These factors include increases in the Lys content, the bends and blanks of secondary structure, the Glu content of salt bridge; decreases in the number of main-side chain hydrogen bond and exposed surface area, and changes in the bends and blanks of amino acids. Certainly, the utilization of charged amino acids to form salt bridges is a primary factor. In both heat-resistant archaeal and bacterial proteins, most Glu and Asp participate in the formation of salt bridges. Other factors may influence either archaeal or bacterial protein thermostability, which includes the more frequent occurrence of shorter 3(10)-helices and increased hydrophobicity in heat-resistant archaeal proteins. However, there were increases in average helix length, the Glu content in salt bridges, temperature factors and decreases in the number of main-side chain hydrogen bonds, uncharged-uncharged hydrogen bonds, hydrophobicity, and buried and exposed polar surface area in heat-resistant bacterial proteins. Evidently, there are few similarities and many disparities between the heat-resistant mechanisms of archaeal and bacterial proteins.

Self-assembly of organogels via new luminol imide derivatives: diverse nanostructures and substituent chain effect

PubMed Central

2013-01-01

Luminol is considered as an efficient sycpstem in electrochemiluminescence (ECL) measurements for the detection of hydrogen peroxide. In this paper, new luminol imide derivatives with different alkyl substituent chains were designed and synthesized. Their gelation behaviors in 26 solvents were tested as novel low molecular mass organic gelators. It was shown that the length and number of alkyl substituent chains linked to a benzene ring in gelators played a crucial role in the gelation behavior of all compounds in various organic solvents. Longer alkyl chains in molecular skeletons in present gelators are favorable for the gelation of organic solvents. Scanning electron microscope and atomic force microscope observations revealed that the gelator molecules self-assemble into different micro/nanoscale aggregates from a dot, flower, belt, rod, and lamella to wrinkle with change of solvents. Spectral studies indicated that there existed different H-bond formations and hydrophobic forces, depending on the alkyl substituent chains in molecular skeletons. The present work may give some insight to the design and characteristic of new versatile soft materials and potential ECL biosensors with special molecular structures. PMID:23758979

Self-assembly of organogels via new luminol imide derivatives: diverse nanostructures and substituent chain effect

NASA Astrophysics Data System (ADS)

Jiao, Tifeng; Huang, Qinqin; Zhang, Qingrui; Xiao, Debao; Zhou, Jingxin; Gao, Faming

2013-06-01

Luminol is considered as an efficient sycpstem in electrochemiluminescence (ECL) measurements for the detection of hydrogen peroxide. In this paper, new luminol imide derivatives with different alkyl substituent chains were designed and synthesized. Their gelation behaviors in 26 solvents were tested as novel low molecular mass organic gelators. It was shown that the length and number of alkyl substituent chains linked to a benzene ring in gelators played a crucial role in the gelation behavior of all compounds in various organic solvents. Longer alkyl chains in molecular skeletons in present gelators are favorable for the gelation of organic solvents. Scanning electron microscope and atomic force microscope observations revealed that the gelator molecules self-assemble into different micro/nanoscale aggregates from a dot, flower, belt, rod, and lamella to wrinkle with change of solvents. Spectral studies indicated that there existed different H-bond formations and hydrophobic forces, depending on the alkyl substituent chains in molecular skeletons. The present work may give some insight to the design and characteristic of new versatile soft materials and potential ECL biosensors with special molecular structures.

Color vision impairments among shipyard workers exposed to mixed organic solvents, especially xylene.

PubMed

Lee, Eun-Hee; Paek, Domyung; Kho, Young Lim; Choi, Kyungho; Chae, Hong Jae

2013-01-01

We evaluated color vision impairment in workers exposed to organic solvents, especially xylene. Three groups of subjects, comprising 63 workers occupationally exposed to organic solvents, 122 non-exposed workers in the same industry, and 185 subjects from the general population as controls, were evaluated for color vision. Exposure to solvents was indirectly evaluated by measuring the concentration of a urinary metabolite. Color vision was assessed using the Lanthony Desaturated 15-hue (Lanthony D-15) panel. Color confusion index (CCI) values in the exposed group were significantly higher than in the non-exposed workers or the general population, after adjustment for age and education, and significantly correlated with the concentration of methylhippuric acid. Color vision impairments were detected more frequently among the exposed group, and the most common types were type III and complex impairments. The rate of type III impairments was 9.52% in the exposed group, 1.64% in the non-exposed group, and 1.62% in the general population. Our results support the hypothesis that acquired color vision impairments could be induced by exposure to xylene. Testing for color vision impairment is a relatively simple, non-invasive and sensitive diagnostic method for relatively low-level exposures to xylene. Copyright © 2013 Elsevier Inc. All rights reserved.

The three-dimensional structure of a complex of a murine Fab (NC10. 14) with a potent sweetener (NC174): an illustration of structural diversity in antigen recognition by immunoglobulins.

PubMed

Guddat, L W; Shan, L; Broomell, C; Ramsland, P A; Fan, Z; Anchin, J M; Linthicum, D S; Edmundson, A B

2000-09-29

The three-dimensional structure of a complex of an Fab from a murine IgG2b(lambda) antibody (NC10.14) with a high potency sweet tasting hap- ten, N-(p-cyanophenyl)-N'-(diphenylmethyl)-N"-(carboxymethyl)guan idine (NC174), has been determined to 2.6 A resolution by X-ray crystallography. This complex crystallized in the triclinic space group P1, with two molecules in the asymmetric unit. In contrast to a companion monoclonal antibody (NC6.8) with a kappa-type light chain and similar high affinity for the NC174 ligand, the NC10.14 antibody possessed a large and deep antigen combining site bounded primarily by the third complementarity-determining regions (CDR3s) of the light and heavy chains. CDR3 of the heavy chain dominated the site and its crown protruded into the external solvent as a type 1' beta-turn. NC174 was nested against HCDR3 and was held in place by two tryptophan side-chains (L91 and L96) from LCDR3. The diphenyl rings were accommodated on an upper tier of the binding pocket that is largely hydrophobic. At the floor of the site, a positively charged arginine side-chain (H95) stabilized the orientation of the electronegative cyano group of the hapten. The negative charge on the acetate group was partially neutralized by a hydrogen bond with the phenolic hydroxyl group of tyrosine H58. Comparisons of the modes of binding of NC174 to the NC6.8 and NC10.14 antibodies illustrate the enormous structural and mechanistic diversity manifest by immune responses. Copyright 2000 Academic Press.

Interfacial free energy governs single polystyrene chain collapse in water and aqueous solutions.

PubMed

Li, Isaac T S; Walker, Gilbert C

2010-05-12

The hydrophobic interaction is significantly responsible for driving protein folding and self-assembly. To understand it, the thermodynamics, the role of water structure, the dewetting process surrounding hydrophobes, and related aspects have undergone extensive investigations. Here, we examine the hypothesis that polymer-solvent interfacial free energy is adequate to describe the energetics of the collapse of a hydrophobic homopolymer chain at fixed temperature, which serves as a much simplified model for studying the hydrophobic collapse of a protein. This implies that changes in polymer-solvent interfacial free energy should be directly proportional to the force to extend a collapsed polymer into a bad solvent. To test this hypothesis, we undertook single-molecule force spectroscopy on a collapsed, single, polystyrene chain in water-ethanol and water-salt mixtures where we measured the monomer solvation free energy from an ensemble average conformations. Different proportions within the binary mixture were used to create solvents with different interfacial free energies with polystyrene. In these mixed solvents, we observed a linear correlation between the interfacial free energy and the force required to extend the chain into solution, which is a direct measure of the solvation free energy per monomer on a single chain at room temperature. A simple analytical model compares favorably with the experimental results. This knowledge supports a common assumption that explicit water solvent may not be necessary for cases whose primary concerns are hydrophobic interactions and hydrophobic hydration.

Macromolecular 'size' and 'hardness' drives structure in solvent-swollen blends of linear, cyclic, and star polymers.

PubMed

Gartner, Thomas E; Jayaraman, Arthi

2018-01-17

In this paper, we apply molecular simulation and liquid state theory to uncover the structure and thermodynamics of homopolymer blends of the same chemistry and varying chain architecture in the presence of explicit solvent species. We use hybrid Monte Carlo (MC)/molecular dynamics (MD) simulations in the Gibbs ensemble to study the swelling of ∼12 000 g mol -1 linear, cyclic, and 4-arm star polystyrene chains in toluene. Our simulations show that the macroscopic swelling response is indistinguishable between the various architectures and matches published experimental data for the solvent annealing of linear polystyrene by toluene vapor. We then use standard MD simulations in the NPT ensemble along with polymer reference interaction site model (PRISM) theory to calculate effective polymer-solvent and polymer-polymer Flory-Huggins interaction parameters (χ eff ) in these systems. As seen in the macroscopic swelling results, there are no significant differences in the polymer-solvent and polymer-polymer χ eff between the various architectures. Despite similar macroscopic swelling and effective interaction parameters between various architectures, the pair correlation function between chain centers-of-mass indicates stronger correlations between cyclic or star chains in the linear-cyclic blends and linear-star blends, compared to linear chain-linear chain correlations. Furthermore, we note striking similarities in the chain-level correlations and the radius of gyration of cyclic and 4-arm star architectures of identical molecular weight. Our results indicate that the cyclic and star chains are 'smaller' and 'harder' than their linear counterparts, and through comparison with MD simulations of blends of soft spheres with varying hardness and size we suggest that these macromolecular characteristics are the source of the stronger cyclic-cyclic and star-star correlations.

Two-dimensional sup 1 H nuclear magnetic resonance study of AaH IT, an anti-insect toxin from the scorpion Androctonus australis Hector. Sequential resonance assignments and folding of the polypeptide chain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Darbon, H.; Weber, C.; Braun, W.

1991-02-19

Sequence-specific nuclear magnetic resonance assignments for the polypeptide backbone and for most of the amino acid side-chain protons, as well as the general folding of AaH IT, are described. AaH IT is a neurotoxin purified from the venom of the scorpion Androctonus australis Hector and is specifically active on the insect nervous system. The secondary structure and the hydrogen-bonding patterns in the regular secondary structure elements are deduced from nuclear Overhauser effects and the sequence locations of the slowly exchanging amide protons. The backbone folding is determined by distance geometry calculations with the DISMAN program. The regular secondary structure includesmore » two and a half turns of {alpha}-helix running from residues 21 to 30 and a three-stranded antiparallel {beta}-sheet including peptides 3-5, 34-38, and 41-46. Two tight turns are present, one connecting the end of the {alpha}-helix to an external strand of the {beta}-sheet, i.e., turn 31-34, and another connecting this same strand to the central one, i.e., turn 38-41. The differences in the specificity of these related proteins, which are able to discriminate between mammalian and insect voltage-dependent sodium channels of excitable tissues, are most probably brought about by the position of the C-terminal peptide with regard to a hydrophobic surface common to all scorpion toxins examined thus far. Thus, the interaction of a given scorpion toxin with its receptor might well be governed by the presence of this solvent-exposed hydrophobic surface, whereas adjacent areas modulate the specificity of the interaction.« less

Chronic Organic Solvent Exposure Changes Visual Tracking in Men and Women.

PubMed

de Oliveira, Ana R; Campos Neto, Armindo de Arruda; Bezerra de Medeiros, Paloma C; de Andrade, Michael J O; Dos Santos, Natanael A

2017-01-01

Organic solvents can change CNS sensory and motor function. Eye-movement analyses can be important tools when investigating the neurotoxic changes that result from chronic organic solvent exposure. The current research measured the eye-movement patterns of men and women with and without histories of chronic organic solvent exposure. A total of 44 volunteers between 18 and 41 years old participated in this study; 22 were men (11 exposed and 11 controls), and 22 were women (11 exposed and 11 controls). Eye movement was evaluated using a 250-Hz High-Speed Video Eye Tracker Toolbox (Cambridge Research Systems) via an image of a maze. Specific body indices of exposed and non-exposed men and women were measured with an Inbody 720 to determine whether the differences in eye-movement patterns were associated with body composition. The data were analyzed using IBM SPSS Statistics version 20.0.0. The results indicated that exposed adults showed significantly more fixations ( t = 3.82; p = 0.001; r = 0.51) and longer fixations ( t = 4.27; p = 0.001, r = 0.54) than their non-exposed counterparts. Comparisons within men (e.g., exposed and non-exposed) showed significant differences in the number of fixations ( t = 2.21; p = 0.04; r = 0.20) and duration of fixations ( t = 3.29; p = 0.001; r = 0.35). The same was true for exposed vs. non-exposed women, who showed significant differences in the number of fixations ( t = 3.10; p = 0.001; r = 0.32) and fixation durations ( t = 2.76; p = 0.01; r = 0.28). However, the results did not show significant differences between exposed women and men in the number and duration of fixations. No correlations were found between eye-movement pattern and body composition measures ( p > 0.05). These results suggest that chronic organic solvent exposure affects eye movements, regardless of sex and body composition, and that eye tracking contributes to the investigation of the visual information processing disorders acquired by workers exposed to organic solvents.

Changes in conformational dynamics of basic side chains upon protein–DNA association

PubMed Central

Esadze, Alexandre; Chen, Chuanying; Zandarashvili, Levani; Roy, Sourav; Pettitt, B. Montgometry; Iwahara, Junji

2016-01-01

Basic side chains play major roles in recognition of nucleic acids by proteins. However, dynamic properties of these positively charged side chains are not well understood. In this work, we studied changes in conformational dynamics of basic side chains upon protein–DNA association for the zinc-finger protein Egr-1. By nuclear magnetic resonance (NMR) spectroscopy, we characterized the dynamics of all side-chain cationic groups in the free protein and in the complex with target DNA. Our NMR order parameters indicate that the arginine guanidino groups interacting with DNA bases are strongly immobilized, forming rigid interfaces. Despite the strong short-range electrostatic interactions, the majority of the basic side chains interacting with the DNA phosphates exhibited high mobility, forming dynamic interfaces. In particular, the lysine side-chain amino groups exhibited only small changes in the order parameters upon DNA-binding. We found a similar trend in the molecular dynamics (MD) simulations for the free Egr-1 and the Egr-1–DNA complex. Using the MD trajectories, we also analyzed side-chain conformational entropy. The interfacial arginine side chains exhibited substantial entropic loss upon binding to DNA, whereas the interfacial lysine side chains showed relatively small changes in conformational entropy. These data illustrate different dynamic characteristics of the interfacial arginine and lysine side chains. PMID:27288446

Structural basis of light chain amyloidogenicity: comparison of the thermodynamic properties, fibrillogenic potential and tertiary structural features of four vλ6 proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wall, J.S.; Gupta, V.; Wilkerson, M.

2004-04-01

Primary (AL) amyloidosis results from the pathologic deposition of monoclonal light chains as amyloid fibrils. Studies of recombinant-derived variable region (V{sub L}) fragments of these proteins have shown an inverse relationship between thermodynamic stability and fibrillogenic potential. Further, ionic interactions within the V{sub L} domain were predicted to influence the kinetics of light chain fibrillogenicity, as evidenced from our analyses of a relatively stable V{sub {lambda}}6 protein (Jto) with a long range electrostatic interaction between Asp and Arg side chains at position 29 and 68, respectively, and an unstable, highly fibrillogenic V{sub {lambda}}6 protein (Wil) that had neutral amino acidsmore » at these locations. To test this hypothesis, we have generated two Jto-related mutants designed to disrupt the interaction between Asp 29 and Arg 68 (JtoD29A and JtoR68S). Although the thermodynamic stabilities of unfolding for these two molecules were identical, they exhibited very different kinetics of fibril formation: the rate of JtoD29A fibrillogenesis was slow and comparable to the parent molecule, whereas that of JtoR68S was significantly faster. High-resolution X-ray diffraction analyses of crystals prepared from the two mutants having the same space group and unit cell dimensions revealed no significant main-chain conformational changes. However, several notable side-chain alterations were observed in JtoR68S, as compared with JtoD29A, that resulted in the solvent exposure of a greater hydrophobic surface and modifications in the electrostatic potential surface. We posit that these differences contributed to the enhanced fibrillogenic potential of the Arg 68 mutant, since both Jto mutants lacked the intrachain ionic interaction and were equivalently unstable. The information gleaned from our studies has provided insight into structural parameters that in addition to overall thermodynamic stability, contribute to the fibril forming propensity of immunoglobulin light chains.« less

Comment on "Relating side chain organization of PNIPAm with its conformation in aqueous methanol" by D. Mukherji, M. Wagner, M. D. Watson, S. Winzen, T. E. de Oliveira, C. M. Marques and K. Kremer, Soft Matter, 2016, 12, 7995.

PubMed

Pica, Andrea; Graziano, Giuseppe

2017-11-01

In a recent article, Kremer and co-workers have combined NMR measurements and very long, all-atom MD simulations to strengthen their original claim that PNIPAM cononsolvency in water-methanol solutions is driven by the ability of MeOH molecules to bridge different monomers far away along the polymeric chain. In this comment, the results presented by Kremer and co-workers are reviewed, analyzed, and questioned regarding their ability to provide support to the bridging mechanism. Here, some pieces of evidence are provided to show that: (1) the solvent-excluded volume effect plays always a fundamental role in polymer collapse; (2) PNIPAM cononsolvency is caused by the geometric-energetic frustration experienced by the polymer when it can interact with both water and methanol molecules at the same time.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Los Alamos National Laboratory, Mailstop M888, Los Alamos, NM 87545, USA; Lawrence Berkeley National Laboratory, One Cyclotron Road, Building 64R0121, Berkeley, CA 94720, USA; Department of Haematology, University of Cambridge, Cambridge CB2 0XY, England

The PHENIX AutoBuild Wizard is a highly automated tool for iterative model-building, structure refinement and density modification using RESOLVE or TEXTAL model-building, RESOLVE statistical density modification, and phenix.refine structure refinement. Recent advances in the AutoBuild Wizard and phenix.refine include automated detection and application of NCS from models as they are built, extensive model completion algorithms, and automated solvent molecule picking. Model completion algorithms in the AutoBuild Wizard include loop-building, crossovers between chains in different models of a structure, and side-chain optimization. The AutoBuild Wizard has been applied to a set of 48 structures at resolutions ranging from 1.1 {angstrom} tomore » 3.2 {angstrom}, resulting in a mean R-factor of 0.24 and a mean free R factor of 0.29. The R-factor of the final model is dependent on the quality of the starting electron density, and relatively independent of resolution.« less

Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard.

PubMed

Terwilliger, Thomas C; Grosse-Kunstleve, Ralf W; Afonine, Pavel V; Moriarty, Nigel W; Zwart, Peter H; Hung, Li Wei; Read, Randy J; Adams, Paul D

2008-01-01

The PHENIX AutoBuild wizard is a highly automated tool for iterative model building, structure refinement and density modification using RESOLVE model building, RESOLVE statistical density modification and phenix.refine structure refinement. Recent advances in the AutoBuild wizard and phenix.refine include automated detection and application of NCS from models as they are built, extensive model-completion algorithms and automated solvent-molecule picking. Model-completion algorithms in the AutoBuild wizard include loop building, crossovers between chains in different models of a structure and side-chain optimization. The AutoBuild wizard has been applied to a set of 48 structures at resolutions ranging from 1.1 to 3.2 A, resulting in a mean R factor of 0.24 and a mean free R factor of 0.29. The R factor of the final model is dependent on the quality of the starting electron density and is relatively independent of resolution.

Health effects of long-term solvent exposure among women in blue-collar occupations.

PubMed

Parkinson, D K; Bromet, E J; Cohen, S; Dunn, L O; Dew, M A; Ryan, C; Schwartz, J E

1990-01-01

The relationship of solvent exposure to self-reported neurologic and somatic symptoms as well as neuropsychological performance was examined in a sample of 567 female blue collar workers who were members of the International Brotherhood of Electrical Workers (IBEW). Structured interviews were conducted at IBEW offices. Five solvent exposure categories were derived--never exposed, exposed prior to but not during the past year, exposed during the past year but not currently, currently exposed less than 50% of the time, and currently exposed more than 50% of the time. No differences among the groups on neuropsychological performance were found. On the other hand, heightened exposure was significantly related to depression, severe headaches, light-headedness, room spinning, appetite difficulties, funny taste in mouth, weakness/fatigue, rashes, and abdominal pain after controlling for the effects of seven risk factors (age, smoking, moderate-heavy alcohol consumption, severe obesity, history of physician-diagnosed chronic illness, working in a clean room, and exposure to other chemicals). These findings are consistent with Scandinavian studies of solvent-exposed male workers and point to the need for careful prospective research.

Solution-Phase Conformation and Dynamics of Conjugated Isoindigo-Based Donor–Acceptor Polymer Single Chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Franklin L.; Farimani, Amir Barati; Gu, Kevin L.

Conjugated polymers are the key material in thin-film organic optoelectronic devices due to the versatility of these molecules combined with their semiconducting properties. A molecular-scale understanding of conjugated polymers is important to the optimization of the thin-film morphology. We examine the solution-phase behavior of conjugated isoindigo-based donor–acceptor polymer single chains of various chain lengths using atomistic molecular dynamics simulations. Our simulations elucidate the transition from a rod-like to a coil-like conformation from an analysis of normal modes and persistence length. In addition, we find another transition based on the solvent environment, contrasting the coil-like conformation in a good solvent withmore » a globule-like conformation in a poor solvent. Altogether, our results provide valuable insights into the transition between conformational regimes for conjugated polymers as a function of both the chain length and the solvent environment, which will help to accurately parametrize higher level models.« less

Solution-Phase Conformation and Dynamics of Conjugated Isoindigo-Based Donor–Acceptor Polymer Single Chains

DOE PAGES

Lee, Franklin L.; Farimani, Amir Barati; Gu, Kevin L.; ...

2017-10-25

Conjugated polymers are the key material in thin-film organic optoelectronic devices due to the versatility of these molecules combined with their semiconducting properties. A molecular-scale understanding of conjugated polymers is important to the optimization of the thin-film morphology. We examine the solution-phase behavior of conjugated isoindigo-based donor–acceptor polymer single chains of various chain lengths using atomistic molecular dynamics simulations. Our simulations elucidate the transition from a rod-like to a coil-like conformation from an analysis of normal modes and persistence length. In addition, we find another transition based on the solvent environment, contrasting the coil-like conformation in a good solvent withmore » a globule-like conformation in a poor solvent. Altogether, our results provide valuable insights into the transition between conformational regimes for conjugated polymers as a function of both the chain length and the solvent environment, which will help to accurately parametrize higher level models.« less

Configurations and Dynamics of Semi-Flexible Polymers in Good and Poor Solvents

NASA Astrophysics Data System (ADS)

Larson, Ronald

We develop coarse-graining procedures for determining the conformational and dynamic behavior of semi-flexible chains with and without flow using Brownian dynamics (BD) simulations that are insensitive to the degree of coarse-graining. In the absence of flow, in a poor solvent, we find three main collapsed states: torus, bundle, and globule over a range of dimensionless ratios of the three energy parameters, namely solvent-polymer surface energy, energy of polymer folds, and polymer bending energy or persistence length. A theoretical phase diagram, confirmed by BD simulations, captures the general phase behavior of a single long chain (>10 Kuhn lengths) at moderately high (order unity) dimensionless temperature, which is the ratio of thermal energy to the attractive interaction between neighboring monomers. We also find converged results for polymer conformations in shear or extensional flow in solvents of various qualities and determine scaling laws for chain dimensions for low, moderate, and high Weissenberg numbers Wi. We also derive scaling laws to describe chains dimensions and tumbling rates in these regimes.

An improved approach to the analysis of drug-protein binding by distance geometry

NASA Technical Reports Server (NTRS)

Goldblum, A.; Kieber-Emmons, T.; Rein, R.

1986-01-01

The calculation of side chain centers of coordinates and the subsequent generation of side chain-side chain and side chain-backbone distance matrices is suggested as an improved method for viewing interactions inside proteins and for the comparison of protein structures. The use of side chain distance matrices is demonstrated with free PTI, and the use of difference distance matrices for side chains is shown for free and trypsin-bound PTI as well as for the X-ray structures of trypsin complexes with PTI and with benzamidine. It is found that conformational variations are reflected in the side chain distance matrices much more than in the standard C-C distance representations.

Improvement of activity and stability of chloroperoxidase by chemical modification

PubMed Central

Liu, Jian-Zhong; Wang, Min

2007-01-01

Background Enzymes show relative instability in solvents or at elevated temperature and lower activity in organic solvent than in water. These limit the industrial applications of enzymes. Results In order to improve the activity and stability of chloroperoxidase, chloroperoxidase was modified by citraconic anhydride, maleic anhydride or phthalic anhydride. The catalytic activities, thermostabilities and organic solvent tolerances of native and modified enzymes were compared. In aqueous buffer, modified chloroperoxidases showed similar Km values and greater catalytic efficiencies kcat/Km for both sulfoxidation and oxidation of phenol compared to native chloroperoxidase. Of these modified chloroperoxidases, citraconic anhydride-modified chloroperoxidase showed the greatest catalytic efficiency in aqueous buffer. These modifications of chloroperoxidase increased their catalytic efficiencies for sulfoxidation by 12%~26% and catalytic efficiencies for phenol oxidation by 7%~53% in aqueous buffer. However, in organic solvent (DMF), modified chloroperoxidases had lower Km values and higher catalytic efficiencies kcat/Km than native chloroperoxidase. These modifications also improved their thermostabilities by 1~2-fold and solvent tolerances of DMF. CD studies show that these modifications did not change the secondary structure of chloroperoxidase. Fluorescence spectra proved that these modifications changed the environment of tryptophan. Conclusion Chemical modification of epsilon-amino groups of lysine residues of chloroperoxidase using citraconic anhydride, maleic anhydride or phthalic anhydride is a simple and powerful method to enhance catalytic properties of enzyme. The improvements of the activity and stability of chloroperoxidase are related to side chain reorientations of aromatics upon both modifications. PMID:17511866

The role of different structural motifs in the ultrafast dynamics of second generation protein stains.

PubMed

Chatterjee, Soumit; Karuso, Peter; Boulangé, Agathe; Peixoto, Philippe A; Franck, Xavier; Datta, Anindya

2013-12-05

Engineering the properties of fluorescent probes through modifications of the fluorophore structure has become a subject of interest in recent times. By doing this, the photophysical and photochemical properties of the modified fluorophore can be understood and this can guide the design and synthesis of better fluorophores for use in biotechnology. In this work, the electronic spectra and fluorescence decay kinetics of four analogues of the fluorescent natural product epicocconone were investigated. Epicocconone is unique in that the native state is weakly green fluorescent, whereas the enamine formed reversibly with proteins is highly emissive in the red. It was found that the ultrafast dynamics of the analogues depends profoundly on the H-bonding effect of solvents and solvent viscosity though solvent polarity also plays a role. Comparing the steady state and time-resolved data, the weak fluorescence of epicocconone in its native state is most likely due to the photoisomerization of the hydrocarbon side chain, while the keto enol moiety also has a role to play in determining the fluorescence quantum yield. This understanding is expected to aid the design of better protein stains from the same family.

Neutron Crystallography for the Study of Hydrogen Bonds in Macromolecules.

PubMed

Oksanen, Esko; Chen, Julian C-H; Fisher, Suzanne Zoë

2017-04-07

Abstract : The hydrogen bond (H bond) is one of the most important interactions that form the foundation of secondary and tertiary protein structure. Beyond holding protein structures together, H bonds are also intimately involved in solvent coordination, ligand binding, and enzyme catalysis. The H bond by definition involves the light atom, H, and it is very difficult to study directly, especially with X-ray crystallographic techniques, due to the poor scattering power of H atoms. Neutron protein crystallography provides a powerful, complementary tool that can give unambiguous information to structural biologists on solvent organization and coordination, the electrostatics of ligand binding, the protonation states of amino acid side chains and catalytic water species. The method is complementary to X-ray crystallography and the dynamic data obtainable with NMR spectroscopy. Also, as it gives explicit H atom positions, it can be very valuable to computational chemistry where exact knowledge of protonation and solvent orientation can make a large difference in modeling. This article gives general information about neutron crystallography and shows specific examples of how the method has contributed to structural biology, structure-based drug design; and the understanding of fundamental questions of reaction mechanisms.

Neutron crystallography for the study of hydrogen bonds in macromolecules

DOE PAGES

Oksanen, Esko; Chen, Julian C.; Fisher, Zoe

2017-04-07

The hydrogen bond (H bond) is one of the most important interactions that form the foundation of secondary and tertiary protein structure. Beyond holding protein structures together, H bonds are also intimately involved in solvent coordination, ligand binding, and enzyme catalysis. The H bond by definition involves the light atom, H, and it is very difficult to study directly, especially with X-ray crystallographic techniques, due to the poor scattering power of H atoms. Neutron protein crystallography provides a powerful, complementary tool that can give unambiguous information to structural biologists on solvent organization and coordination, the electrostatics of ligand binding, themore » protonation states of amino acid side chains and catalytic water species. The method is complementary to X-ray crystallography and the dynamic data obtainable with NMR spectroscopy. Also, as it gives explicit H atom positions, it can be very valuable to computational chemistry where exact knowledge of protonation and solvent orientation can make a large difference in modeling. Finally, this article gives general information about neutron crystallography and shows specific examples of how the method has contributed to structural biology, structure-based drug design; and the understanding of fundamental questions of reaction mechanisms.« less

Neutron crystallography for the study of hydrogen bonds in macromolecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oksanen, Esko; Chen, Julian C.; Fisher, Zoe

The hydrogen bond (H bond) is one of the most important interactions that form the foundation of secondary and tertiary protein structure. Beyond holding protein structures together, H bonds are also intimately involved in solvent coordination, ligand binding, and enzyme catalysis. The H bond by definition involves the light atom, H, and it is very difficult to study directly, especially with X-ray crystallographic techniques, due to the poor scattering power of H atoms. Neutron protein crystallography provides a powerful, complementary tool that can give unambiguous information to structural biologists on solvent organization and coordination, the electrostatics of ligand binding, themore » protonation states of amino acid side chains and catalytic water species. The method is complementary to X-ray crystallography and the dynamic data obtainable with NMR spectroscopy. Also, as it gives explicit H atom positions, it can be very valuable to computational chemistry where exact knowledge of protonation and solvent orientation can make a large difference in modeling. Finally, this article gives general information about neutron crystallography and shows specific examples of how the method has contributed to structural biology, structure-based drug design; and the understanding of fundamental questions of reaction mechanisms.« less

Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels

PubMed Central

Armstrong, Craig T.; Mason, Philip E.; Anderson, J. L. Ross; Dempsey, Christopher E.

2016-01-01

Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD. PMID:26899474

Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels

NASA Astrophysics Data System (ADS)

Armstrong, Craig T.; Mason, Philip E.; Anderson, J. L. Ross; Dempsey, Christopher E.

2016-02-01

Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD.

Direct Investigation of Slow Correlated Dynamics in Proteins via Dipolar Interactions

PubMed Central

Fenwick, R. Bryn; Schwieters, Charles D.; Vögeli, Beat

2016-01-01

The synchronization of native state motions as they transition between microstates influences catalysis kinetics, mediates allosteric interactions and reduces the conformational entropy of proteins. However, it has proven difficult to describe native microstates because they are usually minimally frustrated and may interconvert on the μs-ms time scale. Direct observation of concerted equilibrium fluctuations would therefore be an important tool for describing protein native states. Here we propose a strategy that relates NMR cross-correlated relaxation (CCR) rates between dipolar interactions to residual dipolar couplings (RDCs) of individual consecutive HN–N and Hα–Cα bonds, which act as a proxy for the peptide planes and the side chains respectively. Using Xplor-NIH ensemble structure calculations restrained with the RDC and CCR data we observe collective motions on time scales slower than nanoseconds in the backbone for GB3. To directly access the correlations from CCR we develop a structure-free data analysis. The resulting dynamic correlation map is consistent with the ensemble-restrained simulations and reveals a complex network. In general we find that the bond motions are on average slightly correlated, and that the local environment dominates many observations. Despite this, some patterns are typical over entire secondary structure elements. In the β-sheet, nearly all bonds are weakly correlated and there is an approximately binary alternation in correlation intensity corresponding to the solvent exposure/shielding alternation of the side chains. For α-helices there is also a weak correlation in the HN-N bonds and the degree of correlation involving Hα-Cα bonds is directly affected by side-chain fluctuations, while loops show complex and non-uniform behavior. PMID:27331619

An all-atom structure-based potential for proteins: bridging minimal models with all-atom empirical forcefields.

PubMed

Whitford, Paul C; Noel, Jeffrey K; Gosavi, Shachi; Schug, Alexander; Sanbonmatsu, Kevin Y; Onuchic, José N

2009-05-01

Protein dynamics take place on many time and length scales. Coarse-grained structure-based (Go) models utilize the funneled energy landscape theory of protein folding to provide an understanding of both long time and long length scale dynamics. All-atom empirical forcefields with explicit solvent can elucidate our understanding of short time dynamics with high energetic and structural resolution. Thus, structure-based models with atomic details included can be used to bridge our understanding between these two approaches. We report on the robustness of folding mechanisms in one such all-atom model. Results for the B domain of Protein A, the SH3 domain of C-Src Kinase, and Chymotrypsin Inhibitor 2 are reported. The interplay between side chain packing and backbone folding is explored. We also compare this model to a C(alpha) structure-based model and an all-atom empirical forcefield. Key findings include: (1) backbone collapse is accompanied by partial side chain packing in a cooperative transition and residual side chain packing occurs gradually with decreasing temperature, (2) folding mechanisms are robust to variations of the energetic parameters, (3) protein folding free-energy barriers can be manipulated through parametric modifications, (4) the global folding mechanisms in a C(alpha) model and the all-atom model agree, although differences can be attributed to energetic heterogeneity in the all-atom model, and (5) proline residues have significant effects on folding mechanisms, independent of isomerization effects. Because this structure-based model has atomic resolution, this work lays the foundation for future studies to probe the contributions of specific energetic factors on protein folding and function.

An All-atom Structure-Based Potential for Proteins: Bridging Minimal Models with All-atom Empirical Forcefields

PubMed Central

Whitford, Paul C.; Noel, Jeffrey K.; Gosavi, Shachi; Schug, Alexander; Sanbonmatsu, Kevin Y.; Onuchic, José N.

2012-01-01

Protein dynamics take place on many time and length scales. Coarse-grained structure-based (Gō) models utilize the funneled energy landscape theory of protein folding to provide an understanding of both long time and long length scale dynamics. All-atom empirical forcefields with explicit solvent can elucidate our understanding of short time dynamics with high energetic and structural resolution. Thus, structure-based models with atomic details included can be used to bridge our understanding between these two approaches. We report on the robustness of folding mechanisms in one such all-atom model. Results for the B domain of Protein A, the SH3 domain of C-Src Kinase and Chymotrypsin Inhibitor 2 are reported. The interplay between side chain packing and backbone folding is explored. We also compare this model to a Cα structure-based model and an all-atom empirical forcefield. Key findings include 1) backbone collapse is accompanied by partial side chain packing in a cooperative transition and residual side chain packing occurs gradually with decreasing temperature 2) folding mechanisms are robust to variations of the energetic parameters 3) protein folding free energy barriers can be manipulated through parametric modifications 4) the global folding mechanisms in a Cα model and the all-atom model agree, although differences can be attributed to energetic heterogeneity in the all-atom model 5) proline residues have significant effects on folding mechanisms, independent of isomerization effects. Since this structure-based model has atomic resolution, this work lays the foundation for future studies to probe the contributions of specific energetic factors on protein folding and function. PMID:18837035

Orientation-dependent potential of mean force for protein folding

NASA Astrophysics Data System (ADS)

Mukherjee, Arnab; Bhimalapuram, Prabhakar; Bagchi, Biman

2005-07-01

We present a solvent-implicit minimalistic model potential among the amino acid residues of proteins, obtained by using the known native structures [deposited in the Protein Data Bank (PDB)]. In this model, the amino acid side chains are represented by a single ellipsoidal site, defined by the group of atoms about the center of mass of the side chain. These ellipsoidal sites interact with other sites through an orientation-dependent interaction potential which we construct in the following fashion. First, the site-site potential of mean force (PMF) between heavy atoms is calculated [following F. Melo and E. Feytsman, J. Mol. Biol. 267, 207 (1997)] from statistics of their distance separation obtained from crystal structures. These site-site potentials are then used to calculate the distance and the orientation-dependent potential between side chains of all the amino acid residues (AAR). The distance and orientation dependencies show several interesting results. For example, we find that the PMF between two hydrophobic AARs, such as phenylalanine, is strongly attractive at short distances (after the obvious repulsive region at very short separation) and is characterized by a deep minimum, for specific orientations. For the interaction between two hydrophilic AARs, such a deep minimum is absent and in addition, the potential interestingly reveals the combined effect of polar (charge) and hydrophobic interactions among some of these AARs. The effectiveness of our potential has been tested by calculating the Z-scores for a large set of proteins. The calculated Z-scores show high negative values for most of them, signifying the success of the potential to identify the native structure from among a large number of its decoy states.

Structure-relaxation mechanism for the response of T4 lysozyme cavity mutants to hydrostatic pressure

PubMed Central

Lerch, Michael T.; López, Carlos J.; Yang, Zhongyu; Kreitman, Margaux J.; Horwitz, Joseph; Hubbell, Wayne L.

2015-01-01

Application of hydrostatic pressure shifts protein conformational equilibria in a direction to reduce the volume of the system. A current view is that the volume reduction is dominated by elimination of voids or cavities in the protein interior via cavity hydration, although an alternative mechanism wherein cavities are filled with protein side chains resulting from a structure relaxation has been suggested [López CJ, Yang Z, Altenbach C, Hubbell WL (2013) Proc Natl Acad Sci USA 110(46):E4306–E4315]. In the present study, mechanisms for elimination of cavities under high pressure are investigated in the L99A cavity mutant of T4 lysozyme and derivatives thereof using site-directed spin labeling, pressure-resolved double electron–electron resonance, and high-pressure circular dichroism spectroscopy. In the L99A mutant, the ground state is in equilibrium with an excited state of only ∼3% of the population in which the cavity is filled by a protein side chain [Bouvignies et al. (2011) Nature 477(7362):111–114]. The results of the present study show that in L99A the native ground state is the dominant conformation to pressures of 3 kbar, with cavity hydration apparently taking place in the range of 2–3 kbar. However, in the presence of additional mutations that lower the free energy of the excited state, pressure strongly populates the excited state, thereby eliminating the cavity with a native side chain rather than solvent. Thus, both cavity hydration and structure relaxation are mechanisms for cavity elimination under pressure, and which is dominant is determined by details of the energy landscape. PMID:25918400

Changes in conformational dynamics of basic side chains upon protein-DNA association.

PubMed

Esadze, Alexandre; Chen, Chuanying; Zandarashvili, Levani; Roy, Sourav; Pettitt, B Montgometry; Iwahara, Junji

2016-08-19

Basic side chains play major roles in recognition of nucleic acids by proteins. However, dynamic properties of these positively charged side chains are not well understood. In this work, we studied changes in conformational dynamics of basic side chains upon protein-DNA association for the zinc-finger protein Egr-1. By nuclear magnetic resonance (NMR) spectroscopy, we characterized the dynamics of all side-chain cationic groups in the free protein and in the complex with target DNA. Our NMR order parameters indicate that the arginine guanidino groups interacting with DNA bases are strongly immobilized, forming rigid interfaces. Despite the strong short-range electrostatic interactions, the majority of the basic side chains interacting with the DNA phosphates exhibited high mobility, forming dynamic interfaces. In particular, the lysine side-chain amino groups exhibited only small changes in the order parameters upon DNA-binding. We found a similar trend in the molecular dynamics (MD) simulations for the free Egr-1 and the Egr-1-DNA complex. Using the MD trajectories, we also analyzed side-chain conformational entropy. The interfacial arginine side chains exhibited substantial entropic loss upon binding to DNA, whereas the interfacial lysine side chains showed relatively small changes in conformational entropy. These data illustrate different dynamic characteristics of the interfacial arginine and lysine side chains. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Comprehensive Study on the Impact of the Cation Alkyl Side Chain Length on the Solubility of Water in Ionic Liquids.

PubMed

Kurnia, Kiki A; Neves, Catarina M S S; Freire, Mara G; Santos, Luís M N B F; Coutinho, João A P

2015-10-01

A comprehensive study on the phase behaviour of two sets of ionic liquids (ILs) and their interactions with water is here presented through combining experimental and theoretical approaches. The impact of the alkyl side chain length and the cation symmetry on the water solubility in the asymmetric [C N- 1 C 1 im][NTf 2 ] and symmetric [C N- 1 C N- 1 im][NTf 2 ] series of ILs ( N up to 22), from 288.15 K to 318.15 K and at atmospheric pressure, was studied. The experimental data reveal that the solubility of water in ILs with an asymmetric cation is higher than in those with the symmetric isomer. Several trend shifts on the water solubility as a function of the alkyl side chain length were identified, namely at [C 6 C 1 im][NTf 2 ] for asymmetric ILs and at [C 4 C 4 im][NTf 2 ] and [C 7 C 7 im][NTf 2 ] for the symmetric ILs. To complement the experimental data and to further investigate the molecular-level mechanisms behind the dissolution process, Density Functional Theory calculations, using the Conductor-like Screening Model for Real Solvents (COSMO-RS) and the Electrostatic potential-derived CHelpG, were performed. The COSMO-RS model is able to qualitatively predict water solubility as function of temperature and alkyl chain lengths of both symmetric and asymmetric cations. Furthermore, the model is also capable to predict the somewhat higher water solubility in the asymmetric cation, as well as the trend shift as function of alkyl chain lengths experimentally observed. Both COSMO-RS and the electrostatic potential-derived CHelpG show that the interactions of water and the IL cation take place on the IL polar region, namely on the aromatic head and adjacent methylene groups what explains the differences in water solubility observed for cations with different chain lengths. Furthermore, the CHelpG calculations for the isolated cations in the gas phase indicates that the trend shift of water solubility as function of alkyl chain lengths and the difference of water solubility in symmetric may also result from the partial positive charge distribution/contribution of the cation.

How does low-molecular-weight polystyrene dissolve: osmotic swelling vs. surface dissolution.

PubMed

Marcon, Valentina; van der Vegt, Nico F A

2014-12-07

By means of multiscale hierarchical modeling we study the real time evolution of low-molecular-weight polystyrene, below the glass transition temperature, in contact with its solvent, toluene. We observe two concurrent phenomena taking place: (1) the solvent diffuses into the polymer by a Case II mechanism, leading to osmotic driven swelling and progressive chain dilution (inside-out mechanism); (2) polymer chains are solvated, detach from the interface and move into the solvent before the film is completely swollen (outside-in mechanism). From our simulations we conclude that, below the entanglement length, a thin swollen layer, also observed in previous experiments, forms almost instantaneously, which allows for the outside-in mechanism to start a few tens of nanoseconds after the polymer-solvent initial contact. After this initial transient time the two mechanisms are concurrent. We furthermore observe that the presence of the solvent significantly enhances the mobility of the polymer chains of the surface layer, but only in the direction parallel to the interface.

Occupational exposure to organic solvents as a cause of sleep apnoea.

PubMed Central

Edling, C; Lindberg, A; Ulfberg, J

1993-01-01

A high prevalence of sleep apnoea was found in a group of men occupationally exposed to organic solvents. Workers with long term exposure to organic solvents often report symptoms such as fatigue, forgetfulness, and concentration difficulties. These symptoms are strikingly similar to those reported by patients with obstructive sleep apnoea syndrome (OSAS). This is a frequently diagnosed disorder characterised by disturbed sleep causing psychic or somatic complications and daytime sleepiness. A study was undertaken to evaluate whether people with long term occupational exposure to organic solvents have a higher prevalence of sleep apnoea than the general population. Patients exposed to solvents (66 men) were invited to participate in a screening for sleep apnoea. A static charge sensitive bed was used for the monitoring of respiration movements and pulse oximetry during one night. A classical sleep apnoea was diagnosed if periodic respiration movement exceeded 45% of estimated sleep time and the oxygen desaturation index exceeded 6. The prevalence of sleep apnoea among the men exposed to solvents was compared with the prevalence in the general population (1.4%). The prevalence among the participating exposed men was 19.7% which gave a conservative relative risk estimate of 14.1 (95% confidence interval (95% CI) 7.5-24.2). The results indicate that exposure to organic solvents causes sleep apnoea. An alternative possibility is that people with sleep apnoea are misdiagnosed as cases of solvent induced toxic encephalopathy. The interpretation has importance for the caring of the patient. PMID:8457496

Preparation of bio-deep eutectic solvent triggered cephalopod shaped silver chloride-DNA hybrid material having antibacterial and bactericidal activity.

PubMed

Bhatt, Jitkumar; Mondal, Dibyendu; Bhojani, Gopal; Chatterjee, Shruti; Prasad, Kamalesh

2015-11-01

2.5% w/w DNA (Salmon testes) was solubilized in a bio-deep eutectic solvent [(bio-DES), obtained by the complexation of choline chloride and ethylene glycol at 1:2 molar ratio] containing 1% w/w of silver chloride (AgCl) to yield a AgCl decorated DNA based hybrid material. Concentration dependent formation of AgCl crystals in the DES was observed and upon interaction with DNA it gave formation of a cephalopod shaped hybrid material. DNA was found to maintain its chemical and structural stability in the material. Further, AgCl microstructures were found to have orderly self assembled on the DNA helices indicating the electrostatic interaction between Ag(+) and phosphate side chain of DNA as a driving force for the formation of the material with ordered microstructural distribution of AgCl. Furthermore, the functionalized material exhibited excellent antibacterial and bactericidal activity against both Gram negative and Gram positive pathogenic bacteria. Copyright © 2015 Elsevier B.V. All rights reserved.

On the nature of a glassy state of matter in a hydrated protein: Relation to protein function.

PubMed

Teeter, M M; Yamano, A; Stec, B; Mohanty, U

2001-09-25

Diverse biochemical and biophysical experiments indicate that all proteins, regardless of size or origin, undergo a dynamic transition near 200 K. The cause of this shift in dynamic behavior, termed a "glass transition," and its relation to protein function are important open questions. One explanation postulated for the transition is solidification of correlated motions in proteins below the transition. We verified this conjecture by showing that crambin's radius of gyration (Rg) remains constant below approximately 180 K. We show that both atom position and dynamics of protein and solvent are physically coupled, leading to a novel cooperative state. This glassy state is identified by negative slopes of the Debye-Waller (B) factor vs. temperature. It is composed of multisubstate side chains and solvent. Based on generalization of Adam-Gibbs' notion of a cooperatively rearranging region and decrease of the total entropy with temperature, we calculate the slope of the Debye-Waller factor. The results are in accord with experiment.

A coarse-grained model of the effective interaction for charged amino acid residues and its application to formation of GCN4-pLI tetramer

NASA Astrophysics Data System (ADS)

Kawaguchi, Kazutomo; Nakagawa, Satoshi; Kurniawan, Isman; Kodama, Koichi; Arwansyah, Muhammad Saleh; Nagao, Hidemi

2018-03-01

We present a simple coarse-grained model of the effective interaction for charged amino acid residues, such as Glu and Lys, in a water solvent. The free-energy profile as a function of the distance between two charged amino acid side-chain analogues in an explicit water solvent is calculated with all-atom molecular dynamics simulation and thermodynamic integration method. The calculated free-energy profile is applied to the coarse-grained potential of the effective interaction between two amino acid residues. The Langevin dynamics simulations with our coarse-grained potential are performed for association of a small protein complex, GCN4-pLI tetramer. The tetramer conformation reproduced by our coarse-grained model is similar to the X-ray crystallographic structure. We show that the effective interaction between charged amino acid residues stabilises association and orientation of protein complex. We also investigate the association pathways of GCN4-pLI tetramer.

Enhancing Electrophoretic Display Lifetime: Thiol-Polybutadiene Evaporation Barrier Property Response to Network Microstructure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, Caitlyn Christian

An evaporation barrier is required to enhance the lifetime of electrophoretic deposition (EPD) displays. As EPD functions on the basis of reversible deposition and resuspension of colloids suspended in a solvent, evaporation of the solvent ultimately leads to device failure. Incorporation of a thiol-polybutadiene elastomer into EPD displays enabled display lifetime surpassing six months in counting and catalyzed rigid display transition into a flexible package. Final flexible display transition to mass production compels an electronic-ink approach to encapsulate display suspension within an elastomer shell. Final thiol-polybutadiene photosensitive resin network microstructure was idealized to be dense, homogeneous, and expose an elasticmore » response to deformation. Research at hand details an approach to understanding microstructural change within display elastomers. Polybutadiene-based resin properties are modified via polymer chain structure, with and without added aromatic urethane methacrylate difunctionality, and in measuring network response to variation in thiol and initiator concentration. Dynamic mechanical analysis results signify that cross-linked segments within a difunctionalized polybutadiene network were on average eight times more elastically active than that of linked segments within a non-functionalized polybutadiene network. Difunctionalized polybutadiene samples also showed a 2.5 times greater maximum elastic modulus than non-functionalized samples. Hybrid polymer composed of both polybutadiene chains encompassed TE-2000 stiffness and B-1000 elasticity for use in encapsulating display suspension. Later experiments measured kinetic and rheological response due to alteration in dithiol cross-linker chain length via real time Fourier transform infrared spectroscopy and real-time dynamic rheology. Distinct differences were discovered between dithiol resin systems, as maximum thiol conversion achieved in short and long chain length dithiols was 86% and 11%, respectively. Oscillatory real-time rheological experiments confirmed a more uniform network to better dissipate applied shear in short chain length dithiol systems, as long chain length dithiols relayed a steep internal stress build-up due to less cross-links and chain entanglements. Thorough understanding of network formation aids the production of a stronger and impermeable elastomeric barrier for preservation of EPD displays.« less

Mutational And Structural Studies Of The PixD BLUF Output Signal That Affects Light-Regulated Interactions With PixE

PubMed Central

Yuan, Hua; Dragnea, Vladimira; Wu, Qiong; Gardner, Kevin H.; Bauer, Carl E.

2011-01-01

PixD (Slr1694) is a BLUF (blue-light using FAD) photoreceptor used by the cyanobacterium Synechocystis sp. PCC6803 to control phototaxis toward blue light. In this study we probe the involvement of a conserved Tyr8-Gln50-Met93 triad in promoting an output signal upon blue light excitation of the bound flavin. Analysis of acrylamide quenching of Trp91 fluorescence shows that the side chain of this residue remains partially solvent exposed in both the lit and dark states. Mutational analysis demonstrates that substitution mutations at Tyr8 and Gln50 result in the loss of the photocycle while a mutation of Met93 does not appreciably disturb the formation of the light excited state and only minimally accelerates its decay from 5.7 s to 4.5 s. However, mutations in Tyr8, Gln50 and Met93 disrupt the ability of PixD dimers to interact with PixE to form a higher ordered PixD10-PixE5 complex, which is indicative of a lit conformational state. Solution NMR spectroscopy and X-ray crystallographic analyses confirm that a Tyr8 to Phe mutation is locked in a pseudo light excited state revealing flexible areas in PixD that likely constitute part of an output signal upon light excitation of wild type PixD. PMID:21688827

Covalent docking of selected boron-based serine beta-lactamase inhibitors

NASA Astrophysics Data System (ADS)

Sgrignani, Jacopo; Novati, Beatrice; Colombo, Giorgio; Grazioso, Giovanni

2015-05-01

AmpC β-lactamase is a hydrolytic enzyme conferring resistance to β-lactam antibiotics in multiple Gram-negative bacteria. Therefore, identification of non-β-lactam compounds able to inhibit the enzyme is crucial for the development of novel antibacterial therapies. In general, AmpC inhibitors have to engage the highly solvent-exposed catalytic site of the enzyme. Therefore, understanding the implications of ligand-protein induced-fit and water-mediated interactions behind the inhibitor-enzyme recognition process is fundamental for undertaking structure-based drug design process. Here, we focus on boronic acids, a promising class of beta-lactamase covalent inhibitors. First, we optimized a docking protocol able to reproduce the experimentally determined binding mode of AmpC inhibitors bearing a boronic group. This goal was pursued (1) performing rigid and flexible docking calculations aiming to establish the role of the side chain conformations; and (2) investigating the role of specific water molecules in shaping the enzyme active site and mediating ligand protein interactions. Our calculations showed that some water molecules, conserved in the majority of the considered X-ray structures, are needed to correctly predict the binding pose of known covalent AmpC inhibitors. On this basis, we formalized our findings in a docking and scoring protocol that could be useful for the structure-based design of new boronic acid AmpC inhibitors.

Phenylalanine-427 of anthrax protective antigen functions in both pore formation and protein translocation.

PubMed

Sun, Jianjun; Lang, Alexander E; Aktories, Klaus; Collier, R John

2008-03-18

The protective antigen (PA) moiety of anthrax toxin forms a heptameric pore in endosomal membranes of mammalian cells and translocates the enzymatic moieties of the toxin to the cytosol of these cells. Phenylalanine-427 (F427), a solvent-exposed residue in the lumen of the pore, was identified earlier as being crucial for the transport function of PA. The seven F427 residues were shown in electrophysiological studies to form a clamp that catalyzes protein translocation through the pore. Here, we demonstrate by a variety of tests that certain F427 mutations also profoundly inhibit the conformational transition of the heptameric PA prepore to the pore and thereby block pore formation in membranes. Lysine, arginine, aspartic acid, or glycine at position 427 strongly inhibited this acidic pH-induced conformational transition, whereas histidine, serine, and threonine had virtually no effect on this step, but inhibited translocation instead. Thus, it is possible to inhibit pore formation or translocation selectively, depending on the choice of the side chain at position 427; and the net inhibition of the PA transport function by any given F427 mutation is the product of its effects on both steps. Mutations inhibiting either or both steps elicited a strong dominant-negative phenotype. These findings demonstrate the dual functions of F427 and underline its central role in transporting the enzymatic moieties of anthrax toxin across membranes.

Structural prediction of a novel chitinase from the psychrophilic Glaciozyma antarctica PI12 and an analysis of its structural properties and function

NASA Astrophysics Data System (ADS)

Ramli, Aizi Nor Mazila; Mahadi, Nor Muhammad; Shamsir, Mohd Shahir; Rabu, Amir; Joyce-Tan, Kwee Hong; Murad, Abdul Munir Abdul; Illias, Rosli Md.

2012-08-01

The structure of psychrophilic chitinase (CHI II) from Glaciozyma antarctica PI12 has yet to be studied in detail. Due to its low sequence identity (<30 %), the structural prediction of CHI II is a challenge. A 3D model of CHI II was built by first using a threading approach to search for a suitable template and to generate an optimum target-template alignment, followed by model building using MODELLER9v7. Analysis of the catalytic insertion domain structure in CHI II revealed an increase in the number of aromatic residues and longer loops compared to mesophilic and thermophilic chitinases. A molecular dynamics simulation was used to examine the stability of the CHI II structure at 273, 288 and 300 K. Structural analysis of the substrate-binding cleft revealed a few exposed aromatic residues. Substitutions of certain amino acids in the surface and loop regions of CHI II conferred an increased flexibility to the enzyme, allowing for an adaptation to cold temperatures. A substrate binding comparison of CHI II with the mesophilic chitinase from Coccidioides immitis, 1D2K, suggested that the psychrophilic adaptation and catalytic activity at low temperatures were achieved through a reduction in the number of salt bridges, fewer hydrogen bonds and an increase in the exposure of the hydrophobic side chains to the solvent.

SCit: web tools for protein side chain conformation analysis.

PubMed

Gautier, R; Camproux, A-C; Tufféry, P

2004-07-01

SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each protein for side chain positioning and the identification of side chains with unlikely conformations. The SCit web server is accessible at http://bioserv.rpbs.jussieu.fr/SCit.

Molecular weight dependent structure and charge transport in MAPLE-deposited poly(3-hexylthiophene) thin films

DOE PAGES

Dong, Ban Xuan; Smith, Mitchell; Strzalka, Joseph; ...

2018-02-06

In this work, poly(3-hexylthiophene) (P3HT) films prepared using the matrix-assisted pulsed laser evaporation (MAPLE) technique are shown to possess morphological structures that are dependent on molecular weight (MW). Specifically, the structures of low MW samples of MAPLE-deposited film are composed of crystallites/aggregates embedded within highly disordered environments, whereas those of high MW samples are composed of aggregated domains connected by long polymer chains. Additionally, the crystallite size along the side-chain (100) direction decreases, whereas the conjugation length increases with increasing molecular weight. This is qualitatively similar to the structure of spin-cast films, though the MAPLE-deposited films are more disordered. In-planemore » carrier mobilities in the MAPLE-deposited samples increase with MW, consistent with the notion that longer chains bridge adjacent aggregated domains thereby facilitating more effective charge transport. The carrier mobilities in the MAPLE-deposited simples are consistently lower than those in the solvent-cast samples for all molecular weights, consistent with the shorter conjugation length in samples prepared by this deposition technique.« less

Molecular weight dependent structure and charge transport in MAPLE-deposited poly(3-hexylthiophene) thin films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Ban Xuan; Smith, Mitchell; Strzalka, Joseph

In this work, poly(3-hexylthiophene) (P3HT) films prepared using the matrix-assisted pulsed laser evaporation (MAPLE) technique are shown to possess morphological structures that are dependent on molecular weight (MW). Specifically, the structures of low MW samples of MAPLE-deposited film are composed of crystallites/aggregates embedded within highly disordered environments, whereas those of high MW samples are composed of aggregated domains connected by long polymer chains. Additionally, the crystallite size along the side-chain (100) direction decreases, whereas the conjugation length increases with increasing molecular weight. This is qualitatively similar to the structure of spin-cast films, though the MAPLE-deposited films are more disordered. In-planemore » carrier mobilities in the MAPLE-deposited samples increase with MW, consistent with the notion that longer chains bridge adjacent aggregated domains thereby facilitating more effective charge transport. The carrier mobilities in the MAPLE-deposited simples are consistently lower than those in the solvent-cast samples for all molecular weights, consistent with the shorter conjugation length in samples prepared by this deposition technique.« less

Extraction, scrub, and strip test results for the salt waste processing facility caustic side solvent extraction solvent example

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters, T. B.

An Extraction, Scrub, and Strip (ESS) test was performed on a sample of Salt Waste Processing Facility (SWPF) Caustic-Side Solvent Extraction (CSSX) solvent and salt simulant to determine cesium distribution ratios (D(Cs)), and cesium concentration in the strip effluent (SE) and decontaminated salt solution (DSS) streams; this data will be used by Parsons to help determine if the solvent is qualified for use at the SWPF. The ESS test showed acceptable performance of the solvent for extraction, scrub, and strip operations. The extraction D(Cs) measured 12.9, exceeding the required value of 8. This value is consistent with results from previousmore » ESS tests using similar solvent formulations. Similarly, scrub and strip cesium distribution ratios fell within acceptable ranges.« less

DNA-Templated Polymerization of Side-Chain-Functionalized Peptide Nucleic Acid Aldehydes

PubMed Central

Kleiner, Ralph E.; Brudno, Yevgeny; Birnbaum, Michael E.; Liu, David R.

2009-01-01

The DNA-templated polymerization of synthetic building blocks provides a potential route to the laboratory evolution of sequence-defined polymers with structures and properties not necessarily limited to those of natural biopolymers. We previously reported the efficient and sequence-specific DNA-templated polymerization of peptide nucleic acid (PNA) aldehydes. Here, we report the enzyme-free, DNA-templated polymerization of side-chain-functionalized PNA tetramer and pentamer aldehydes. We observed that the polymerization of tetramer and pentamer PNA building blocks with a single lysine-based side chain at various positions in the building block could proceed efficiently and sequence-specifically. In addition, DNA-templated polymerization also proceeded efficiently and in a sequence-specific manner with pentamer PNA aldehydes containing two or three lysine side chains in a single building block to generate more densely functionalized polymers. To further our understanding of side-chain compatibility and expand the capabilities of this system, we also examined the polymerization efficiencies of 20 pentamer building blocks each containing one of five different side-chain groups and four different side-chain regio- and stereochemistries. Polymerization reactions were efficient for all five different side-chain groups and for three of the four combinations of side-chain regio- and stereochemistries. Differences in the efficiency and initial rate of polymerization correlate with the apparent melting temperature of each building block, which is dependent on side-chain regio- and stereochemistry, but relatively insensitive to side-chain structure among the substrates tested. Our findings represent a significant step towards the evolution of sequence-defined synthetic polymers and also demonstrate that enzyme-free nucleic acid-templated polymerization can occur efficiently using substrates with a wide range of side-chain structures, functionalization positions within each building block, and functionalization densities. PMID:18341334

Organization of pectic arabinan and galactan side chains in association with cellulose microfibrils in primary cell walls and related models envisaged.

PubMed

Zykwinska, Agata; Thibault, Jean-François; Ralet, Marie-Christine

2007-01-01

The structure of arabinan and galactan domains in association with cellulose microfibrils was investigated using enzymatic and alkali degradation procedures. Sugar beet and potato cell wall residues (called 'natural' composites), rich in pectic neutral sugar side chains and cellulose, as well as 'artificial' composites, created by in vitro adsorption of arabinan and galactan side chains onto primary cell wall cellulose, were studied. These composites were sequentially treated with enzymes specific for pectic side chains and hot alkali. The degradation approach used showed that most of the arabinan and galactan side chains are in strong interaction with cellulose and are not hydrolysed by pectic side chain-degrading enzymes. It seems unlikely that isolated arabinan and galactan chains are able to tether adjacent microfibrils. However, cellulose microfibrils may be tethered by different pectic side chains belonging to the same pectic macromolecule.

Residue-Specific Side-Chain Polymorphisms via Particle Belief Propagation.

PubMed

Ghoraie, Laleh Soltan; Burkowski, Forbes; Li, Shuai Cheng; Zhu, Mu

2014-01-01

Protein side chains populate diverse conformational ensembles in crystals. Despite much evidence that there is widespread conformational polymorphism in protein side chains, most of the X-ray crystallography data are modeled by single conformations in the Protein Data Bank. The ability to extract or to predict these conformational polymorphisms is of crucial importance, as it facilitates deeper understanding of protein dynamics and functionality. In this paper, we describe a computational strategy capable of predicting side-chain polymorphisms. Our approach extends a particular class of algorithms for side-chain prediction by modeling the side-chain dihedral angles more appropriately as continuous rather than discrete variables. Employing a new inferential technique known as particle belief propagation, we predict residue-specific distributions that encode information about side-chain polymorphisms. Our predicted polymorphisms are in relatively close agreement with results from a state-of-the-art approach based on X-ray crystallography data, which characterizes the conformational polymorphisms of side chains using electron density information, and has successfully discovered previously unmodeled conformations.

Side-chain mobility in the folded state of Myoglobin

NASA Astrophysics Data System (ADS)

Lammert, Heiko; Onuchic, Jose

We study the accessibility of alternative side-chain rotamer configurations in the native state of Myoglobin, using an all-atom structure-based model. From long, unbiased simulation trajectories we determine occupancies of rotameric states and also estimate configurational and vibrational entropies. Direct sampling of the full native-state dynamics, enabled by the simple model, reveals facilitation of side-chain motions by backbone dynamics. Correlations between different dihedral angles are quantified and prove to be weak. We confirm global trends in the mobilities of side-chains, following burial and also the chemical character of residues. Surface residues loose little configurational entropy upon folding; side-chains contribute significantly to the entropy of the folded state. Mobilities of buried side-chains vary strongly with temperature. At ambient temperature, individual side-chains in the core of the protein gain substantial access to alternative rotamers, with occupancies that are likely observable experimentally. Finally, the dynamics of buried side-chains may be linked to the internal pockets, available to ligand gas molecules in Myoglobin.

Residues with similar hexagon neighborhoods share similar side-chain conformations.

PubMed

Li, Shuai Cheng; Bu, Dongbo; Li, Ming

2012-01-01

We present in this study a new approach to code protein side-chain conformations into hexagon substructures. Classical side-chain packing methods consist of two steps: first, side-chain conformations, known as rotamers, are extracted from known protein structures as candidates for each residue; second, a searching method along with an energy function is used to resolve conflicts among residues and to optimize the combinations of side chain conformations for all residues. These methods benefit from the fact that the number of possible side-chain conformations is limited, and the rotamer candidates are readily extracted; however, these methods also suffer from the inaccuracy of energy functions. Inspired by threading and Ab Initio approaches to protein structure prediction, we propose to use hexagon substructures to implicitly capture subtle issues of energy functions. Our initial results indicate that even without guidance from an energy function, hexagon structures alone can capture side-chain conformations at an accuracy of 83.8 percent, higher than 82.6 percent by the state-of-art side-chain packing methods.

Investigation of the interfacial reaction between metal and fluorine-contained polyimides

NASA Astrophysics Data System (ADS)

Yang, Ching-Yu; Chen, J. S.; Hsu, S. L. C.

2005-07-01

In this work, thin metal films (Cr and Ta) were deposited on fluorine-contained polyimides, 6FDA-BisAAF, and 6FDA-PPD. The chemical states of the metal/polyimide samples were characterized by using x-ray photoelectron spectroscopy (XPS). XPS analysis reveals that metal-C, C-O, and metal-O bondings are present in metallized 6FDA-BisAAF and 6FDA-PPD. C-F bonds are observed in bare 6FDA-BisAAF and 6FDA-PPD however, they are not seen in the metallized samples. Disappearance of the C-F bonding is attributed to the disruption of CF3 side groups from the main chains of 6FDA-BisAAF and 6FDA-PPD when the chains are exposed to the plasma during the metal deposition. Nevertheless, the disruption of CF3 side groups also creates sites for the formation of metal-C or C-O bondings, which provide a positive adhesion strength at the metal/polyimide interface, as revealed by the tape test.

Amino acids at water-vapor interfaces: surface activity and orientational ordering.

PubMed

Vöhringer-Martinez, Esteban; Toro-Labbé, Alejandro

2010-10-14

The surface activity and orientational ordering of amino acids at water-vapor interfaces were studied with molecular dynamics simulations in combination with thermodynamic integration and umbrella sampling. Asparagine, representing amino acids with polar side chains, displays no surface activity. Tryptophan, in contrast, with its hydrophobic indole ring as side chain unveils a free energy minimum at the water-vapor interface, which lies 6 kJ/mol under the hydration free energy. To study the orientational ordering of tryptophan along the interface, the order parameter was calculated. At the free energy minimum and at the Gibbs dividing surface, the order parameter reveals a parallel alignment of the indole ring with the water surface exposing the π-system to electrophiles in the hydrophobic phase and indicating polarization dependent spectroscopy. In the vicinity of this position a perpendicular orientation is obtained. The surface excess, calculated from the potential of mean force along the interface, is in excellent agreement with experimental measurements.

SCit: web tools for protein side chain conformation analysis

PubMed Central

Gautier, R.; Camproux, A.-C.; Tufféry, P.

2004-01-01

SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each protein for side chain positioning and the identification of side chains with unlikely conformations. The SCit web server is accessible at http://bioserv.rpbs.jussieu.fr/SCit. PMID:15215438

Simulation study of the initial crystallization processes of poly(3-hexylthiophene) in solution: ordering dynamics of main chains and side chains.

PubMed

Takizawa, Yuumi; Shimomura, Takeshi; Miura, Toshiaki

2013-05-23

We study the initial nucleation dynamics of poly(3-hexylthiophene) (P3HT) in solution, focusing on the relationship between the ordering process of main chains and that of side chains. We carried out Langevin dynamics simulation and found that the initial nucleation processes consist of three steps: the ordering of ring orientation, the ordering of main-chain vectors, and the ordering of side chains. At the start, the normal vectors of thiophene rings aligned in a very short time, followed by alignment of main-chain end-to-end vectors. The flexible side-chain ordering took almost 5 times longer than the rigid-main-chain ordering. The simulation results indicated that the ordering of side chains was induced after the formation of the regular stack structure of main chains. This slow ordering dynamics of flexible side chains is one of the factors that cause anisotropic nuclei growth, which would be closely related to the formation of nanofiber structures without external flow field. Our simulation results revealed how the combined structure of the planar and rigid-main-chain backbones and the sparse flexible side chains lead to specific ordering behaviors that are not observed in ordinary linear polymer crystallization processes.

Regulation of substituent groups on morphologies and self-assembly of organogels based on some azobenzene imide derivatives

NASA Astrophysics Data System (ADS)

Jiao, Tifeng; Wang, Yujin; Zhang, Qingrui; Zhou, Jingxin; Gao, Faming

2013-04-01

In this paper, new azobenzene imide derivatives with different substituent groups were designed and synthesized. Their gelation behaviors in 21 solvents were tested as novel low-molecular-mass organic gelators. It was shown that the alkyl substituent chains and headgroups of azobenzene residues in gelators played a crucial role in the gelation behavior of all compounds in various organic solvents. More alkyl chains in molecular skeletons in present gelators are favorable for the gelation of organic solvents. Scanning electron microscopy and atomic force microscopy observations revealed that the gelator molecules self-assemble into different aggregates, from wrinkle, lamella, and belt to fiber with the change of solvents. Spectral studies indicated that there existed different H-bond formations between amide groups and conformations of methyl chains. The present work may give some insight to the design and character of new organogelators and soft materials with special molecular structures.

Regulation of substituent groups on morphologies and self-assembly of organogels based on some azobenzene imide derivatives

PubMed Central

2013-01-01

In this paper, new azobenzene imide derivatives with different substituent groups were designed and synthesized. Their gelation behaviors in 21 solvents were tested as novel low-molecular-mass organic gelators. It was shown that the alkyl substituent chains and headgroups of azobenzene residues in gelators played a crucial role in the gelation behavior of all compounds in various organic solvents. More alkyl chains in molecular skeletons in present gelators are favorable for the gelation of organic solvents. Scanning electron microscopy and atomic force microscopy observations revealed that the gelator molecules self-assemble into different aggregates, from wrinkle, lamella, and belt to fiber with the change of solvents. Spectral studies indicated that there existed different H-bond formations between amide groups and conformations of methyl chains. The present work may give some insight to the design and character of new organogelators and soft materials with special molecular structures. PMID:23566628

Steric interactions determine side-chain conformations in protein cores.

PubMed

Caballero, D; Virrueta, A; O'Hern, C S; Regan, L

2016-09-01

We investigate the role of steric interactions in defining side-chain conformations in protein cores. Previously, we explored the strengths and limitations of hard-sphere dipeptide models in defining sterically allowed side-chain conformations and recapitulating key features of the side-chain dihedral angle distributions observed in high-resolution protein structures. Here, we show that modeling residues in the context of a particular protein environment, with both intra- and inter-residue steric interactions, is sufficient to specify which of the allowed side-chain conformations is adopted. This model predicts 97% of the side-chain conformations of Leu, Ile, Val, Phe, Tyr, Trp and Thr core residues to within 20°. Although the hard-sphere dipeptide model predicts the observed side-chain dihedral angle distributions for both Thr and Ser, the model including the protein environment predicts side-chain conformations to within 20° for only 60% of core Ser residues. Thus, this approach can identify the amino acids for which hard-sphere interactions alone are sufficient and those for which additional interactions are necessary to accurately predict side-chain conformations in protein cores. We also show that our approach can predict alternate side-chain conformations of core residues, which are supported by the observed electron density. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Sophorolipid-induced dimpling and increased porosity in solvent-cast short-chain polyhydroxyalkanoate films: impact on thermo-mechanical properties

USDA-ARS?s Scientific Manuscript database

Sophorolipids (SL; microbial glycolipids) were used as additives in solvent-cast short-chain polyhydroxyalkanoate (sc-PHA) films to enhance surface roughness and porosity. Poly-3-hydroxybutyrate (PHB), poly-(6%)-3-hydroxybutyrate-co-(94%)-3-hydroxyvalerate (PHB/V), and poly-(90%)-3-hydroxybutyrate-c...

Effects of alkyl chain length and solvents on thermodynamic dissociation constants of the ionic liquids with one carboxyl group in the alkyl chain of imidazolium cations.

PubMed

Chen, Yuehua; Wang, Huiyong; Wang, Jianji

2014-05-01

Thermodynamic dissociation constants of the Brønsted acidic ionic liquids (ILs) are important for their catalytic and separation applications. In this work, a series of imidazolium bromides with one carboxylic acid substitute group in their alkyl chain ([{(CH2)nCOOH}mim]Br, n = 1,3,5,7) have been synthesized, and their dissociation constants (pKa) at different ionic strengths have been determined in aqueous and aqueous organic solvents at 0.1 mole fraction (x) of ethanol, glycol, iso-propanol, and dimethyl sulfoxide by potentiometric titrations at 298.2 K. The standard thermodynamic dissociation constants (pKa(T)) of the ILs in these solvents were calculated from the extended Debye-Hückel equation. It was found that the pKa values increased with the increase of ionic strength of the media and of the addition of organic solvent in water. The pKa(T) values also increased with the increase of the alkyl chain length of cations of the ILs. In addition, the effect of solvent nature on pKa(T) values is interpreted from solvation of the dissociation components and their Gibbs energy of transfer from water to aqueous organic solutions.

Kerr effect in the isotropic phase of a side-chain polymeric liquid crystal

NASA Astrophysics Data System (ADS)

Reys, V.; Dormoy, Y.; Collin, D.; Keller, P.; Martinoty, P.

1992-02-01

The birefringence induced by a pulsed electrical field was used to study the pretransitional effects associated with the isotropic phase of a side-chain polysiloxane. The results obtained show that these effects are characterised by a conventional value of the static exponent and an abnormal value of the dynamic exponent, which shows that the dynamic theory of low molecular weight liquid crystals does not apply. The results also reveal competition between the dipolar moments induced by the electrical field and the permanent moments of the mesogenic molecules. La biréfringence induite par un champ électrique impulsionnel a été utilisée pour étudier les effets prétransitionnels associés à la phase isotrope d'un polysiloxane à chaînes latérales. Les résultats obtenus montrent que ces effets sont caractérisés par une valeur classique de l'exposant statique et une valeur anormale de l'exposant dynamique. Ce dernier résultat montre que la théorie dynamique des cristaux liquides de bas poids moléculaire n'est pas applicable au cas présent. Les expériences mettent également en évidence une compétition entre les moments dipolaires induits par le champ électrique et les moments permanents des molécules mésogènes.

Conformation transitions of a single polyelectrolyte chain in a poor solvent: a replica-exchange lattice Monte-Carlo study.

PubMed

Wang, Lang; Wang, Zheng; Jiang, Run; Yin, Yuhua; Li, Baohui

2017-03-15

The thermodynamic behaviors of a strongly charged polyelectrolyte chain in a poor solvent are studied using replica-exchange Monte-Carlo simulations on a lattice model, focusing on the effects of finite chain length and the solvent quality on the chain conformation and conformation transitions. The neutralizing counterions and solvent molecules are considered explicitly. The thermodynamic quantities that vary continuously with temperature over a wide range are computed using the multiple histogram reweighting method. Our results suggest that the strength of the short-range hydrophobic interaction, the chain length, and the temperature of the system, characterized by ε, N, and T, respectively, are important parameters that control the conformations of a charged chain. When ε is moderate, the competition between the electrostatic energy and the short-range hydrophobic interaction leads to rich conformations and conformation transitions for a longer chain with a fixed length. Our results have unambiguously demonstrated the stability of the n-pearl-necklace structures, where n has a maximum value and decreases with decreasing temperature. The maximum n value increases with increasing chain length. Our results have also demonstrated the first-order nature of the conformation transitions between the m-pearl and the (m-1)-pearl necklaces. With the increase of ε, the transition temperature increases and the first-order feature becomes more pronounced. It is deduced that at the thermodynamic limit of infinitely long chain length, the conformational transitions between the m-pearl and the (m-1)-pearl necklaces may remain first order when ε > 0 and m = 2 or 3. Pearl-necklace conformations cannot be observed when either ε is too large or N is too small. To observe a pearl-necklace conformation, the T value needs to be carefully chosen for simulations performed at only a single temperature.

Transitions of tethered chain molecules under tension.

PubMed

Luettmer-Strathmann, Jutta; Binder, Kurt

2014-09-21

An applied tension force changes the equilibrium conformations of a polymer chain tethered to a planar substrate and thus affects the adsorption transition as well as the coil-globule and crystallization transitions. Conversely, solvent quality and surface attraction are reflected in equilibrium force-extension curves that can be measured in experiments. To investigate these effects theoretically, we study tethered chains under tension with Wang-Landau simulations of a bond-fluctuation lattice model. Applying our model to pulling experiments on biological molecules we obtain a good description of experimental data in the intermediate force range, where universal features dominate and finite size effects are small. For tethered chains in poor solvent, we observe the predicted two-phase coexistence at transitions from the globule to stretched conformations and also discover direct transitions from crystalline to stretched conformations. A phase portrait for finite chains constructed by evaluating the density of states for a broad range of solvent conditions and tensions shows how increasing tension leads to a disappearance of the globular phase. For chains in good solvents tethered to hard and attractive surfaces we find the predicted scaling with the chain length in the low-force regime and show that our results are well described by an analytical, independent-bond approximation for the bond-fluctuation model for the highest tensions. Finally, for a hard or slightly attractive surface the stretching of a tethered chain is a conformational change that does not correspond to a phase transition. However, when the surface attraction is sufficient to adsorb a chain it will undergo a desorption transition at a critical value of the applied force. Our results for force-induced desorption show the transition to be discontinuous with partially desorbed conformations in the coexistence region.

Characterization of Hydrophobic Interactions of Polymers with Water and Phospholipid Membranes Using Molecular Dynamics Simulations

NASA Astrophysics Data System (ADS)

Drenscko, Mihaela

Polymers and lipid membranes are both essential soft materials. The structure and hydrophobicity/hydrophilicity of polymers, as well as the solvent they are embedded in, ultimately determines their size and shape. Understating the variation of shape of the polymer as well as its interactions with model biological membranes can assist in understanding the biocompatibility of the polymer itself. Computer simulations, in particular molecular dynamics, can aid in characterization of the interaction of polymers with solvent, as well as polymers with model membranes. In this thesis, molecular dynamics serve to describe polymer interactions with a solvent (water) and with a lipid membrane. To begin with, we characterize the hydrophobic collapse of single polystyrene chains in water using molecular dynamics simulations. Specifically, we calculate the potential of mean force for the collapse of a single polystyrene chain in water using metadynamics, comparing the results between all atomistic with coarse-grained molecular simulation. We next explore the scaling behavior of the collapsed globular shape at the minimum energy configuration, characterized by the radius of gyration, as a function of chain length. The exponent is close to one third, consistent with that predicted for a polymer chain in bad solvent. We also explore the scaling behavior of the Solvent Accessible Surface Area (SASA) as a function of chain length, finding a similar exponent for both all-atomistic and coarse-grained simulations. Furthermore, calculation of the local water density as a function of chain length near the minimum energy configuration suggests that intermediate chain lengths are more likely to form dewetted states, as compared to shorter or longer chain lengths. Next, in order to investigate the molecular interactions between single hydrophobic polymer chains and lipids in biological membranes and at lipid membrane/solvent interface, we perform a series of molecular dynamics simulations of small membranes using all atomistic and coarse-grained methods. The molecular interaction between common polymer chains used in biomedical applications and the cell membrane is unknown. This interaction may affect the biocompatibility of the polymer chains. Molecular dynamics simulations offer an emerging tool to characterize the interaction between common degradable polymer chains used in biomedical applications, such as polycaprolactone, and model cell membranes. We systematically characterize with long-time all-atomistic molecular dynamics simulations the interaction between single polycaprolactone chains of varying chain lengths with a model phospholipid membrane. We find that the length of polymer chain greatly affects the nature of interaction with the membrane, as well as the membrane properties. Furthermore, we next utilize advanced sampling techniques in molecular dynamics to characterize the two-dimensional free energy surface for the interaction of varying polymer chain lengths (short, intermediate, and long) with model cell membranes. We find that the free energy minimum shifts from the membrane-water interface to the hydrophobic core of the phospholipid membrane as a function of chain length. These results can be used to design polymer chain lengths and chemistries to optimize their interaction with cell membranes at the molecular level.

Protein-Backbone Thermodynamics across the Membrane Interface.

PubMed

Bereau, Tristan; Kremer, Kurt

2016-07-07

The thermodynamics of insertion of a protein in a membrane depends on the fine interplay between backbone and side-chain contributions interacting with the lipid environment. Using computer simulations, we probe how different descriptions of the backbone glycyl unit affect the thermodynamics of insertion of individual residues, dipeptides, and entire transmembrane helices. Due to the lack of reference data, we first introduce an efficient methodology to estimate atomistic potential of mean force (PMF) curves from a series of representative and uncorrelated coarse-grained (CG) snapshots. We find strong discrepancies between two CG models, Martini and PLUM, against reference atomistic PMFs and experiments. Atomistic simulations suggest a weak free energy of insertion between water and a POPC membrane for the glycyl unit, in overall agreement with experimental results despite severe assumptions in our calculations. We show that refining the backbone contribution in PLUM significantly improves the PMF of insertion of the WALP16 transmembrane peptide. An improper balance between the glycyl backbone and the attached side chain will lead to energetic artifacts, rationalizing Martini's overstabilization of WALP's adsorbed interfacial state. It illustrates difficulties associated with free-energy-based parametrizations of single-residue models, as the relevant free energy of partitioning used for force-field parametrization does not arise from the entire residue but rather the solvent-accessible chemical groups.

Valence structures of aromatic bioactive compounds: a combined theoretical and experimental study.

PubMed

Wickrama Arachchilage, Anoja Pushpamali; Feyer, Vitaliy; Plekan, Oksana; Iakhnenko, Marianna; Prince, Kevin C; Wang, Feng

2012-09-01

Valence electronic structures of three recently isolated aryl bioactive compounds, namely 2-phenylethanol (2PE), p-hydroxyphenylethanol (HPE) and 4-hydroxybenzaldehyde (HBA), are studied using a combined theoretical and experimental method. Density functional theory-based calculations indicate that the side chains cause electron charge redistribution and therefore influence the aromaticity of the benzene derivatives. The simulated IR spectra further reveal features induced by the side chains. Solvent effects on the IR spectra are simulated using the polarizable continuum model, which exhibits enhancement of the O-H stretch vibrations with significant red-shift of 464 cm(-1) in 2PE. A significant spectral peak splitting of 94 cm(-1) between O(4)-H and O(8)-H of HPE is revealed in an aqueous environment. Experimental measurements for valence binding energy spectra for 2PE, HPE and HBA are presented and analyzed using outer-valence Green function calculations. The experimental (predicted) first ionization energies are measured as 9.19 (8.79), 8.47 (8.27) and 8.97 (8.82) eV for 2PE, HPE and HBA, respectively. The frontier orbitals (highest occupied molecular orbitals, HOMOs, and lowest unoccupied molecular orbitals, LUMOs) have similar atomic orbital characters although the HOMO-LUMO energy gaps are quite different.

Supramolecular Phase-Selective Gelation by Peptides Bearing Side-Chain Azobenzenes: Effect of Ultrasound and Potential for Dye Removal and Oil Spill Remediation

PubMed Central

Bachl, Jürgen; Oehm, Stefan; Mayr, Judith; Cativiela, Carlos; Marrero-Tellado, José Juan; Díaz Díaz, David

2015-01-01

Phase selective gelation (PSG) of organic phases from their non-miscible mixtures with water was achieved using tetrapeptides bearing a side-chain azobenzene moiety. The presence of the chromophore allowed PSG at the same concentration as the minimum gelation concentration (MGC) necessary to obtain the gels in pure organic phases. Remarkably, the presence of the water phase during PSG did not impact the thermal, mechanical, and morphological properties of the corresponding organogels. In the case of miscible oil/water mixtures, the entire mixture was gelled, resulting in the formation of quasi-hydrogels. Importantly, PSG could be triggered at room temperature by ultrasound treatment of the mixture or by adding ultrasound-aided concentrated solution of the peptide in an oil-phase to a mixture of the same oil and water. Moreover, the PSG was not affected by the presence of salts or impurities existing in water from natural sources. The process could be scaled-up, and the oil phases (e.g., aromatic solvents, gasoline, diesel fuel) recovered almost quantitatively after a simple distillation process, which also allowed the recovery and reuse of the gelator. Finally, these peptidic gelators could be used to quantitatively remove toxic dyes from aqueous solutions. PMID:26006247

New statistical potential for quality assessment of protein models and a survey of energy functions

PubMed Central

2010-01-01

Background Scoring functions, such as molecular mechanic forcefields and statistical potentials are fundamentally important tools in protein structure modeling and quality assessment. Results The performances of a number of publicly available scoring functions are compared with a statistical rigor, with an emphasis on knowledge-based potentials. We explored the effect on accuracy of alternative choices for representing interaction center types and other features of scoring functions, such as using information on solvent accessibility, on torsion angles, accounting for secondary structure preferences and side chain orientation. Partially based on the observations made, we present a novel residue based statistical potential, which employs a shuffled reference state definition and takes into account the mutual orientation of residue side chains. Atom- and residue-level statistical potentials and Linux executables to calculate the energy of a given protein proposed in this work can be downloaded from http://www.fiserlab.org/potentials. Conclusions Among the most influential terms we observed a critical role of a proper reference state definition and the benefits of including information about the microenvironment of interaction centers. Molecular mechanical potentials were also tested and found to be over-sensitive to small local imperfections in a structure, requiring unfeasible long energy relaxation before energy scores started to correlate with model quality. PMID:20226048

Structure-Energy Relationships of Halogen Bonds in Proteins.

PubMed

Scholfield, Matthew R; Ford, Melissa Coates; Carlsson, Anna-Carin C; Butta, Hawera; Mehl, Ryan A; Ho, P Shing

2017-06-06

The structures and stabilities of proteins are defined by a series of weak noncovalent electrostatic, van der Waals, and hydrogen bond (HB) interactions. In this study, we have designed and engineered halogen bonds (XBs) site-specifically to study their structure-energy relationship in a model protein, T4 lysozyme. The evidence for XBs is the displacement of the aromatic side chain toward an oxygen acceptor, at distances that are equal to or less than the sums of their respective van der Waals radii, when the hydroxyl substituent of the wild-type tyrosine is replaced by a halogen. In addition, thermal melting studies show that the iodine XB rescues the stabilization energy from an otherwise destabilizing substitution (at an equivalent noninteracting site), indicating that the interaction is also present in solution. Quantum chemical calculations show that the XB complements an HB at this site and that solvent structure must also be considered in trying to design molecular interactions such as XBs into biological systems. A bromine substitution also shows displacement of the side chain, but the distances and geometries do not indicate formation of an XB. Thus, we have dissected the contributions from various noncovalent interactions of halogens introduced into proteins, to drive the application of XBs, particularly in biomolecular design.

Role of F357 as an Oxygen Gate in the Oxidative Half-Reaction of Choline Oxidase.

PubMed

Salvi, Francesca; Rodriguez, Isela; Hamelberg, Donald; Gadda, Giovanni

2016-03-15

Choline oxidase from Arthrobacter globiformis catalyzes the oxidation of choline to glycine betaine by using oxygen as an electron acceptor. A partially rate limiting isomerization of the reduced wild-type enzyme during the reaction with oxygen was previously detected using solvent viscosity effects. In this study, we hypothesized that the side chains of M62 and F357, located at the entrance to the active site of choline oxidase, may be related to the slow isomerization detected. We engineered a double-variant enzyme M62A/F357A. The kinetic characterization of the double-variant enzyme showed a lack of the isomerization detected in wild-type choline oxidase, and a lack of saturation with an oxygen concentration as high as 1 mM, while most other kinetic parameters were similar to those of wild-type choline oxidase. The kinetic characterization of the single-variant enzymes established that only the side chain of F357 plays a role in the isomerization of choline oxidase in the oxidative half-reaction. Molecular dynamics studies suggest that the slow isomerization related to F357 is possibly due to the participation of the phenyl ring in a newly proposed gating mechanism for a narrow tunnel, assumed to regulate the access of oxygen to the reduced cofactor.

Tunable, mixed-resolution modeling using library-based Monte Carlo and graphics processing units

PubMed Central

Mamonov, Artem B.; Lettieri, Steven; Ding, Ying; Sarver, Jessica L.; Palli, Rohith; Cunningham, Timothy F.; Saxena, Sunil; Zuckerman, Daniel M.

2012-01-01

Building on our recently introduced library-based Monte Carlo (LBMC) approach, we describe a flexible protocol for mixed coarse-grained (CG)/all-atom (AA) simulation of proteins and ligands. In the present implementation of LBMC, protein side chain configurations are pre-calculated and stored in libraries, while bonded interactions along the backbone are treated explicitly. Because the AA side chain coordinates are maintained at minimal run-time cost, arbitrary sites and interaction terms can be turned on to create mixed-resolution models. For example, an AA region of interest such as a binding site can be coupled to a CG model for the rest of the protein. We have additionally developed a hybrid implementation of the generalized Born/surface area (GBSA) implicit solvent model suitable for mixed-resolution models, which in turn was ported to a graphics processing unit (GPU) for faster calculation. The new software was applied to study two systems: (i) the behavior of spin labels on the B1 domain of protein G (GB1) and (ii) docking of randomly initialized estradiol configurations to the ligand binding domain of the estrogen receptor (ERα). The performance of the GPU version of the code was also benchmarked in a number of additional systems. PMID:23162384

Thermosensitive mPEG-b-PA-g-PNIPAM comb block copolymer micelles: effect of hydrophilic chain length and camptothecin release behavior.

PubMed

Yang, Xiao-Li; Luo, Yan-Ling; Xu, Feng; Chen, Ya-Shao

2014-02-01

Block copolymer micelles are extensively used as drug controlled release carriers, showing promising application prospects. The comb or brush copolymers are especially of great interest, whose densely-grafted side chains may be important for tuning the physicochemical properties and conformation in selective solvents, even in vitro drug release. The purpose of this work was to synthesize novel block copolymer combs via atom transfer radical polymerization, to evaluate its physicochemical features in solution, to improve drug release behavior and to enhance the bioavailablity, and to decrease cytotoxicity. The physicochemical properties of the copolymer micelles were examined by modulating the composition and the molecular weights of the building blocks. A dialysis method was used to load hydrophobic camptothecin (CPT), and the CPT release and stability were detected by UV-vis spectroscopy and high-performance liquid chromatography, and the cytotoxicity was evaluated by MTT assays. The copolymers could self-assemble into well-defined spherical core-shell micelle aggregates in aqueous solution, and showed thermo-induced micellization behavior, and the critical micelle concentration was 2.96-27.64 mg L(-1). The micelles were narrow-size-distribution, with hydrodynamic diameters about 128-193 nm, depending on the chain length of methoxy polyethylene glycol (mPEG) blocks and poly(N-isopropylacrylamide) (PNIPAM) graft chains or/and compositional ratios of mPEG to PNIPAM. The copolymer micelles could stably and effectively load CPT but avoid toxicity and side-effects, and exhibited thermo-dependent controlled and targeted drug release behavior. The copolymer micelles were safe, stable and effective, and could potentially be employed as CPT controlled release carriers.

Switching effect of the side chain on quantum walks on triple graphs

NASA Astrophysics Data System (ADS)

Du, Yi-Mu; Lu, Li-Hua; Li, You-Quan

2015-07-01

We consider a continuous-time quantum walk on a triple graph and investigate the influence of the side chain on propagation in the main chain. Calculating the interchange of the probabilities between the two parts of the main chain, we find that a switching effect appears if there is an odd number of points in the side chain when concrete conditions between the length of the main chain and the position of the side chain are satisfied. However, such an effect does not occur if there is an even number of points in the side chain. We also suggest two proposals for experiments to demonstrate this effect, which may be employed to design a new type of switching device.

Conformational analysis of glutamic acid: a density functional approach using implicit continuum solvent model.

PubMed

Turan, Başak; Selçuki, Cenk

2014-09-01

Amino acids are constituents of proteins and enzymes which take part almost in all metabolic reactions. Glutamic acid, with an ability to form a negatively charged side chain, plays a major role in intra and intermolecular interactions of proteins, peptides, and enzymes. An exhaustive conformational analysis has been performed for all eight possible forms at B3LYP/cc-pVTZ level. All possible neutral, zwitterionic, protonated, and deprotonated forms of glutamic acid structures have been investigated in solution by using polarizable continuum model mimicking water as the solvent. Nine families based on the dihedral angles have been classified for eight glutamic acid forms. The electrostatic effects included in the solvent model usually stabilize the charged forms more. However, the stability of the zwitterionic form has been underestimated due to the lack of hydrogen bonding between the solute and solvent; therefore, it is observed that compact neutral glutamic acid structures are more stable in solution than they are in vacuum. Our calculations have shown that among all eight possible forms, some are not stable in solution and are immediately converted to other more stable forms. Comparison of isoelectronic glutamic acid forms indicated that one of the structures among possible zwitterionic and anionic forms may dominate over the other possible forms. Additional investigations using explicit solvent models are necessary to determine the stability of charged forms of glutamic acid in solution as our results clearly indicate that hydrogen bonding and its type have a major role in the structure and energy of conformers.

Protein Side-Chain Resonance Assignment and NOE Assignment Using RDC-Defined Backbones without TOCSY Data3

PubMed Central

Zeng, Jianyang; Zhou, Pei; Donald, Bruce Randall

2011-01-01

One bottleneck in NMR structure determination lies in the laborious and time-consuming process of side-chain resonance and NOE assignments. Compared to the well-studied backbone resonance assignment problem, automated side-chain resonance and NOE assignments are relatively less explored. Most NOE assignment algorithms require nearly complete side-chain resonance assignments from a series of through-bond experiments such as HCCH-TOCSY or HCCCONH. Unfortunately, these TOCSY experiments perform poorly on large proteins. To overcome this deficiency, we present a novel algorithm, called NASCA (NOE Assignment and Side-Chain Assignment), to automate both side-chain resonance and NOE assignments and to perform high-resolution protein structure determination in the absence of any explicit through-bond experiment to facilitate side-chain resonance assignment, such as HCCH-TOCSY. After casting the assignment problem into a Markov Random Field (MRF), NASCA extends and applies combinatorial protein design algorithms to compute optimal assignments that best interpret the NMR data. The MRF captures the contact map information of the protein derived from NOESY spectra, exploits the backbone structural information determined by RDCs, and considers all possible side-chain rotamers. The complexity of the combinatorial search is reduced by using a dead-end elimination (DEE) algorithm, which prunes side-chain resonance assignments that are provably not part of the optimal solution. Then an A* search algorithm is employed to find a set of optimal side-chain resonance assignments that best fit the NMR data. These side-chain resonance assignments are then used to resolve the NOE assignment ambiguity and compute high-resolution protein structures. Tests on five proteins show that NASCA assigns resonances for more than 90% of side-chain protons, and achieves about 80% correct assignments. The final structures computed using the NOE distance restraints assigned by NASCA have backbone RMSD 0.8 – 1.5 Å from the reference structures determined by traditional NMR approaches. PMID:21706248

IMAAAGINE: a webserver for searching hypothetical 3D amino acid side chain arrangements in the Protein Data Bank

PubMed Central

Nadzirin, Nurul; Willett, Peter; Artymiuk, Peter J.; Firdaus-Raih, Mohd

2013-01-01

We describe a server that allows the interrogation of the Protein Data Bank for hypothetical 3D side chain patterns that are not limited to known patterns from existing 3D structures. A minimal side chain description allows a variety of side chain orientations to exist within the pattern, and generic side chain types such as acid, base and hydroxyl-containing can be additionally deployed in the search query. Moreover, only a subset of distances between the side chains need be specified. We illustrate these capabilities in case studies involving arginine stacks, serine-acid group arrangements and multiple catalytic triad-like configurations. The IMAAAGINE server can be accessed at http://mfrlab.org/grafss/imaaagine/. PMID:23716645

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs.

PubMed

Sachs, B; Al Masaoudi, T; Merk, H F; Erdmann, S

2004-10-01

Amino-penicillins are a major cause of delayed-type reactions to penicillins. The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.

Enhanced picture of protein-folding intermediates using organic solvents in H/D exchange and quench-flow experiments

PubMed Central

Nishimura, Chiaki; Dyson, H. Jane; Wright, Peter E.

2005-01-01

Hydrogen/deuterium exchange followed by trapping of the labeled species in the aprotic solvent DMSO has been used to elucidate structure in both the burst-phase molten globule-folding intermediate of apomyoglobin and in an equilibrium intermediate that models the kinetic intermediate. Precise estimates can be made of exchange times in an interrupted exchange-out experiment at pH 4 followed by analysis in DMSO solution, giving extensive sequence-specific information about the structure of the equilibrium intermediate. In addition, the use of DMSO as a solvent for NMR measurements after quench-flow pH-pulse labeling experiments gives a greatly increased data set for the elucidation of the kinetic folding pathway. Interestingly, differences are observed in some regions of apomyoglobin between the equilibrium and kinetic intermediates. These differences are quantitative rather than qualitative; that is, the overall patterns of labeling and secondary structure formation remain similar between the two species. However, local differences are observed, which probably reflect the difference in the solution conditions for the equilibrium experiment (pH 4) vs. the kinetic experiment (pH 6) and the change in the status of the stabilizing hydrogen bond between the side chains of His-24 and His-119. PMID:15769860

Fluorine-Rich Planetary Environments as Possible Habitats for Life

PubMed Central

Budisa, Nediljko; Kubyshkin, Vladimir; Schulze-Makuch, Dirk

2014-01-01

In polar aprotic organic solvents, fluorine might be an element of choice for life that uses selected fluorinated building blocks as monomers of choice for self-assembling of its catalytic polymers. Organofluorine compounds are extremely rare in the chemistry of life as we know it. Biomolecules, when fluorinated such as peptides or proteins, exhibit a “fluorous effect”, i.e., they are fluorophilic (neither hydrophilic nor lipophilic). Such polymers, capable of creating self-sorting assemblies, resist denaturation by organic solvents by exclusion of fluorocarbon side chains from the organic phase. Fluorous cores consist of a compact interior, which is shielded from the surrounding solvent. Thus, we can anticipate that fluorine-containing “teflon”-like or “non-sticking” building blocks might be monomers of choice for the synthesis of organized polymeric structures in fluorine-rich planetary environments. Although no fluorine-rich planetary environment is known, theoretical considerations might help us to define chemistries that might support life in such environments. For example, one scenario is that all molecular oxygen may be used up by oxidation reactions on a planetary surface and fluorine gas could be released from F-rich magma later in the history of a planetary body to result in a fluorine-rich planetary environment. PMID:25370378

Automated side-chain model building and sequence assignment by template matching.

PubMed

Terwilliger, Thomas C

2003-01-01

An algorithm is described for automated building of side chains in an electron-density map once a main-chain model is built and for alignment of the protein sequence to the map. The procedure is based on a comparison of electron density at the expected side-chain positions with electron-density templates. The templates are constructed from average amino-acid side-chain densities in 574 refined protein structures. For each contiguous segment of main chain, a matrix with entries corresponding to an estimate of the probability that each of the 20 amino acids is located at each position of the main-chain model is obtained. The probability that this segment corresponds to each possible alignment with the sequence of the protein is estimated using a Bayesian approach and high-confidence matches are kept. Once side-chain identities are determined, the most probable rotamer for each side chain is built into the model. The automated procedure has been implemented in the RESOLVE software. Combined with automated main-chain model building, the procedure produces a preliminary model suitable for refinement and extension by an experienced crystallographer.

Structure of Chlorobium tepidum sepiapterin reductase complex reveals the novel substrate binding mode for stereospecific production of L-threo-tetrahydrobiopterin.

PubMed

Supangat, Supangat; Seo, Kyung Hye; Choi, Yong Kee; Park, Young Shik; Son, Daeyoung; Han, Chang-deok; Lee, Kon Ho

2006-01-27

Sepiapterin reductase (SR) is involved in the last step of tetrahydrobiopterin (BH(4)) biosynthesis by reducing the di-keto group of 6-pyruvoyl tetrahydropterin. Chlorobium tepidum SR (cSR) generates a distinct BH(4) product, L-threo-BH(4) (6R-(1'S,2'S)-5,6,7,8-BH(4)), whereas animal enzymes produce L-erythro-BH(4) (6R-(1'R,2'S)-5,6,7,8-BH(4)) although it has high amino acid sequence similarities to the other animal enzymes. To elucidate the structural basis for the different reaction stereospecificities, we have determined the three-dimensional structures of cSR alone and complexed with NADP and sepiapterin at 2.1 and 1.7 A resolution, respectively. The overall folding of the cSR, the binding site for the cofactor NADP(H), and the positions of active site residues were quite similar to the mouse and the human SR. However, significant differences were found in the substrate binding region of the cSR. In comparison to the mouse SR complex, the sepiapterin in the cSR is rotated about 180 degrees around the active site and bound between two aromatic side chains of Trp-196 and Phe-99 so that its pterin ring is shifted to the opposite side, but its side chain position is not changed. The swiveled sepiapterin binding results in the conversion of the side chain configuration, exposing the opposite face for hydride transfer from NADPH. The different sepiapterin binding mode within the conserved catalytic architecture presents a novel strategy of switching the reaction stereospecificities in the same protein fold.

Product ion tandem mass spectrometric differentiation of regioisomeric side-chain groups in cathinone derivatives.

PubMed

Abiedalla, Younis; DeRuiter, Jack; Clark, C Randall

2016-07-30

Precursor materials are available to prepare aminoketone drugs containing regioisomeric propyl and isopropyl side-chain groups related to the drug alpha-pyrrovalerone (Flakka) and MDPV (3,4-methylenedioxypyrrovalerone). These compounds yield equivalent regioisomeric iminium cation base peaks in electron ionization mass spectrometry (EI-MS). The propyl and isopropyl side-chain groups related to alpha-pyrrovalerone and MDPV were prepared and evaluated in EI-MS and tandem mass spectrometry (MS/MS) product ion experiments. Deuterium labeling in both the pyrrolidine and alkyl side-chain groups allowed for the confirmation of the structures for the major product ions formed from the regioisomeric EI-MS iminium cation base peaks. These iminium cation base peaks show characteristic product ion spectra which allow differentiation of the side-chain propyl and isopropyl groups in the structure. The n-propyl side chain containing iminium cation base peak (m/z 126) in the EI-MS spectrum yields a major product ion at m/z 84 while the regioisomeric m/z 126 base peak for the isopropyl side chain yields a characteristic product ion at m/z 70. Deuterium labeling in both the pyrrolidine ring and the alkyl side chain confirmed the process for the formation of these major product ions. Product ion fragmentation provides useful data for differentiation of n-propyl and isopropyl side-chain iminium cations from cathinone derivative drugs of abuse. Regioisomeric n-propyl and isopropyl iminium cations of equal mass yield characteristic product ions identifying the alkyl side-chain regioisomers in the pyrrolidine cathinone derivatives. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Protein-ligand docking with multiple flexible side chains

NASA Astrophysics Data System (ADS)

Zhao, Yong; Sanner, Michel F.

2008-09-01

In this work, we validate and analyze the results of previously published cross docking experiments and classify failed dockings based on the conformational changes observed in the receptors. We show that a majority of failed experiments (i.e. 25 out of 33, involving four different receptors: cAPK, CDK2, Ricin and HIVp) are due to conformational changes in side chains near the active site. For these cases, we identify the side chains to be made flexible during docking calculation by superimposing receptors and analyzing steric overlap between various ligands and receptor side chains. We demonstrate that allowing these side chains to assume rotameric conformations enables the successful cross docking of 19 complexes (ligand all atom RMSD < 2.0 Å) using our docking software FLIPDock. The number of side receptor side chains interacting with a ligand can vary according to the ligand's size and shape. Hence, when starting from a complex with a particular ligand one might have to extend the region of potential interacting side chains beyond the ones interacting with the known ligand. We discuss distance-based methods for selecting additional side chains in the neighborhood of the known active site. We show that while using the molecular surface to grow the neighborhood is more efficient than Euclidian-distance selection, the number of side chains selected by these methods often remains too large and additional methods for reducing their count are needed. Despite these difficulties, using geometric constraints obtained from the network of bonded and non-bonded interactions to rank residues and allowing the top ranked side chains to be flexible during docking makes 22 out of 25 complexes successful.

Asymmetric Alkyl Side-Chain Engineering of Naphthalene Diimide-Based n-Type Polymers for Efficient All-Polymer Solar Cells.

PubMed

Jia, Tao; Li, Zhenye; Ying, Lei; Jia, Jianchao; Fan, Baobing; Zhong, Wenkai; Pan, Feilong; He, Penghui; Chen, Junwu; Huang, Fei; Cao, Yong

2018-02-13

The design and synthesis of three n-type conjugated polymers based on a naphthalene diimide-thiophene skeleton are presented. The control polymer, PNDI-2HD, has two identical 2-hexyldecyl side chains, and the other polymers have different alkyl side chains; PNDI-EHDT has a 2-ethylhexyl and a 2-decyltetradecyl side chain, and PNDI-BOOD has a 2-butyloctyl and a 2-octyldodecyl side chain. These copolymers with different alkyl side chains exhibit higher melting and crystallization temperatures, and stronger aggregation in solution, than the control copolymer PNDI-2HD that has the same side chain. Polymer solar cells based on the electron-donating copolymer PTB7-Th and these novel copolymers exhibit nearly the same open-circuit voltage of 0.77 V. Devices based on the copolymer PNDI-BOOD with different side chains have a power-conversion efficiency of up to 6.89%, which is much higher than the 4.30% obtained with the symmetric PNDI-2HD. This improvement can be attributed to the improved charge-carrier mobility and the formation of favorable film morphology. These observations suggest that the molecular design strategy of incorporating different side chains can provide a new and promising approach to developing n-type conjugated polymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simple Physics-Based Analytical Formulas for the Potentials of Mean Force of the Interaction of Amino Acid Side Chains in Water. VII. Charged-Hydrophobic/Polar and Polar-Hydrophobic/Polar Side Chains.

PubMed

Makowski, Mariusz; Liwo, Adam; Scheraga, Harold A

2017-01-19

The physics-based potentials of side-chain-side-chain interactions corresponding to pairs composed of charged and polar, polar and polar, charged and hydrophobic, and hydrophobic and hydrophobic side chains have been determined. A total of 144 four-dimensional potentials of mean force (PMFs) of all possible pairs of molecules modeling these pairs were determined by umbrella-sampling molecular dynamics simulations in explicit water as functions of distance and orientation, and the analytical expressions were then fitted to the PMFs. Depending on the type of interacting sites, the analytical approximation to the PMF is a sum of terms corresponding to van der Waals interactions and cavity-creation involving the nonpolar sections of the side chains and van der Waals, cavity-creation, and electrostatic (charge-dipole or dipole-dipole) interaction energies and polarization energies involving the charged or polar sections of the side chains. The model used in this work reproduces all features of the interacting pairs. The UNited RESidue force field with the new side-chain-side-chain interaction potentials was preliminarily tested with the N-terminal part of the B-domain of staphylococcal protein A (PDBL 1BDD ; a three-α-helix bundle) and UPF0291 protein YnzC from Bacillus subtilis (PDB: 2HEP ; an α-helical hairpin).

C-peptide inhibitors of Ebola virus glycoprotein-mediated cell entry: effects of conjugation to cholesterol and side chain-side chain crosslinking.

PubMed

Higgins, Chelsea D; Koellhoffer, Jayne F; Chandran, Kartik; Lai, Jonathan R

2013-10-01

We previously described potent inhibition of Ebola virus entry by a 'C-peptide' based on the GP2 C-heptad repeat region (CHR) targeted to endosomes ('Tat-Ebo'). Here, we report the synthesis and evaluation of C-peptides conjugated to cholesterol, and Tat-Ebo analogs containing covalent side chain-side chain crosslinks to promote α-helical conformation. We found that the cholesterol-conjugated C-peptides were potent inhibitors of Ebola virus glycoprotein (GP)-mediated cell entry (~10(3)-fold reduction in infection at 40 μM). However, this mechanism of inhibition is somewhat non-specific because the cholesterol-conjugated peptides also inhibited cell entry mediated by vesicular stomatitis virus glycoprotein G. One side chain-side chain crosslinked peptide had moderately higher activity than the parent compound Tat-Ebo. Circular dichroism revealed that the cholesterol-conjugated peptides unexpectedly formed a strong α-helical conformation that was independent of concentration. Side chain-side chain crosslinking enhanced α-helical stability of the Tat-Ebo variants, but only at neutral pH. These result provide insight into mechanisms of C-peptide inhibiton of Ebola virus GP-mediated cell entry. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of Alkylthio and Alkoxy Side Chains in Polymer Donor Materials for Organic Solar Cells.

PubMed

Cui, Chaohua; Wong, Wai-Yeung

2016-02-01

Side chains play a considerable role not only in improving the solubility of polymers for solution-processed device fabrication, but also in affecting the molecular packing, electron affinity and thus the device performance. In particular, electron-donating side chains show unique properties when employed to tune the electronic character of conjugated polymers in many cases. Therefore, rational electron-donating side chain engineering can improve the photovoltaic properties of the resulting polymer donors to some extent. Here, a survey of some representative examples which use electron-donating alkylthio and alkoxy side chains in conjugated organic polymers for polymer solar cell applications will be presented. It is envisioned that an analysis of the effect of such electron-donating side chains in polymer donors would contribute to a better understanding of this kind of side chain behavior in solution-processed conjugated organic polymers for polymer solar cells. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

"There is a chain of connections": using syndemics theory to understand HIV treatment side effects.

PubMed

Gagnon, Marilou

2018-03-12

Side effects are central to the experience of living longer with HIV but rarely have they been studied alone. Unlike other aspects of that experience, like quality of life, treatment adherence, chronicity, episodic disability, aging, health, and viral load suppression, side effects have not benefited from the same level of empirical and theoretical engagement from qualitative researchers. In this paper, we draw on syndemics theory and 50 qualitative interviews to better understand the experience of HIV treatment side effects. Two main categories were identified in the data: side effects as a product and side effects as a risk factor. The first category suggests that side effects are not just the product of taking antiretroviral drugs. They are also the product of particular conditions and tend to cluster with other health problems. The second category puts forward the idea that side effects can act as a syndemic risk factor by exposing PLWH to a greater risk of developing health problems and creating conditions in which psychosocial issues are more likely to emerge. The paper concludes by calling for more research on the complex nature of side effects and for the development of comprehensive approaches for the assessment and management of side effects.

Theoretical study of solvent effects on the coil-globule transition

NASA Astrophysics Data System (ADS)

Polson, James M.; Opps, Sheldon B.; Abou Risk, Nicholas

2009-06-01

The coil-globule transition of a polymer in a solvent has been studied using Monte Carlo simulations of a single chain subject to intramolecular interactions as well as a solvent-mediated effective potential. This solvation potential was calculated using several different theoretical approaches for two simple polymer/solvent models, each employing hard-sphere chains and hard-sphere solvent particles as well as attractive square-well potentials between some interaction sites. For each model, collapse is driven by variation in a parameter which changes the energy mismatch between monomers and solvent particles. The solvation potentials were calculated using two fundamentally different methodologies, each designed to predict the conformational behavior of polymers in solution: (1) the polymer reference interaction site model (PRISM) theory and (2) a many-body solvation potential (MBSP) based on scaled particle theory introduced by Grayce [J. Chem. Phys. 106, 5171 (1997)]. For the PRISM calculations, two well-studied solvation monomer-monomer pair potentials were employed, each distinguished by the closure relation used in its derivation: (i) a hypernetted-chain (HNC)-type potential and (ii) a Percus-Yevick (PY)-type potential. The theoretical predictions were each compared to results obtained from explicit-solvent discontinuous molecular dynamics simulations on the same polymer/solvent model systems [J. Chem. Phys. 125, 194904 (2006)]. In each case, the variation in the coil-globule transition properties with solvent density is mostly qualitatively correct, though the quantitative agreement between the theory and prediction is typically poor. The HNC-type potential yields results that are more qualitatively consistent with simulation. The conformational behavior of the polymer upon collapse predicted by the MBSP approach is quantitatively correct for low and moderate solvent densities but is increasingly less accurate for higher densities. At high solvent densities, the PRISM-HNC and MBSP approaches tend to overestimate, while the PRISM-PY approach underestimates the tendency of the solvent to drive polymer collapse.

Electric Dipole Transition Moments and Solvent-Dependent Interactions of Fluorescent Boron-Nitrogen Substituted Indole Derivatives.

PubMed

Saif, Mari; Widom, Julia R; Xu, Senmiao; Abbey, Eric R; Liu, Shih-Yuan; Marcus, Andrew H

2015-06-25

Fluorescent analogues of the indole side chain of tryptophan can be useful spectroscopic probes of protein-protein and protein-DNA interactions. Here we present linear dichroism and solvent-dependent spectroscopic studies of two fluorescent analogues of indole, in which the organic C═C unit is substituted with the isosteric inorganic B-N unit. We studied the so-called "external" BN indole, which has C2v symmetry, and the "fused" BN indole with Cs symmetry. We performed a combination of absorption and fluorescence spectroscopy, ultraviolet linear dichroism (UV-LD) in stretched poly(ethylene) (PE) films, and quantum chemical calculations on both BN indole compounds. Our measurements allowed us to characterize the degree of alignment for both molecules in stretched PE films. We thus determined the orientations and magnitudes of the two lowest energy electric dipole transition moments (EDTMs) for external BN indole, and the two lowest energy EDTMs for fused BN indole within the 30 000-45 000 cm(-1) spectral range. We compared our experimental results to those of quantum chemical calculations using standard density functional theory (DFT). Our theoretical predictions for the low-energy EDTMs are in good agreement with our experimental data. The absorption and fluorescence spectra of the external and the fused BN indoles are sensitive to solvent polarity. Our results indicate that the fused BN indole experiences much greater solvation interactions with polar solvents than does the external BN indole.

Amino Acid Side Chain Interactions in the Presence of Salts

PubMed Central

Hassan, Sergio A.

2005-01-01

The effects of salt on the intermolecular interactions between polar/charged amino acids are investigated through molecular dynamics simulations. The mean forces and associated potentials are calculated for NaCl salt in the 0–2 M concentration range at 298 K. It is found that the addition of salt may stabilize or destabilize the interactions, depending on the nature of the interacting molecules. The degree of (de)stabilization is quantified, and the origin of the salt-dependent modulation is discussed based upon an analysis of solvent density profiles. To gain insight into the molecular origin of the salt modulation, spatial distribution functions (sdf’s) are calculated, revealing a high degree of solvent structuredness in all cases. The peaks in the sdf’s are consistent with long-range hydrogen-bonding networks connecting the solute hydrophilic groups, and that contribute to their intermolecular solvent-induced forces. The restructuring of water around the solutes as they dissociate from close contact is analyzed. This analysis offers clues on how the solvent structure modulates the effective intermolecular interactions in complex solutes. This modulation results from a critical balance between bulk electrostatic forces and those exerted by (i) the water molecules in the structured region between the monomers, which is disrupted by ions that transiently enter the hydration shells, and (ii) the ions in the hydration shells in direct interactions with the solutes. The implications of these findings in protein/ligand (noncovalent) association/dissociation mechanisms are briefly discussed. PMID:16479276

Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard

PubMed Central

Terwilliger, Thomas C.; Grosse-Kunstleve, Ralf W.; Afonine, Pavel V.; Moriarty, Nigel W.; Zwart, Peter H.; Hung, Li-Wei; Read, Randy J.; Adams, Paul D.

2008-01-01

The PHENIX AutoBuild wizard is a highly automated tool for iterative model building, structure refinement and density modification using RESOLVE model building, RESOLVE statistical density modification and phenix.refine structure refinement. Recent advances in the AutoBuild wizard and phenix.refine include automated detection and application of NCS from models as they are built, extensive model-completion algorithms and automated solvent-molecule picking. Model-completion algorithms in the AutoBuild wizard include loop building, crossovers between chains in different models of a structure and side-chain optimization. The AutoBuild wizard has been applied to a set of 48 structures at resolutions ranging from 1.1 to 3.2 Å, resulting in a mean R factor of 0.24 and a mean free R factor of 0.29. The R factor of the final model is dependent on the quality of the starting electron density and is relatively independent of resolution. PMID:18094468

Atomistic Simulations of Hydrodynamic and Interaction Forces on Functionalized Silica Nanoparticles

NASA Astrophysics Data System (ADS)

Lane, J. Matthew D.; Ismail, Ahmed E.; Chandross, Michael; Lorenz, Christian D.; Grest, Gary S.

2009-03-01

It is often desired to prevent the flocculation and phase separation of nanoparticles in solution. This can be accomplished either by manipulating the solvent or by tailoring the surface chemistry of the nanoparticles through functionalization with a monolayer of oligomer chains. Since it is not known how these functionalized coatings affect the interactions between nanoparticles and with the surrounding solvent, we present results from a series of molecular dynamics simulations of polyethylene oxide (PEO) coated silica nanoparticles of varying size (5 to 20 nm diameter) in water. For a single nanoparticle we determined the Stokes drag on the nanoparticle as it moves through the solvent and as it approaches a wall. Due to hydrodynamic interactions there are large finite size effects which we estimate by varying the size of the simulation cell. We also determined both solvent-mediated (velocity-independent) and lubrication (velocity-dependent) forces between two nanoparticles as a function of the coverage and chain length of the PEO chains.

Orotidine 5'-Monophosphate Decarboxylase: Probing the Limits of the Possible for Enzyme Catalysis.

PubMed

Richard, John P; Amyes, Tina L; Reyes, Archie C

2018-04-17

The mystery associated with catalysis by what were once regarded as protein black boxes, diminished with the X-ray crystallographic determination of the three-dimensional structures of enzyme-substrate complexes. The report that several high-resolution X-ray crystal structures of orotidine 5'-monophosphate decarboxylase (OMPDC) failed to provide a consensus mechanism for enzyme-catalyzed decarboxylation of OMP to form uridine 5'-monophosphate, therefore, provoked a flurry of controversy. This controversy was fueled by the enormous 10 23 -fold rate acceleration for this enzyme, which had " jolted many biochemists' assumptions about the catalytic potential of enzymes." Our studies on the mechanism of action of OMPDC provide strong evidence that catalysis by this enzyme is not fundamentally different from less proficient catalysts, while highlighting important architectural elements that enable a peak level of performance. Many enzymes undergo substrate-induced protein conformational changes that trap their substrates in solvent occluded protein cages, but the conformational change induced by ligand binding to OMPDC is incredibly complex, as required to enable the development of 22 kcal/mol of stabilizing binding interactions with the phosphodianion and ribosyl substrate fragments of OMP. The binding energy from these fragments is utilized to activate OMPDC for catalysis of decarboxylation at the orotate fragment of OMP, through the creation of a tight, catalytically active, protein cage from the floppy, open, unliganded form of OMPDC. Such utilization of binding energy for ligand-driven conformational changes provides a general mechanism to obtain specificity in transition state binding. The rate enhancement that results from the binding of carbon acid substrates to enzymes is partly due to a reduction in the carbon acid p K a that is associated with ligand binding. The binding of UMP to OMPDC results in an unusually large >12 unit decrease in the p K a = 29 for abstraction of the C-6 substrate hydrogen, due to stabilization of an enzyme-bound vinyl carbanion, which is also an intermediate of OMPDC-catalyzed decarboxylation. The protein-ligand interactions operate to stabilize the vinyl carbanion at the enzyme active site compared to aqueous solution, rather than to stabilize the transition state for the concerted electrophilic displacement of CO 2 by H + that avoids formation of this reaction intermediate. There is evidence that OMPDC induces strain into the bound substrate. The interaction between the amide side chain of Gln-215 from the phosphodianion gripper loop and the hydroxymethylene side chain of Ser-154 from the pyrimidine umbrella of ScOMPDC position the amide side chain to interact with the phosphodianion of OMP. There are no direct stabilizing interactions between dianion gripper protein side chains Gln-215, Tyr-217, and Arg-235 and the pyrimidine ring at the decarboxylation transition state. Rather these side chains function solely to hold OMPDC in the catalytically active closed conformation. The hydrophobic side chains that line the active site of OMPDC in the region of the departing CO 2 product may function to stabilize the decarboxylation transition state by providing hydrophobic solvation of this product.

Olfactory function in painters exposed to organic solvents.

PubMed

Sandmark, B; Broms, I; Löfgren, L; Ohlson, C G

1989-02-01

The olfactory receptor cells are in direct contact with the exterior environment, and some chemical agents can impair olfactory function. The olfactory function of 54 painters exposed to organic solvents was compared with that of 42 unexposed referents. A new clinical test validated for the sense of smell was used, the University of Pennsylvania Smell Identification Test. Age, smoking habits, exposure to organic solvents, and medical disorders of importance for the sense of smell were recorded. The painters had a somewhat lower test score than the referents. However, the influence of the exposure variable was not statistically significant in a multiple regression analysis including age and smoking habits. The exposure to organic solvents was low, and therefore an effect of high exposure on olfactory function cannot be ruled out. Since some of the painters had earlier been highly exposed, the effects of high exposure are likely to be reversible.

Unique Aspects of the Structure and Dynamics of Elementary Iβ Cellulose Microfibrils Revealed by Computational Simulations1[OPEN

PubMed Central

Oehme, Daniel P.; Downton, Matthew T.; Doblin, Monika S.; Wagner, John; Gidley, Michael J.; Bacic, Antony

2015-01-01

The question of how many chains an elementary cellulose microfibril contains is critical to understanding the molecular mechanism(s) of cellulose biosynthesis and regulation. Given the hexagonal nature of the cellulose synthase rosette, it is assumed that the number of chains must be a multiple of six. We present molecular dynamics simulations on three different models of Iβ cellulose microfibrils, 18, 24, and 36 chains, to investigate their structure and dynamics in a hydrated environment. The 36-chain model stays in a conformational space that is very similar to the initial crystalline phase, while the 18- and 24-chain models sample a conformational space different from the crystalline structure yet similar to conformations observed in recent high-temperature molecular dynamics simulations. Major differences in the conformations sampled between the different models result from changes to the tilt of chains in different layers, specifically a second stage of tilt, increased rotation about the O2-C2 dihedral, and a greater sampling of non-TG exocyclic conformations, particularly the GG conformation in center layers and GT conformation in solvent-exposed exocyclic groups. With a reinterpretation of nuclear magnetic resonance data, specifically for contributions made to the C6 peak, data from the simulations suggest that the 18- and 24-chain structures are more viable models for an elementary cellulose microfibril, which also correlates with recent scattering and diffraction experimental data. These data inform biochemical and molecular studies that must explain how a six-particle cellulose synthase complex rosette synthesizes microfibrils likely comprised of either 18 or 24 chains. PMID:25786828

Tuning Surface Properties of Poly(methyl methacrylate) Film Using Poly(perfluoromethyl methacrylate)s with Short Perfluorinated Side Chains.

PubMed

Sohn, Eun-Ho; Ha, Jong-Wook; Lee, Soo-Bok; Park, In Jun

2016-09-27

To control the surface properties of a commonly used polymer, poly(methyl methacrylate) (PMMA), poly(perfluoromethyl methacrylate)s (PFMMAs) with short perfluorinated side groups (i.e., -CF3, -CF2CF3, -(CF3)2, -CF2CF2CF3) were used as blend components because of their good solubility in organic solvents, low surface energies, and high optical transmittance. The surface energies of the blend films of PFMMA with the -CF3 group and PMMA increased continuously with increasing PMMA contents from 17.6 to 26.0 mN/m, whereas those of the other polymer blend films remained at very low levels (10.2-12.6 mN/m), similar to those of pure PFMMAs, even when the blends contained 90 wt %PMMA. Surface morphology and composition measurements revealed that this result originated from the different blend structures, such as lateral and vertical phase separations. We expect that these PFMMAs will be useful in widening the applicable window of PMMA.

Hidden regularity and universal classification of fast side chain motions in proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rajeshwar, Rajitha; Smith, Jeremy C.; Krishnam, Marimuthu

Proteins display characteristic dynamical signatures that appear to be universal across all proteins regardless of topology and size. Here, we systematically characterize the universal features of fast side chain motions in proteins by examining the conformational energy surfaces of individual residues obtained using enhanced sampling molecular dynamics simulation (618 free energy surfaces obtained from 0.94 s MD simulation). The side chain conformational free energy surfaces obtained using the adaptive biasing force (ABF) method for a set of eight proteins with different molecular weights and secondary structures are used to determine the methyl axial NMR order parameters (O axis 2), populationsmore » of side chain rotamer states (ρ), conformational entropies (S conf), probability fluxes, and activation energies for side chain inter-rotameric transitions. The free energy barriers separating side chain rotamer states range from 0.3 to 12 kcal/mol in all proteins and follow a trimodal distribution with an intense peak at ~5 kcal/mol and two shoulders at ~3 and ~7.5 kcal/mol, indicating that some barriers are more favored than others by proteins to maintain a balance between their conformational stability and flexibility. The origin and the influences of the trimodal barrier distribution on the distribution of O axis 2 and the side chain conformational entropy are discussed. A hierarchical grading of rotamer states based on the conformational free energy barriers, entropy, and probability flux reveals three distinct classes of side chains in proteins. A unique nonlinear correlation is established between O axis 2 and the side chain rotamer populations (ρ). In conclusion, the apparent universality in O axis 2 versus correlation, trimodal barrier distribution, and distinct characteristics of three classes of side chains observed among all proteins indicates a hidden regularity (or commonality) in the dynamical heterogeneity of fast side chain motions in proteins.« less

Recovery and fine structure variability of RGII sub-domains in wine (Vitis vinifera Merlot)

PubMed Central

Buffetto, F.; Ropartz, D.; Zhang, X. J.; Gilbert, H. J.; Guillon, F.; Ralet, M.-C.

2014-01-01

Background and Aims Rhamnogalacturonan II (RGII) is a structurally complex pectic sub-domain composed of more than 12 different sugars and 20 different linkages distributed in five side chains along a homogalacturonan backbone. Although RGII has long been described as highly conserved over plant evolution, recent studies have revealed variations in the structure of the polysaccharide. This study examines the fine structure variability of RGII in wine, focusing on the side chains A and B obtained after sequential mild acid hydrolysis. Specifically, this study aims to differentiate intrinsic structural variations in these RGII side chains from structural variations due to acid hydrolysis. Methods RGII from wine (Vitis vinifera Merlot) was sequentially hydrolysed with trifluoroacetic acid (TFA) and the hydrolysis products were separated by anion-exchange chromatography (AEC). AEC fractions or total hydrolysates were analysed by MALDI-TOF mass spectrometry. Key Results The optimal conditions to recover non-degraded side chain B, side chain A and RGII backbone were 0·1 m TFA at 40 °C for 16 h, 0·48 m TFA at 40 °C for 16 h (or 0·1 m TFA at 60 °C for 8 h) and 0·1 m TFA at 60 °C for 16 h, respectively. Side chain B was particularly prone to acid degradation. Side chain A and the RGII GalA backbone were partly degraded by 0·1 m TFA at 80 °C for 1–4 h. AEC allowed separation of side chain B, methyl-esterified side chain A and non-methyl-esterified side chain A. The structure of side chain A and the GalA backbone were highly variable. Conclusions Several modifications to the RGII structure of wine were identified. The observed dearabinosylation and deacetylation were primarily the consequence of acidic treatment, while variation in methyl-esterification, methyl-ether linkages and oxidation reflect natural diversity. The physiological significance of this variability, however, remains to be determined. PMID:24908680

Extraction, Scrub, and Strip Test Results for the Salt Waste Processing Facility Caustic Side Solvent Extraction Solvent Sample

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters, T. B.

An Extraction, Scrub, and Strip (ESS) test was performed on a sample of Salt Waste Processing Facility (SWPF) Caustic-Side Solvent Extraction (CSSX) solvent and salt simulant to determine cesium distribution ratios (D( Cs)), and cesium concentration in the strip effluent (SE) and decontaminated salt solution (DSS) streams; this data will be used by Parsons to help determine if the solvent is qualified for use at the SWPF. The ESS test showed acceptable performance of the solvent for extraction, scrub, and strip operations. The extraction D( Cs) measured 12.5, exceeding the required value of 8. This value is consistent with resultsmore » from previous ESS tests using similar solvent formulations. Similarly, scrub and strip cesium distribution ratios fell within acceptable ranges. This revision was created to correct an error. The previous revision used an incorrect set of temperature correction coefficients which resulted in slight deviations from the correct D( Cs) results.« less

Assessing the influence of side-chain and main-chain aromatic benzyltrimethyl ammonium on anion exchange membranes.

PubMed

Li, Xiuhua; Nie, Guanghui; Tao, Jinxiong; Wu, Wenjun; Wang, Liuchan; Liao, Shijun

2014-05-28

3,3'-Di(4″-methyl-phenyl)-4,4'-difluorodiphenyl sulfone (DMPDFPS), a new monomer with two pendent benzyl groups, was easily prepared by Suzuki coupling reaction in high yield. A series of side-chain type ionomers (PAES-Qs) containing pendant side-chain benzyltrimethylammonium groups, which linked to the backbone by alkaline resisting conjugated C-C bonds, were synthesized via polycondensation, bromination, followed by quaternization and alkalization. To assess the influence of side-chain and main-chain aromatic benzyltrimethylammonium on anion exchange membranes (AEMs), the main-chain type ionomers (MPAES-Qs) with the same backbone were synthesized following the similar procedure. GPC and (1)H NMR results indicate that the bromination shows no reaction selectivity of polymer configurations and ionizations of the side-chain type polymers display higher conversions than that of the main-chain type ones do. These two kinds of AEMs were evaluated in terms of ion exchange capacity (IEC), water uptake, swelling ratio, λ, volumetric ion exchange capacity (IECVwet), hydroxide conductivity, mechanical and thermal properties, and chemical stability, respectively. The side-chain type structure endows AEMs with lower water uptake, swelling ratio and λ, higher IECVwet, much higher hydroxide conductivity, more robust dimensional stability, mechanical and thermal properties, and higher stability in hot alkaline solution. The side-chain type cationic groups containing molecular configurations have the distinction of being practical AEMs and membrane electrode assemblies of AEMFCs.

Translocation of a Polymer Chain across a Nanopore: A Brownian Dynamics Simulation Study

NASA Technical Reports Server (NTRS)

Tian, Pu; Smith, Grant D.

2003-01-01

We carried out Brownian dynamics simulation studies of the translocation of single polymer chains across a nanosized pore under the driving of an applied field (chemical potential gradient). The translocation process can be either dominated by the entropic barrier resulted from restricted motion of flexible polymer chains or by applied forces (or chemical gradient across the wall), we focused on the latter case in our studies. Calculation of radius of gyrations at the two opposite sides of the wall shows that the polymer chains are not in equilibrium during the translocation process. Despite this fact, our results show that the one-dimensional diffusion and the nucleation model provide an excellent description of the dependence of average translocation time on the chemical potential gradients, the polymer chain length and the solvent viscosity. In good agreement with experimental results and theoretical predictions, the translocation time distribution of our simple model shows strong non-Gaussian characteristics. It is observed that even for this simple tubelike pore geometry, more than one peak of translocation time distribution can be generated for proper pore diameter and applied field strengths. Both repulsive Weeks-Chandler-Anderson and attractive Lennard-Jones polymer-nanopore interaction were studied, attraction facilitates the translocation process by shortening the total translocation time and dramatically improve the capturing of polymer chain. The width of the translocation time distribution was found to decrease with increasing temperature, increasing field strength, and decreasing pore diameter.

L-cysteine-derived ambidextrous gelators of aromatic solvents and ethanol/water mixtures.

PubMed

Pal, Amrita; Dey, Joykrishna

2013-02-19

A series of L-cysteine-derived double hydrocarbon chain amphiphilic gelators L-(3-alkyl-carbamoylsulfanyl)-2-(3-alkylurido)propionic acid with different hydrocarbon chain lengths (C6-C16) was designed and synthesized. These gelators efficiently gelate only aromatic solvents. The gelation ability increased with the increase of chain length up to C14, but then it dropped with further increase of chain length. The C12 and C14 derivatives also gelled ethanol/water mixtures. The gels were characterized by a number of methods, including FT-IR, NMR, and XRD spectroscopy, electron microscopy, and rheology. The amphiphiles were observed to form either flat lamellar or ribbonlike aggregates in aromatic solvents as well as in ethanol/water mixtures. The gelation in all the solvents employed was observed to be thermoreversible. The gel-to-sol transition temperature as well as mechanical strength of the organogels were observed to increase with the hydrocarbon chain length. Both types of gels of C8-C16 amphiphiles have gel-to-sol transition temperatures above the physiological temperature (310 K). FT-IR and variable temperature (1)H NMR measurements suggested that van der Waals interactions have major contribution in the gelation process. The gel-to-sol transition temperature and mechanical strength of the organogels in ethanol/water mixtures was observed to be higher than those of benzene organogel.

Coulomb repulsion in short polypeptides.

PubMed

Norouzy, Amir; Assaf, Khaleel I; Zhang, Shuai; Jacob, Maik H; Nau, Werner M

2015-01-08

Coulomb repulsion between like-charged side chains is presently viewed as a major force that impacts the biological activity of intrinsically disordered polypeptides (IDPs) by determining their spatial dimensions. We investigated short synthetic models of IDPs, purely composed of ionizable amino acid residues and therefore expected to display an extreme structural and dynamic response to pH variation. Two synergistic, custom-made, time-resolved fluorescence methods were applied in tandem to study the structure and dynamics of the acidic and basic hexapeptides Asp6, Glu6, Arg6, Lys6, and His6 between pH 1 and 12. (i) End-to-end distances were obtained from the short-distance Förster resonance energy transfer (sdFRET) from N-terminal 5-fluoro-l-tryptophan (FTrp) to C-terminal Dbo. (ii) End-to-end collision rates were obtained for the same peptides from the collision-induced fluorescence quenching (CIFQ) of Dbo by FTrp. Unexpectedly, the very high increase of charge density at elevated pH had no dynamical or conformational consequence in the anionic chains, neither in the absence nor in the presence of salt, in conflict with the common view and in partial conflict with accompanying molecular dynamics simulations. In contrast, the cationic peptides responded to ionization but with surprising patterns that mirrored the rich individual characteristics of each side chain type. The contrasting results had to be interpreted, by considering salt screening experiments, N-terminal acetylation, and simulations, in terms of an interplay of local dielectric constant and peptide-length dependent side chain charge-charge repulsion, side chain functional group solvation, N-terminal and side chain charge-charge repulsion, and side chain-side chain as well as side chain-backbone interactions. The common picture that emerged is that Coulomb repulsion between water-solvated side chains is efficiently quenched in short peptides as long as side chains are not in direct contact with each other or the main chain.

Simulation of macromolecule self-assembly in solution: A multiscale approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lavino, Alessio D., E-mail: alessiodomenico.lavino@studenti.polito.it; Barresi, Antonello A., E-mail: antonello.barresi@polito.it; Marchisio, Daniele L., E-mail: daniele.marchisio@polito.it

2015-12-17

One of the most common processes to produce polymer nanoparticles is to induce self-assembly by using the solvent-displacement method, in which the polymer is dissolved in a “good” solvent and the solution is then mixed with an “anti-solvent”. The polymer ability to self-assemble in solution is therefore determined by its structural and transport properties in solutions of the pure solvents and at the intermediate compositions. In this work, we focus on poly-ε-caprolactone (PCL) which is a biocompatible polymer that finds widespread application in the pharmaceutical and biomedical fields, performing simulation at three different scales using three different computational tools: fullmore » atomistic molecular dynamics (MD), population balance modeling (PBM) and computational fluid dynamics (CFD). Simulations consider PCL chains of different molecular weight in solution of pure acetone (good solvent), of pure water (anti-solvent) and their mixtures, and mixing at different rates and initial concentrations in a confined impinging jets mixer (CIJM). Our MD simulations reveal that the nano-structuring of one of the solvents in the mixture leads to an unexpected identical polymer structure irrespectively of the concentration of the two solvents. In particular, although in pure solvents the behavior of the polymer is, as expected, very different, at intermediate compositions, the PCL chain shows properties very similar to those found in pure acetone as a result of the clustering of the acetone molecules in the vicinity of the polymer chain. We derive an analytical expression to predict the polymer structural properties in solution at different solvent compositions and use it to formulate an aggregation kernel to describe the self-assembly in the CIJM via PBM and CFD. Simulations are eventually validated against experiments.« less

Diketopyrrolopyrrole-based Conjugated Polymers Bearing Branched Oligo(Ethylene Glycol) Side Chains for Photovoltaic Devices.

PubMed

Chen, Xingxing; Zhang, Zijian; Ding, Zicheng; Liu, Jun; Wang, Lixiang

2016-08-22

Conjugated polymers are essential for solution-processable organic opto-electronic devices. In contrast to the great efforts on developing new conjugated polymer backbones, research on developing side chains is rare. Herein, we report branched oligo(ethylene glycol) (OEG) as side chains of conjugated polymers. Compared with typical alkyl side chains, branched OEG side chains endowed the resulting conjugated polymers with a smaller π-π stacking distance, higher hole mobility, smaller optical band gap, higher dielectric constant, and larger surface energy. Moreover, the conjugated polymers with branched OEG side chains exhibited outstanding photovoltaic performance in polymer solar cells. A power conversion efficiency of 5.37 % with near-infrared photoresponse was demonstrated and the device performance could be insensitive to the active layer thickness. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tuning the thermal conductivity of solar cell polymers through side chain engineering.

PubMed

Guo, Zhi; Lee, Doyun; Liu, Yi; Sun, Fangyuan; Sliwinski, Anna; Gao, Haifeng; Burns, Peter C; Huang, Libai; Luo, Tengfei

2014-05-07

Thermal transport is critical to the performance and reliability of polymer-based energy devices, ranging from solar cells to thermoelectrics. This work shows that the thermal conductivity of a low band gap conjugated polymer, poly(4,8-bis-alkyloxybenzo[1,2-b:4,5-b']dithiophene-2,6-diyl-alt-(alkylthieno[3,4-b]thiophene-2-carboxylate)-2,6-diyl) (PBDTTT), for photovoltaic applications can be actively tuned through side chain engineering. Compared to the original polymer modified with short branched side chains, the engineered polymer using all linear and long side chains shows a 160% increase in thermal conductivity. The thermal conductivity of the polymer exhibits a good correlation with the side chain lengths as well as the crystallinity of the polymer characterized using small-angle X-ray scattering (SAXS) experiments. Molecular dynamics simulations and atomic force microscopy are used to further probe the molecular level local order of different polymers. It is found that the linear side chain modified polymer can facilitate the formation of more ordered structures, as compared to the branched side chain modified ones. The effective medium theory modelling also reveals that the long linear side chain enables a larger heat carrier propagation length and the crystalline phase in the bulk polymer increases the overall thermal conductivity. It is concluded that both the length of the side chains and the induced polymer crystallization are important for thermal transport. These results offer important guidance for actively tuning the thermal conductivity of conjugated polymers through molecular level design.

Biodegradable polyester films from renewable aleuritic acid: surface modifications induced by melt-polycondensation in air

NASA Astrophysics Data System (ADS)

Jesús Benítez, José; Alejandro Heredia-Guerrero, José; Inmaculada de Vargas-Parody, María; Cruz-Carrillo, Miguel Antonio; Morales-Flórez, Victor; de la Rosa-Fox, Nicolás; Heredia, Antonio

2016-05-01

Good water barrier properties and biocompatibility of long-chain biopolyesters like cutin and suberin have inspired the design of synthetic mimetic materials. Most of these biopolymers are made from esterified mid-chain functionalized ω-long chain hydroxyacids. Aleuritic (9,10,16-trihydroxypalmitic) acid is such a polyhydroxylated fatty acid and is also the major constituent of natural lac resin, a relatively abundant and renewable resource. Insoluble and thermostable films have been prepared from aleuritic acid by melt-condensation polymerization in air without catalysts, an easy and attractive procedure for large scale production. Intended to be used as a protective coating, the barrier's performance is expected to be conditioned by physical and chemical modifications induced by oxygen on the air-exposed side. Hence, the chemical composition, texture, mechanical behavior, hydrophobicity, chemical resistance and biodegradation of the film surface have been studied by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), atomic force microscopy (AFM), nanoindentation and water contact angle (WCA). It has been demonstrated that the occurrence of side oxidation reactions conditions the surface physical and chemical properties of these polyhydroxyester films. Additionally, the addition of palmitic acid to reduce the presence of hydrophilic free hydroxyl groups was found to have a strong influence on these parameters.

Folding and Function of a T4 Lysozyme Containing 10 Consecutive Alanines Illustrate the Redundancy of Information in an Amino Acid Sequence

NASA Astrophysics Data System (ADS)

Heinz, Dirk W.; Baase, Walt A.; Matthews, Brian W.

1992-05-01

Single and multiple Xaa -> Ala substitutions were constructed in the α-helix comprising residues 39-50 in bacteriophage T4 lysozyme. The variant with alanines at 10 consecutive positions (A40-49) folds normally and has activity essentially the same as wild type, although it is less stable. The crystal structure of this polyalanine mutant displays no significant change in the main-chain atoms of the helix when compared with the wild-type structure. The individual substitutions of the solvent-exposed residues Asn-40, Ser-44, and Glu-45 with alanine tend to increase the thermostability of the protein, whereas replacements of the buried or partially buried residues Lys-43 and Leu-46 are destabilizing. The melting temperature of the lysozyme in which Lys-43 and Leu-46 are retained and positions 40, 44, 45, 47, and 48 are substituted with alanine (i.e., A40-42/44-45/47-49) is increased by 3.1^circC relative to wild type at pH 3.0, but reduced by 1.6^circC at pH 6.7. In the case of the charged amino acids Glu-45 and Lys-48, the changes in melting temperature indicate that the putative salt bridge between these two residues contributes essentially nothing to the stability of the protein. The results clearly demonstrate that there is considerable redundancy in the sequence information in the polypeptide chain; not every amino acid is essential for folding. Also, further evidence is provided that the replacement of fully solvent-exposed residues within α-helices with alanines may be a general way to increase protein stability. The general approach may permit a simplification of the protein folding problem by retaining only amino acids proven to be essential for folding and replacing the remainder with alanine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tachi, N.; Shimotori, S.; Naruse, N.

Synthetic adhesives are widely used in various industries as well as at home. Adhesives usually contain several organic solvents which easily vaporize. Exposure can cause aplastic anemia and polyneuropathy in adults. Chronic glue sniffing results in aplastic anemia, polyneuropathy, and muscular atrophy. Inhalation of the solvent contained in adhesives, such as n-hexane, toluene, xylene, and benzene by pregnant animals can decrease the number of live fetuses and retard fetal growth. In humans, the risk of spontaneous abortion is increased in workers exposed to organic solvents. However, information is still limited about the effects of exposure to organic solvents vaporized frommore » adhesives on fetuses. In the present study, female mice were exposed throughout pregnancy to organic solvents vaporized from an adhesive to clarify the effects of the inhalation on progeny. 19 refs., 1 fig., 4 tabs.« less

``Effect of Polyalkylthiophene Microstructure on Physical and Optoelectronic Properties''

NASA Astrophysics Data System (ADS)

Minkler, Michael J., Jr.; Beckingham, Bryan S.

Conjugated polymers have been of widespread interest as flexible semiconductors for organic electronic devices such as solar cells, field effect transistor,s and light-emitting diodes. Of particular interest have been alkyl-substituted polythiophenes due to their well-controlled synthesis, favorable optoelectronic properties, and solubility in organic solvents. Importantly, relatively small changes to the chemical microstructure in poly(3-alkylthiophenes) (P3ATs) can have a significant effect on the resulting physical and optoelectronic properties. For instance, the addition of aliphatic side chains onto unsubstituted polythiophene provides solubility but also greatly decreases conductivity in comparison to unsubstituted polythiophene (PT). In this work, we use Grignard metathesis polymerization to synthesize poly(3-hexylthiophene) (P3HT), PT, and statistical copolymers (P[3HT-co-T]) over a range of compositions. We examine the physical properties (melting temperature, crystallinity, etc) by differential scanning calorimetry and wide angle X-ray scattering, optoelectronic properties by UV/Vis spectroscopy, and solubility in organic solvents of these copolymers in order to gain insights into the interplay of microstructure and properties in this class of materials.

A practical method for measuring the ion exchange capacity decrease of hydroxide exchange membranes during intrinsic degradation

NASA Astrophysics Data System (ADS)

Kreuer, Klaus-Dieter; Jannasch, Patric

2018-01-01

In this work we present a practical thermogravimetric method for quantifying the IEC (ion exchange capacity) decrease of hydroxide exchange membranes (HEMs) during intrinsic degradation mainly occurring through nucleophilic attack of the anion exchanging group by hydroxide ions. The method involves measuring weight changes under controlled temperature and relative humidity. These conditions are close to these in a fuel cell, i.e. the measured degradation rate includes all effects originating from the polymeric structure, the consumption of hydroxide ions and the release of water. In particular, this approach involves no added solvents or base, thereby avoiding inaccuracies that may arise in other methods due to the presence of solvents (other than water) or co-ions (such as Na+ or K+). We demonstrate the method by characterizing the decomposition of membranes consisting of poly(2,6-dimethyl-1,4-phenylene oxide) functionalized with trimethyl-pentyl-ammonium side chains. The decomposition rate is found to depend on temperature, relative humidity RH (controlling the hydration number λ) and the total water content (controlled by the actual IEC and RH).

Exploring ways to control the properties of polymer thin films

NASA Astrophysics Data System (ADS)

Clough, Andrew R.

Understanding the causes of deviations from bulk-like properties observed in polymer thin films is of interest both from a fundamental standpoint and in order to tailor the properties of polymer thin films used by industry as coatings and in the production of microelectronic devices. As thicknesses are decreased below 100 nm, interfacial effects start to become important. In addition, a confinement effect occurs when the film thickness becomes comparable to the unperturbed size of the polymer chain. In this thesis, we modify polymer films in a controllable way in order to study how some of these properties may be related and potentially adjusted. One of these properties is the glass transition temperature, which is seen to vary with the film thickness for films thinner than 100 nm. While there appears to be a consensus that the variation is attributable to the interactions the polymer has with the film interfaces, important questions concerning how the observed changes may affect the onset of large scale, liquid-like motions in the films have been seldom investigated. We modify the substrate interface with grafted polymer chains, which is known to instill interfacial slippage, to investigate the relation, if any, between the glass transition temperature and large scale chain motions in the films. As another part of the effort to find ways to control the properties of polymer films, we study the effect of swelling films with solvents of different qualities. Studies have shown that modifying the solvent quality used when preparing films by spin-coating, in which solvent from a polymer solution is rapidly removed to form thin uniform films, can affect some properties by modifying the degree of inter-chain entanglement in the film. As it is often difficult to spin-coat films when the solvent is poor, we investigate whether solvent swelling can also be used to modify this entanglement. We find that solvent swelling is able to modify the degree of entanglement in the films. Most importantly, swelling with a poor solvent allows us to reduce the degree of inter-chain entanglement, bringing the film further from equilibrium.

Amyloid-like self-assembly of peptide sequences from the adenovirus fiber shaft: insights from molecular dynamics simulations.

PubMed

Tamamis, Phanourios; Kasotakis, Emmanouil; Mitraki, Anna; Archontis, Georgios

2009-11-26

The self-assembly of peptides and proteins into nanostructures is related to the fundamental problems of protein folding and misfolding and has potential applications in medicine, materials science and nanotechnology. Natural peptides, corresponding to sequence repeats from self-assembling proteins, may constitute elementary building blocks of such nanostructures. In this work, we study by implicit-solvent replica-exchange simulations the self-assembly of two amyloidogenic sequences derived from the naturally occurring fiber shaft of the adenovirus, the octapeptide NSGAITIG (asparagine-serine-glycine-alanine-isoleucine-threonine-isoleucine-glycine) and its hexapeptide counterpart, GAITIG. In accordance with their amyloidogenic capacity, both peptides form readily intermolecular beta-sheets, stabilized by extensive main- and side-chain contacts involving the C-terminal moieties (segments 3-8 and 2-6, respectively). The structural and energetic properties of these sheets are analyzed extensively. The N-terminal residues Asn1 and Ser2 of the octapeptide remain disordered in the sheets, suggesting that these residues are exposed at the exterior of the fibrils and accessible. On the basis of insight provided by the simulations, cysteine residues were recently substituted at positions 1 and 2 of NSGAITIG; the newly designed peptides maintain their amyloidogenic properties and can bind to silver, gold and platinum nanoparticles [Kasotakis et al. Biopolymers 2009, 92, 164-172]. Computational investigation can identify suitable positions for rational modification of peptide building blocks, aiming at the fabrication of novel biomaterials.

Raman signature of the non-hydrogen-bonded tryptophan side chain in proteins: experimental and ab initio spectra of 3-methylindole in the gas phase

NASA Astrophysics Data System (ADS)

Combs, Amanda; McCann, Kathleen; Autrey, Daniel; Laane, Jaan; Overman, Stacy A.; Thomas, George J.

2005-02-01

3-Methylindole (3MI), which serves as a structural model for the tryptophan side chain in proteins, has been investigated using vapor phase Raman spectroscopy. The vapor phase spectrum of 3MI identifies the Raman signature of the indolyl moiety free of intermolecular interaction and extends previously reported solution Raman studies of 3MI and related tryptophan derivatives. The Raman spectrum of 3MI vapor is also complemented here with newly obtained vapor phase infrared data and ab initio calculations to refine and extend previous vibrational assignments. The present results provide an improved basis for assessing the dependence of the indolyl Raman signature on the local environment of the tryptophan side chain of proteins. The principal conclusions of this work are the following. (i) The vapor phase 3MI molecule exhibits Raman bands at 3506, 1585, 1409, 1349/1341 (Fermi doublet) and 881 cm-1, which differ greatly from their counterparts in the Raman spectrum of 3MI liquid and thus serve as spectral markers of the indolyl ring environment. (ii) The Fermi doublet relative intensity ratio (I1/I2, where I1 and I2 are, respectively, the Raman intensities of the higher and lower wavenumber components of the doublet) is highly sensitive to the state of 3MI condensation, consistent with the previously reported sensitivity of I1/I2 to solvent polarity. The maximum value of the intensity ratio (I1/I2=3.0) is observed for 3MI vapor, while the minimum value (I1/I2=0.43) is observed for 3MI in CHCl3 solution. Implications of the present results for Raman analysis of hydrogen bonding states, hydrophilic interactions and hydrophobic interactions of tryptophan residues in proteins are considered.

Polder maps: Improving OMIT maps by excluding bulk solvent

DOE PAGES

Liebschner, Dorothee; Afonine, Pavel V.; Moriarty, Nigel W.; ...

2017-02-01

The crystallographic maps that are routinely used during the structure-solution workflow are almost always model-biased because model information is used for their calculation. As these maps are also used to validate the atomic models that result from model building and refinement, this constitutes an immediate problem: anything added to the model will manifest itself in the map and thus hinder the validation. OMIT maps are a common tool to verify the presence of atoms in the model. The simplest way to compute an OMIT map is to exclude the atoms in question from the structure, update the corresponding structure factorsmore » and compute a residual map. It is then expected that if these atoms are present in the crystal structure, the electron density for the omitted atoms will be seen as positive features in this map. This, however, is complicated by the flat bulk-solvent model which is almost universally used in modern crystallographic refinement programs. This model postulates constant electron density at any voxel of the unit-cell volume that is not occupied by the atomic model. Consequently, if the density arising from the omitted atoms is weak then the bulk-solvent model may obscure it further. A possible solution to this problem is to prevent bulk solvent from entering the selected OMIT regions, which may improve the interpretative power of residual maps. This approach is called a polder (OMIT) map. Polder OMIT maps can be particularly useful for displaying weak densities of ligands, solvent molecules, side chains, alternative conformations and residues both in terminal regions and in loops. As a result, the tools described in this manuscript have been implemented and are available in PHENIX.« less

Synthesis of Sulfotyrosine-Containing Peptides by Incorporating Fluorosulfated Tyrosine Using an Fmoc-Based Solid-Phase Strategy.

PubMed

Chen, Wentao; Dong, Jiajia; Li, Suhua; Liu, Yu; Wang, Yujia; Yoon, Leonard; Wu, Peng; Sharpless, K Barry; Kelly, Jeffery W

2016-01-26

Tyrosine O-sulfation is a common protein post-translational modification that regulates many biological processes, including leukocyte adhesion and chemotaxis. Many peptides with therapeutic potential contain one or more sulfotyrosine residues. We report a one-step synthesis for Fmoc-fluorosulfated tyrosine. An efficient Fmoc-based solid-phase peptide synthetic strategy is then introduced for incorporating the fluorosulfated tyrosine residue into peptides of interest. Standard simultaneous peptide-resin cleavage and removal of the acid-labile side-chain protecting groups affords the crude peptides containing fluorosulfated tyrosine. Basic ethylene glycol, serving both as solvent and reactant, transforms the fluorosulfated tyrosine peptides into sulfotyrosine peptides in high yield. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Application of Ligand-Mapping Molecular Dynamics Simulations to the Rational Design of Peptidic Modulators of Protein-Protein Interactions.

PubMed

Tan, Yaw Sing; Spring, David R; Abell, Chris; Verma, Chandra S

2015-07-14

A computational ligand-mapping approach to detect protein surface pockets that interact with hydrophobic moieties is presented. In this method, we incorporated benzene molecules into explicit solvent molecular dynamics simulations of various protein targets. The benzene molecules successfully identified the binding locations of hydrophobic hot-spot residues and all-hydrocarbon cross-links from known peptidic ligands. They also unveiled cryptic binding sites that are occluded by side chains and the protein backbone. Our results demonstrate that ligand-mapping molecular dynamics simulations hold immense promise to guide the rational design of peptidic modulators of protein-protein interactions, including that of stapled peptides, which show promise as an exciting new class of cell-penetrating therapeutic molecules.

End-anchored polymers in good solvents from the single chain limit to high anchoring densities.

PubMed

Whitmore, Mark D; Grest, Gary S; Douglas, Jack F; Kent, Michael S; Suo, Tongchuan

2016-11-07

An increasing number of applications utilize grafted polymer layers to alter the interfacial properties of solid substrates, motivating refinement in our theoretical understanding of such layers. To assess existing theoretical models of them, we have investigated end-anchored polymer layers over a wide range of grafting densities, σ, ranging from a single chain to high anchoring density limits, chain lengths ranging over two orders of magnitude, for very good and marginally good solvent conditions. We compare Monte Carlo and molecular dynamics simulations, numerical self-consistent field calculations, and experimental measurements of the average layer thickness, h, with renormalization group theory, the Alexander-de Gennes mushroom theory, and the classical brush theory. Our simulations clearly indicate that appreciable inter-chain interactions exist at all simulated areal anchoring densities so that there is no mushroom regime in which the layer thickness is independent of σ. Moreover, we find that there is no high coverage regime in which h follows the predicted scaling, h ∼ Nσ 1/3 , for classical polymer brushes either. Given that no completely adequate analytic theory seems to exist that spans wide ranges of N and σ, we applied scaling arguments for h as a function of a suitably defined reduced anchoring density, defined in terms of the solution radius of gyration of the polymer chains and N. We find that such a scaling approach enables a smooth, unified description of h in very good solvents over the full range of anchoring density and chain lengths, although this type of data reduction does not apply to marginal solvent quality conditions.

Inhalation developmental toxicology studies: Teratology study of n-hexane in rats: Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mast, T.J.

The straight chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent used in industrial, academic, and smaller commercial environments. The significant opportunity for women of child-bearing age to be exposed to this chemical prompted the undertaking of a study to assess the developmental toxicity of n-hexane in an animal model. Timed-pregnant (30 animals per group) and virgin (10 animals per group) Sprague-Dawley rats were exposed to 0 (filtered air), 200, 1000, and 5000 ppM n-hexane (99.9% purity) vapor in inhalation chambers for 20 h/day for a period of 14 consecutive days. Sperm-positive females were exposed for 6 to 19 days ofmore » gestation (dg) and virgins were exposed concurrently for 14 consecutive days. The day of sperm detection was designated as 0 dg for mated females. Adult female body weights were monitored prior to, throughout the exposure period, and at sacrifice. Uterine, placental, and fetal body weights were obtained for gravid females at sacrifice. Implants were enumerated and their status recorded as live fetus, early or late resorption, or dead. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 16 refs., 3 figs., 7 tabs.« less

Mitigation of reversible self-association and viscosity in a human IgG1 monoclonal antibody by rational, structure-guided Fv engineering

PubMed Central

Geoghegan, James C.; Fleming, Ryan; Damschroder, Melissa; Bishop, Steven M.; Sathish, Hasige A.; Esfandiary, Reza

2016-01-01

ABSTRACT Undesired solution behaviors such as reversible self-association (RSA), high viscosity, and liquid-liquid phase separation can introduce substantial challenges during development of monoclonal antibody formulations. Although a global mechanistic understanding of RSA (i.e., native and reversible protein-protein interactions) is sufficient to develop robust formulation controls, its mitigation via protein engineering requires knowledge of the sites of protein-protein interactions. In the study reported here, we coupled our previous hydrogen-deuterium exchange mass spectrometry findings with structural modeling and in vitro screening to identify the residues responsible for RSA of a model IgG1 monoclonal antibody (mAb-C), and rationally engineered variants with improved solution properties (i.e., reduced RSA and viscosity). Our data show that mutation of either solvent-exposed aromatic residues within the heavy and light chain variable regions or buried residues within the heavy chain/light chain interface can significantly mitigate RSA and viscosity by reducing the IgG's surface hydrophobicity. The engineering strategy described here highlights the utility of integrating complementary experimental and in silico methods to identify mutations that can improve developability, in particular, high concentration solution properties, of candidate therapeutic antibodies. PMID:27050875

Peptide chain dynamics in light and heavy water: zooming in on internal friction.

PubMed

Schulz, Julius C F; Schmidt, Lennart; Best, Robert B; Dzubiella, Joachim; Netz, Roland R

2012-04-11

Frictional effects due to the chain itself, rather than the solvent, may have a significant effect on protein dynamics. Experimentally, such "internal friction" has been investigated by studying folding or binding kinetics at varying solvent viscosity; however, the molecular origin of these effects is hard to pinpoint. We consider the kinetics of disordered glycine-serine and α-helix forming alanine peptides and a coarse-grained protein folding model in explicit-solvent molecular dynamics simulations. By varying the solvent mass over more than two orders of magnitude, we alter only the solvent viscosity and not the folding free energy. Folding dynamics at the near-vanishing solvent viscosities accessible by this approach suggests that solvent and internal friction effects are intrinsically entangled. This finding is rationalized by calculation of the polymer end-to-end distance dynamics from a Rouse model that includes internal friction. An analysis of the friction profile along different reaction coordinates, extracted from the simulation data, demonstrates that internal as well as solvent friction varies substantially along the folding pathways and furthermore suggests a connection between friction and the formation of hydrogen bonds upon folding. © 2012 American Chemical Society

Effects of a mutation on the folding mechanism of a beta-hairpin.

PubMed

Juraszek, Jarek; Bolhuis, Peter G

2009-12-17

The folding mechanism of a protein is determined by its primary sequence. Yet, how the mechanism is changed by a mutation is still poorly understood, even for basic secondary structures such as beta-hairpins. We perform an extensive simulation study of the effects of mutating the GB1 beta-hairpin into Trpzip4 (Y5W, F12W, V14W) on the folding mechanism. While Trpzip4 has a much more stable native state due to very strong hydrophobic interactions of the side chains, its folding rate does not differ significantly from the wild type beta-hairpin. We sample the free-energy landscapes of both hairpins with Replica Exchange Molecular Dynamics (REMD) and identify the four (meta)stable states (U, H, F, and N). Using Transition Path Sampling (TPS), we then harvest ensembles of unbiased pathways between the H and F states and between the F and N states to investigate the unbiased folding mechanisms. In both hairpins, the hydrophobic collapse (U-H) is followed by the middle hydrogen bond formation (H-F), and finally a closing of the strands in a zipper-like fashion (F-N). For the Trpzip4, the path ensembles indicate that the final F-N step is much more difficult than for GB1 and involves partial unfolding, rezipping of hydrogen bonds, and rearrangement of the Trp-14 side chain. For the rate-limiting (H-F) step, the path ensembles show that in GB1 desolvation and strand closure go hand in hand, while in Trpzip4 desolvation is decoupled from strand closure. Nevertheless, likelihood maximization shows that the reaction coordinate for both hairpins remains the interstrand distance. We conclude that the folding mechanism of both hairpins is a combination of hydrophobic collapse and zipping of hydrogen bonds but that the zipper mechanism is more visible in Trpzip4. A major difference between the two hairpins is that in the transition state of the rate-limiting step for Trpzip4 one tryptophan is exposed to the solvent due to steric hindrance, making the folding mechanism more complex and leading to an increased F-N barrier. Thus, our results show in atomistic detail how a mutation leads to a different folding mechanism and results in a more frustrated folding free-energy landscape.

Separating effective high density polyethylene segments from olefin block copolymers using high temperature liquid chromatography with a preloaded discrete adsorption promoting solvent barrier.

PubMed

Chatterjee, Tirtha; Rickard, Mark A; Pearce, Eric; Pangburn, Todd O; Li, Yongfu; Lyons, John W; Cong, Rongjuan; deGroot, A Willem; Meunier, David M

2016-09-23

Recent advances in catalyst technology have enabled the synthesis of olefin block copolymers (OBC). One type is a "hard-soft" OBC with a high density polyethylene (HDPE) block and a relatively low density polyethylene (VLDPE) block targeted as thermoplastic elastomers. Presently, one of the major challenges is to fractionate HDPE segments from the other components in an experimental OBC sample (block copolymers and VLDPE segments). Interactive high temperature liquid chromatography (HTLC) is ineffective for OBC separation as the HDPE segments and block copolymer chains experience nearly identical enthalpic interactions with the stationary phase and co-elute. In this work we have overcome this challenge by using liquid chromatography under the limiting conditions of desorption (LC LCD). A solvent plug (discrete barrier) is introduced in front of the sample which specifically promotes the adsorption of HDPE segments on the stationary phase (porous graphitic carbon). Under selected thermodynamic conditions, VLDPE segments and block copolymer chains crossed the barrier while HDPE segments followed the pore-included barrier solvent and thus enabled separation. The barrier solvent composition was optimized and the chemical composition of fractionated polymer chains was investigated as a function of barrier solvent strength using an online Fourier-transform infrared (FTIR) detector. Our study revealed that both the HDPE segments as well as asymmetric block copolymer chains (HDPE block length≫VLDPE block length) are retained in the separation and the barrier strength can be tailored to retain a particular composition. At the optimum barrier solvent composition, this method can be applied to separate effective HDPE segments from the other components, which has been demonstrated using an experimental OBC sample. Copyright © 2016 Elsevier B.V. All rights reserved.

Binding of cationic pentapeptides with modified side chain lengths to negatively charged lipid membranes: Complex interplay of electrostatic and hydrophobic interactions.

PubMed

Hoernke, Maria; Schwieger, Christian; Kerth, Andreas; Blume, Alfred

2012-07-01

Basic amino acids play a key role in the binding of membrane associated proteins to negatively charged membranes. However, side chains of basic amino acids like lysine do not only provide a positive charge, but also a flexible hydrocarbon spacer that enables hydrophobic interactions. We studied the influence of hydrophobic contributions to the binding by varying the side chain length of pentapeptides with ammonium groups starting with lysine to lysine analogs with shorter side chains, namely omithine (Orn), alpha, gamma-diaminobutyric acid (Dab) and alpha, beta-diaminopropionic acid (Dap). The binding to negatively charged phosphatidylglycerol (PG) membranes was investigated by calorimetry, FT-infrared spectroscopy (FT-IR) and monolayer techniques. The binding was influenced by counteracting and sometimes compensating contributions. The influence of the bound peptides on the lipid phase behavior depends on the length of the peptide side chains. Isothermal titration calorimetry (ITC) experiments showed exothermic and endothermic effects compensating to a different extent as a function of side chain length. The increase in lipid phase transition temperature was more significant for peptides with shorter side chains. FTIR-spectroscopy revealed changes in hydration of the lipid bilayer interface after peptide binding. Using monolayer techniques, the contributions of electrostatic and hydrophobic effects could clearly be observed. Peptides with short side chains induced a pronounced decrease in surface pressure of PG monolayers whereas peptides with additional hydrophobic interactions decreased the surface pressure much less or even lead to an increase, indicating insertion of the hydrophobic part of the side chain into the lipid monolayer.

Biodegradation of diesel fuel by a microbial consortium in the presence of 1-alkoxymethyl-2-methyl-5-hydroxypyridinium chloride homologues.

PubMed

Chrzanowski, Lukasz; Stasiewicz, Monika; Owsianiak, Mikołaj; Szulc, Alicja; Piotrowska-Cyplik, Agnieszka; Olejnik-Schmidt, Agnieszka K; Wyrwas, Bogdan

2009-09-01

Fast development of ionic liquids as gaining more and more attention valuable chemicals will undoubtedly lead to environmental pollution. New formulations and application of ionic liquids may result in contamination in the presence of hydrophobic compounds, such as petroleum mixtures. We hypothesize that in the presence of diesel fuel low-water-soluble ionic liquids may become more toxic to hydrocarbon-degrading microorganisms. In this study the influence of 1-alkoxymethyl-2-methyl-5-hydroxypyridinium chloride homologues (side-chain length from C(3) to C(18)) on biodegradation of diesel fuel by a bacterial consortium was investigated. Whereas test performed for the consortium cultivated on disodium succinate showed that toxicity of the investigated ionic liquids decreased with increase in side-chain length, only higher homologues (C(8)-C(18)) caused a decrease in diesel fuel biodegradation. As a result of exposure to toxic compounds also modification in cell surface hydrophobicity was observed (MATH). Disulphine blue active substances method was employed to determine partitioning index of ionic liquids between water and diesel fuel phase, which varied from 1.1 to 51% for C(3) and C(18) homologues, respectively. We conclude that in the presence of hydrocarbons acting as a solvent, the increased bioavailability of hydrophobic homologues is responsible for the decrease in biodegradation efficiency of diesel fuel.

High-Performance Visible-Blind UV Phototransistors Based on n-Type Naphthalene Diimide Nanomaterials.

PubMed

Song, Inho; Lee, Seung-Chul; Shang, Xiaobo; Ahn, Jaeyong; Jung, Hoon-Joo; Jeong, Chan-Uk; Kim, Sang-Wook; Yoon, Woojin; Yun, Hoseop; Kwon, O-Pil; Oh, Joon Hak

2018-04-11

This study investigates the performance of single-crystalline nanomaterials of wide-band gap naphthalene diimide (NDI) derivatives with methylene-bridged aromatic side chains. Such materials are found to be easily used as high-performance, visible-blind near-UV light detectors. NDI single-crystalline nanoribbons are assembled using a simple solution-based process (without solvent-inclusion problems), which is then applied to organic phototransistors (OPTs). Such OPTs exhibit excellent n-channel transistor characteristics, including an average electron mobility of 1.7 cm 2 V -1 s -1 , sensitive UV detection properties with a detection limit of ∼1 μW cm -2 , millisecond-level responses, and detectivity as high as 10 15 Jones, demonstrating the highly sensitive organic visible-blind UV detectors. The high performance of our OPTs originates from the large face-to-face π-π stacking area between the NDI semiconducting cores, which is facilitated by methylene-bridged aromatic side chains. Interestingly, NDI-based nanoribbon OPTs exhibit a distinct visible-blind near-UV detection with an identical detection limit, even under intense visible light illumination (for example, 10 4 times higher intensity than UV light intensity). Our findings demonstrate that wide-band gap NDI-based nanomaterials are highly promising for developing high-performance visible-blind UV photodetectors. Such photodetectors could potentially be used for various applications including environmental and health-monitoring systems.

The presence of functional groups key for biodegradation in ionic liquids: effect on gas solubility.

PubMed

Deng, Yun; Morrissey, Saibh; Gathergood, Nicholas; Delort, Anne-Marie; Husson, Pascale; Costa Gomes, Margarida F

2010-03-22

The effect of the incorporation of either ester or ester and ether functions into the side chain of an 1-alkyl-3-methylimidazolium cation on the physico-chemical properties of ionic liquids containing bis(trifluoromethylsulfonyl)imide or octylsulfate anions is studied. It is believed that the introduction of an ester function into the cation of the ionic liquids greatly increases their biodegradability. The density of three such ionic liquids is measured as a function of temperature, and the solubility of four gases-carbon dioxide, ethane, methane, and hydrogen-is determined between 303 K and 343 K and at pressures close to atmospheric level. Carbon dioxide is the most soluble gas, followed by ethane and methane; the mole fraction solubilities vary from 1.8 x 10(-3) to 3.7 x 10(-2). These solubilities are of the same order of magnitude as those determined for alkylimidazolium-based ionic liquids. The chemical modification of the alkyl side chain does not result in a significant change of the solvation properties of the ionic liquid. All of the solubilities decrease with increasing temperature, corresponding to an exothermal solvation process. From the variation of this property with temperature, the thermodynamic functions of solvation (Gibbs energy, enthalpy, and entropy) are calculated and provide information about the solute-solvent interactions and the molecular structure of the solutions.

Combination of Markov state models and kinetic networks for the analysis of molecular dynamics simulations of peptide folding.

PubMed

Radford, Isolde H; Fersht, Alan R; Settanni, Giovanni

2011-06-09

Atomistic molecular dynamics simulations of the TZ1 beta-hairpin peptide have been carried out using an implicit model for the solvent. The trajectories have been analyzed using a Markov state model defined on the projections along two significant observables and a kinetic network approach. The Markov state model allowed for an unbiased identification of the metastable states of the system, and provided the basis for commitment probability calculations performed on the kinetic network. The kinetic network analysis served to extract the main transition state for folding of the peptide and to validate the results from the Markov state analysis. The combination of the two techniques allowed for a consistent and concise characterization of the dynamics of the peptide. The slowest relaxation process identified is the exchange between variably folded and denatured species, and the second slowest process is the exchange between two different subsets of the denatured state which could not be otherwise identified by simple inspection of the projected trajectory. The third slowest process is the exchange between a fully native and a partially folded intermediate state characterized by a native turn with a proximal backbone H-bond, and frayed side-chain packing and termini. The transition state for the main folding reaction is similar to the intermediate state, although a more native like side-chain packing is observed.

Langmuir-Blodgett Films of Aromatic Schiff’s Bases Functionalized in the Side Chains of Polymethacrylate

DTIC Science & Technology

1991-05-03

Report No. 21 - Latigmuir-Blodgett Films of Aromatic Schiffs Bases , K Fuctionalized in the Side Chains of Polymethacrylate by T. Takahashi, P. Miller...aromatic Schiff’s bases functionalized in the side chains of Polymethacrylate T. Takahashi**, P. Miller*, Y. M. Chen*, L. Samuelson***, D. Galotti, B...has been investigated for polymers in which nonlinear optical (NLO) moieties are attachcd i, the side chain of polymethacrylate (PMA) backbone. Polymer

Effect of unsaturation on the absorption of ethane and ethylene in imidazolium-based ionic liquids.

PubMed

Moura, Leila; Mishra, Manas; Bernales, Varinia; Fuentealba, Patricio; Padua, Agilio A H; Santini, Catherine C; Costa Gomes, Margarida F

2013-06-20

The influence of the presence of imidazolium side chain unsaturation on the solubility of ethane and ethylene was studied in three ionic liquids: 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide-saturated alkyl side-chain in the cation; 1-methyl-3-(buten-3-yl)imidazolium bis(trifluorosulfonyl)imide-double bond in the side-chain of the cation; and 1-methyl-3-benzylimidazolium bis(trifluorosulfonyl)imide-benzyl group in the side-chain of the cation. The solubility of both gases decreases when the side-chain of the cations is functionalized with an unsaturated group. This can be explained by a less favorable enthalpy of solvation. The difference of solubility between ethane and ethylene can be explained from a balance of enthalpic and entropic factors: for the ionic liquid with the saturated alkyl side-chain and the benzyl-substituted side-chain, it is the favorable entropy of solvation that explains the larger ethylene solubility, whereas in the case of the saturated side-chain, it is the more favorable enthalpy of solvation. Molecular simulation allowed the identification of the mechanisms of solvation and the preferential solvation sites for each gas in the different ionic liquids. Simulations have shown that the entropy of solvation is more favorable when the presence of the gas weakens the cation-anion interactions or when the gas can be solvated near different sites of the ionic liquid.

Direct Determination of Site-Specific Noncovalent Interaction Strengths of Proteins from NMR-Derived Fast Side Chain Motional Parameters.

PubMed

Rajeshwar T, Rajitha; Krishnan, Marimuthu

2017-05-25

A novel approach to accurately determine residue-specific noncovalent interaction strengths (ξ) of proteins from NMR-measured fast side chain motional parameters (O axis 2 ) is presented. By probing the environmental sensitivity of side chain conformational energy surfaces of individual residues of a diverse set of proteins, the microscopic connections between ξ, O axis 2 , conformational entropy (S conf ), conformational barriers, and rotamer stabilities established here are found to be universal among proteins. The results reveal that side chain flexibility and conformational entropy of each residue decrease with increasing ξ and that for each residue type there exists a critical range of ξ, determined primarily by the mean side chain conformational barriers, within which flexibility of any residue can be reversibly tuned from highly flexible (with O axis 2 ∼ 0) to highly restricted (with O axis 2 ∼ 1) by increasing ξ by ∼3 kcal/mol. Beyond this critical range of ξ, both side chain flexibility and conformational entropy are insensitive to ξ. The interrelationships between conformational dynamics, conformational entropy, and noncovalent interactions of protein side chains established here open up new avenues to probe perturbation-induced (for example, ligand-binding, temperature, pressure) changes in fast side chain dynamics and thermodynamics of proteins by comparing their conformational energy surfaces in the native and perturbed states.

Formation of hydroxyl-functionalized stilbenoid molecular sieves at the liquid/solid interface on top of a 1-decanol monolayer.

PubMed

Bellec, Amandine; Arrigoni, Claire; Douillard, Ludovic; Fiorini-Debuisschert, Céline; Mathevet, Fabrice; Kreher, David; Attias, André-Jean; Charra, Fabrice

2014-10-31

Specific molecular tectons can be designed to form molecular sieves through self-assembly at the solid-liquid interface. After demonstrating a model tecton bearing apolar alkyl chains, we then focus on a modified structure involving asymmetric functionalization of some alkyl chains with polar hydroxyl groups in order to get chemical selectivity in the sieving. As the formation of supramolecular self-assembled networks strongly depends on molecule-molecule, molecule-substrate and molecule-solvent interactions, we compared the tectons' self-assembly on graphite for two types of solvent. We demonstrate the possibility to create hydroxylated stilbenoid molecular sieves by using 1-decanol as a solvent. Interestingly, with this solvent, the porous network is developed on top of a 1-decanol monolayer.

Personality and long term exposure to organic solvents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lindstroem, K.; Martelin, T.

1980-01-01

Personality, especially emotional reactions of two solvent exposed groups and a nonexposed reference group were described by means of 20 formal, content and check-list type of Rorschach variables. Another objective of the study was to explore the suitability and psychological meaning of other types of Rorschach variables than those applied earlier in the field of behavioral toxicology. The factor analyses grouped the applied variables into factors of Productivity, Ego Strength, Control of Emotionality, Defensive Introversion and Aggressiveness. One solvent group, a patient groups (N.53), was characterized by a high number of Organic signs and a low Genetic Level, indicating possiblemore » psychoorganic deterioration. The other solvent group, styrene exposed but subjectively healthy (N.98), was characterized by few emotional reactions, low Anxiety and a low number of Neurotic Signs. the long duration of exposure of the solvent patient group (mean 10.2 +/- 8.7 years) was related to variables of the Productivity factor, a finding that indicates a possible better adjustment of those exposed for a longer time. The duration of exposure of the styrene exposed group (mean 4.9 +/- 3.2 years) revealed a very slight relation to personality variables, but the mean urinary mandelic acid concentration, indicating the level of styrene exposure, correlated with increased emotional reactions. For the most part definite causal conclusions could not be drawn because of the cross-sectional design of the study.« less

Solvent inhalation (toluene and n-hexane) during the brain growth spurt impairs the maturation of frontal, parietal and occipital cerebrocortical neurons in rats.

PubMed

Pascual, Rodrigo; Aedo, Luz; Meneses, Juan Carlos; Vergara, Daniela; Reyes, Alvaro; Bustamante, Carlos

2010-10-01

Solvent abuse during pregnancy may cause "fetal solvent syndrome", which is characterized by mild brain atrophy and associated with behavioral, cognitive, and emotional abnormalities. The present study investigated whether solvent inhalation during the preweaning period (P2-P21) alters the morphological maturation of frontal, parietal, and occipital cortical neurons. Twelve hours after delivery (postnatal day 0, P0), litters were cross-fostered, culled to 8 pups/dam and housed together with a dam in standard laboratory cages. Litters were randomly assigned to the "air-only" group (n=64, 8 litters) and to the "solvent-sniffer" group (n=72, 9 litters). During P2-P21, each animal was exposed daily to either organic solvent vapors (75% toluene and 18% n-hexane, a solvent mixture commonly found in glues and adhesives) or clean air. To determine the impact of early solvent inhalation on cortical neuronal differentiation, brains were stained using the Golgi-Cox-Sholl procedure to quantitatively assess neocortical pyramidal cell dendrogenesis. Preweaning, solvent-exposed animals displayed dramatic impairments in dendritic growth as well as significant reductions in brain weight and size. Copyright 2010 ISDN. Published by Elsevier Ltd. All rights reserved.

Theory of polyelectrolytes in solvents.

PubMed

Chitanvis, Shirish M

2003-12-01

Using a continuum description, we account for fluctuations in the ionic solvent surrounding a Gaussian, charged chain and derive an effective short-ranged potential between the charges on the chain. This potential is repulsive at short separations and attractive at longer distances. The chemical potential can be derived from this potential. When the chemical potential is positive, it leads to a meltlike state. For a vanishingly low concentration of segments, this state exhibits scaling behavior for long chains. The Flory exponent characterizing the radius of gyration for long chains is calculated to be approximately 0.63, close to the classical value obtained for second order phase transitions. For short chains, the radius of gyration varies linearly with N, the chain length, and is sensitive to the parameters in the interaction potential. The linear dependence on the chain length N indicates a stiff behavior. The chemical potential associated with this interaction changes sign, when the screening length in the ionic solvent exceeds a critical value. This leads to condensation when the chemical potential is negative. In this state, it is shown using the mean-field approximation that spherical and toroidal condensed shapes can be obtained. The thickness of the toroidal polyelectrolyte is studied as a function of the parameters of the model, such as the ionic screening length. The predictions of this theory should be amenable to experimental verification.

A Markov Random Field Framework for Protein Side-Chain Resonance Assignment

NASA Astrophysics Data System (ADS)

Zeng, Jianyang; Zhou, Pei; Donald, Bruce Randall

Nuclear magnetic resonance (NMR) spectroscopy plays a critical role in structural genomics, and serves as a primary tool for determining protein structures, dynamics and interactions in physiologically-relevant solution conditions. The current speed of protein structure determination via NMR is limited by the lengthy time required in resonance assignment, which maps spectral peaks to specific atoms and residues in the primary sequence. Although numerous algorithms have been developed to address the backbone resonance assignment problem [68,2,10,37,14,64,1,31,60], little work has been done to automate side-chain resonance assignment [43, 48, 5]. Most previous attempts in assigning side-chain resonances depend on a set of NMR experiments that record through-bond interactions with side-chain protons for each residue. Unfortunately, these NMR experiments have low sensitivity and limited performance on large proteins, which makes it difficult to obtain enough side-chain resonance assignments. On the other hand, it is essential to obtain almost all of the side-chain resonance assignments as a prerequisite for high-resolution structure determination. To overcome this deficiency, we present a novel side-chain resonance assignment algorithm based on alternative NMR experiments measuring through-space interactions between protons in the protein, which also provide crucial distance restraints and are normally required in high-resolution structure determination. We cast the side-chain resonance assignment problem into a Markov Random Field (MRF) framework, and extend and apply combinatorial protein design algorithms to compute the optimal solution that best interprets the NMR data. Our MRF framework captures the contact map information of the protein derived from NMR spectra, and exploits the structural information available from the backbone conformations determined by orientational restraints and a set of discretized side-chain conformations (i.e., rotamers). A Hausdorff-based computation is employed in the scoring function to evaluate the probability of side-chain resonance assignments to generate the observed NMR spectra. The complexity of the assignment problem is first reduced by using a dead-end elimination (DEE) algorithm, which prunes side-chain resonance assignments that are provably not part of the optimal solution. Then an A* search algorithm is used to find a set of optimal side-chain resonance assignments that best fit the NMR data. We have tested our algorithm on NMR data for five proteins, including the FF Domain 2 of human transcription elongation factor CA150 (FF2), the B1 domain of Protein G (GB1), human ubiquitin, the ubiquitin-binding zinc finger domain of the human Y-family DNA polymerase Eta (pol η UBZ), and the human Set2-Rpb1 interacting domain (hSRI). Our algorithm assigns resonances for more than 90% of the protons in the proteins, and achieves about 80% correct side-chain resonance assignments. The final structures computed using distance restraints resulting from the set of assigned side-chain resonances have backbone RMSD 0.5 - 1.4 Å and all-heavy-atom RMSD 1.0 - 2.2 Å from the reference structures that were determined by X-ray crystallography or traditional NMR approaches. These results demonstrate that our algorithm can be successfully applied to automate side-chain resonance assignment and high-quality protein structure determination. Since our algorithm does not require any specific NMR experiments for measuring the through-bond interactions with side-chain protons, it can save a significant amount of both experimental cost and spectrometer time, and hence accelerate the NMR structure determination process.

Thermal stability study of a new guanidine suppressor for the next-generation caustic-side solvent extraction process

DOE PAGES

Hill, Talon G.; Ensor, Dale D.; Delmau, Lætitia Helene; ...

2016-02-06

Cesium stripping performance of thermally stressed solvent degrades slowly over time in batch tests of the Next Generation Caustic-Side Solvent Extraction (NGS) process. NGS is currently used at pilot scale at the Savannah River Site for the selective removal of cesium from high-level salt waste. Recently a new guanidine, N,N',N" -tris(3,7-dimethyloctyl)guanidine (TiDG), was chosen for use as the suppressor, a lipophilic organic base needed for stripping, and the present study was undertaken to address the question of its stability. The NGS process solvent was evaluated for a period of three months under a variety of temperature and storage conditions. Themore » performance of the solvent was tested at 30-day increments using a standard extraction, scrub, strip, and extraction (ES 2S 3E) sequence. Lastly, the results provide insight on the effects of storage and process conditions, the stripping behavior of TiDG, and the stability of the new solvent composition.« less

Thermal stability study of a new guanidine suppressor for the next-generation caustic-side solvent extraction process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hill, Talon G.; Ensor, Dale D.; Delmau, Lætitia Helene

Cesium stripping performance of thermally stressed solvent degrades slowly over time in batch tests of the Next Generation Caustic-Side Solvent Extraction (NGS) process. NGS is currently used at pilot scale at the Savannah River Site for the selective removal of cesium from high-level salt waste. Recently a new guanidine, N,N',N" -tris(3,7-dimethyloctyl)guanidine (TiDG), was chosen for use as the suppressor, a lipophilic organic base needed for stripping, and the present study was undertaken to address the question of its stability. The NGS process solvent was evaluated for a period of three months under a variety of temperature and storage conditions. Themore » performance of the solvent was tested at 30-day increments using a standard extraction, scrub, strip, and extraction (ES 2S 3E) sequence. Lastly, the results provide insight on the effects of storage and process conditions, the stripping behavior of TiDG, and the stability of the new solvent composition.« less

How the extra methylene group affects the ligation properties of Glu vs. Asp and Gln vs. Asn amino acids: a DFT/PCM study.

PubMed

Dudev, Todor; Doudeva, Lyudmila

2017-02-01

The effect of the extra methylene group on the ligation properties of glutamic (Glu) vs. aspartic (Asp) acid, and glutamine (Gln) vs. asparagine (Asn) amino acids-two pairs of protein building blocks differing by the length of their side chains-has been studied by employing DFT calculations combined with polarizable continuum model (PCM) computations. Complexes of the nominal species with partner ligands of various structures, charge states, and degree of solvent exposure have been examined. The results obtained reveal that the difference in the alkyl chain length of these amino acid residues does not affect the mode of their binding. This, however, influences the thermodynamics of the ligand-ligand and ligand-metal recognition thus bestowing unique ligation characteristics on the competing entities. The calculations reveal that the competition between the longer-chain and shorter-chain analogs is entropy driven and that the differential electronic effects are of minor importance for the process. Thus, the outcome of the rivalry between Asp and Glu, and Asn and Gln is almost unaffected by the nature of the partner ligand, its charge state and, in most cases, the dielectric properties of the binding site. The longer-chain Glu, as opposed to its shorter-chain Asp counterpart, is the preferred partner ligand in various protein binding sites. Contrariwise, the shorter-chain Asn binds more favorably to the respective binding sites than its longer-chain Gln analog. The results obtained shed additional light on the intimate mechanism of the ligand-ligand and ligand-metal recognition in proteins and could be employed as guidelines in protein engineering and design.

Antibody side chain conformations are position-dependent.

PubMed

Leem, Jinwoo; Georges, Guy; Shi, Jiye; Deane, Charlotte M

2018-04-01

Side chain prediction is an integral component of computational antibody design and structure prediction. Current antibody modelling tools use backbone-dependent rotamer libraries with conformations taken from general proteins. Here we present our antibody-specific rotamer library, where rotamers are binned according to their immunogenetics (IMGT) position, rather than their local backbone geometry. We find that for some amino acid types at certain positions, only a restricted number of side chain conformations are ever observed. Using this information, we are able to reduce the breadth of the rotamer sampling space. Based on our rotamer library, we built a side chain predictor, position-dependent antibody rotamer swapper (PEARS). On a blind test set of 95 antibody model structures, PEARS had the highest average χ 1 and χ1+2 accuracy (78.7% and 64.8%) compared to three leading backbone-dependent side chain predictors. Our use of IMGT position, rather than backbone ϕ/ψ, meant that PEARS was more robust to errors in the backbone of the model structure. PEARS also achieved the lowest number of side chain-side chain clashes. PEARS is freely available as a web application at http://opig.stats.ox.ac.uk/webapps/pears. © 2018 Wiley Periodicals, Inc.

Cleavable ester linked magnetic nanoparticles for labeling of solvent exposed primary amine groups of peptides/proteins

USDA-ARS?s Scientific Manuscript database

In order to study the solvent exposed lysine residues of peptides/proteins, we previously reported disulfide linked N-hydrosuccinimide ester modified silica coated iron oxide magnetic nanoparticles (NHS-SS-SiO2@Fe3O4 MNPs). The presence of a disulfide bond in the linker limits the use of disulfide r...

Electrohydrodynamics in nanochannels coated by mixed polymer brushes: effects of electric field strength and solvent quality

NASA Astrophysics Data System (ADS)

Cao, Qianqian; Tian, Xiu; You, Hao

2018-04-01

We examine the electrohydrodynamics in mixed polymer brush-coated nanochannels and the conformational dynamics of grafted polymers using molecular dynamics simulations. Charged (A) and neutral polymers (B) are alternately grafted on the channel surfaces. The effects of the electric field strength and solvent quality are addressed in detail. The dependence of electroosmotic flow characteristics and polymer conformational behavior on the solvent quality is influenced due to the change of the electric field strength. The enhanced electric field induces a collapse of the neutral polymer chains which adopt a highly extended conformation along the flow direction. However, the thickness of the charged polymer layer is affected weakly by the electric field, and even a slight swelling is identified for the A-B attraction case, implying the conformational coupling between two polymer species. Furthermore, the charged polymer chains incline entirely towards the electric field direction oppositely to the flow direction. More importantly, unlike the neutral polymer chains, the shape factor of the charged polymer chains, which is used to describe the overall shape of polymer chains, is reduced significantly with increasing the electric field strength, corresponding to a more coiled structure.

Evaluation of the utility of a standard history questionnaire in assessing the neurological effects of solvents.

PubMed

Bukowski, J A; Sargent, E V; Pena, B M

1992-01-01

Using a standard battery of medical surveillance questions, a study was undertaken to determine if an increase in reported neurologic symptoms was resulting from solvent exposure at a pharmaceutical research, development, and manufacturing site. The prevalence of positive responses to 13 interval history questions pertaining to neurological symptoms was compared between those enrolled in exposed surveillance programs (n = 840) and those enrolled in other, non-solvent exposed surveillance programs (n = 1,042). The ratio of positive responders between the exposed and unexposed groups was used to generate a relative prevalence ratio (RPR). No significantly elevated RPRs were seen when the analysis was adjusted for the confounding factors of age, sex, smoking, alcohol use, noise exposure, and number of interval histories. These results suggest that workplace solvent exposures in the employees studied did not appear to result in obvious neurologic symptoms. However, low-level neurotoxic exposures can cause asymptomatic or sub-clinical disorders. Therefore, more sensitive neurotoxic surveillance systems need to be developed.

Influence of Protein Scaffold on Side-Chain Transfer Free Energies.

PubMed

Marx, Dagen C; Fleming, Karen G

2017-08-08

The process by which membrane proteins fold involves the burial of side chains into lipid bilayers. Both structure and function of membrane proteins depend on the magnitudes of side-chain transfer free energies (ΔΔG sc o ). In the absence of other interactions, ΔΔG sc o is an independent property describing the energetics of an isolated side chain in the bilayer. However, in reality, side chains are attached to the peptide backbone and surrounded by other side chains in the protein scaffold in biology, which may alter the apparent ΔΔG sc o . Previously we reported a whole protein water-to-bilayer hydrophobicity scale using the transmembrane β-barrel Escherichia coli OmpLA as a scaffold protein. To investigate how a different protein scaffold can modulate these energies, we measured ΔΔG sc o for all 20 amino acids using the transmembrane β-barrel E. coli PagP as a scaffold protein. This study represents, to our knowledge, the first instance of ΔΔG sc o measured in the same experimental conditions in two structurally and sequentially distinct protein scaffolds. Although the two hydrophobicity scales are strongly linearly correlated, we find that there are apparent scaffold induced changes in ΔΔG sc o for more than half of the side chains, most of which are polar residues. We propose that the protein scaffold affects the ΔΔG sc o of side chains that are buried in unfavorable environments by dictating the mechanisms by which the side chain can reach a more favorable environment and thus modulating the magnitude of ΔΔG sc o . Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

A Solid-State Deuterium NMR and SFG Study of the Side Chain Dynamics of Peptides Adsorbed onto Surfaces

PubMed Central

Breen, Nicholas F.; Weidner, Tobias; Li, Kun; Castner, David G.; Drobny, Gary P.

2011-01-01

The artificial amphiphilic peptide LKα14 adopts a helical structure at interfaces, with opposite orientation of its leucine (L, hydrophobic) and lysine (K, hydrophilic) side chains. When adsorbed onto surfaces, different residue side chains necessarily have different proximities to the surface, depending on both their position in the helix and the composition of the surface itself. Deuterating the individual leucine residues (isopropyl-d7) permits the use of solid-state deuterium NMR as a site-specific probe of side chain dynamics. In conjunction with SFG as a probe of the peptide binding face, we demonstrate that the mobility of specific leucine side chains at the interface is quantifiable in terms of their surface proximity. PMID:19764755

Unique aspects of the structure and dynamics of elementary Iβ cellulose microfibrils revealed by computational simulations.

PubMed

Oehme, Daniel P; Downton, Matthew T; Doblin, Monika S; Wagner, John; Gidley, Michael J; Bacic, Antony

2015-05-01

The question of how many chains an elementary cellulose microfibril contains is critical to understanding the molecular mechanism(s) of cellulose biosynthesis and regulation. Given the hexagonal nature of the cellulose synthase rosette, it is assumed that the number of chains must be a multiple of six. We present molecular dynamics simulations on three different models of Iβ cellulose microfibrils, 18, 24, and 36 chains, to investigate their structure and dynamics in a hydrated environment. The 36-chain model stays in a conformational space that is very similar to the initial crystalline phase, while the 18- and 24-chain models sample a conformational space different from the crystalline structure yet similar to conformations observed in recent high-temperature molecular dynamics simulations. Major differences in the conformations sampled between the different models result from changes to the tilt of chains in different layers, specifically a second stage of tilt, increased rotation about the O2-C2 dihedral, and a greater sampling of non-TG exocyclic conformations, particularly the GG conformation in center layers and GT conformation in solvent-exposed exocyclic groups. With a reinterpretation of nuclear magnetic resonance data, specifically for contributions made to the C6 peak, data from the simulations suggest that the 18- and 24-chain structures are more viable models for an elementary cellulose microfibril, which also correlates with recent scattering and diffraction experimental data. These data inform biochemical and molecular studies that must explain how a six-particle cellulose synthase complex rosette synthesizes microfibrils likely comprised of either 18 or 24 chains. © 2015 American Society of Plant Biologists. All Rights Reserved.

Electrolyte with Low Polysulfide Solubility for Li-S Batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Ke; Wu, Qin; Tong, Xiao

Here, Li-S battery is one of the most promising next generation rechargeable battery technologies due to its high theoretical energy density and low material cost. While its success is impeded by the low energy efficiency and fast capacity fade primarily caused by the discharge intermediates, Li-polysulfides (PS), dissolution in the electrolyte. Mitigation of PS dissolution in electrolyte involves the search of new electrolyte solvent system that exhibits poor solvation to the PS while still have good solvation ability to the electrolyte salt for high ionic conductivity. Applying co-solvents with reduced solvating power but compatible with the state of art Li-Smore » battery’s ether-based electrolyte is one of the most promising concepts. This route is also advantageous of having a low scale-up cost. With the aids of Quantum Chemical Calculation, we have identified high carbon-to-oxygen (C/O) ratio ethers as co-solvent in the new electrolytes that effectively impede PS dissolution while still maintaining high ionic conductivity. Significantly improved cycle life and cycling Coulombic efficiency are observed for Li-S cells using the new composite electrolytes. Anode analysis with different methods also demonstrate that reducing electrolyte’s PS solubility results in less sulfur total amount on the lithium anode surface and lower ratio of the longer-chain PS, which is probably a sign of suppressed side reactions between the anode and PS in the electrolyte.« less

Electrolyte with Low Polysulfide Solubility for Li-S Batteries

DOE PAGES

Sun, Ke; Wu, Qin; Tong, Xiao; ...

2018-05-23

Here, Li-S battery is one of the most promising next generation rechargeable battery technologies due to its high theoretical energy density and low material cost. While its success is impeded by the low energy efficiency and fast capacity fade primarily caused by the discharge intermediates, Li-polysulfides (PS), dissolution in the electrolyte. Mitigation of PS dissolution in electrolyte involves the search of new electrolyte solvent system that exhibits poor solvation to the PS while still have good solvation ability to the electrolyte salt for high ionic conductivity. Applying co-solvents with reduced solvating power but compatible with the state of art Li-Smore » battery’s ether-based electrolyte is one of the most promising concepts. This route is also advantageous of having a low scale-up cost. With the aids of Quantum Chemical Calculation, we have identified high carbon-to-oxygen (C/O) ratio ethers as co-solvent in the new electrolytes that effectively impede PS dissolution while still maintaining high ionic conductivity. Significantly improved cycle life and cycling Coulombic efficiency are observed for Li-S cells using the new composite electrolytes. Anode analysis with different methods also demonstrate that reducing electrolyte’s PS solubility results in less sulfur total amount on the lithium anode surface and lower ratio of the longer-chain PS, which is probably a sign of suppressed side reactions between the anode and PS in the electrolyte.« less

Crystal structure of triosephosphate isomerase from Trypanosoma cruzi in hexane

PubMed Central

Gao, Xiu-Gong; Maldonado, Ernesto; Pérez-Montfort, Ruy; Garza-Ramos, Georgina; de Gómez-Puyou, Marietta Tuena; Gómez-Puyou, Armando; Rodríguez-Romero, Adela

1999-01-01

To gain insight into the mechanisms of enzyme catalysis in organic solvents, the x-ray structure of some monomeric enzymes in organic solvents was determined. However, it remained to be explored whether the structure of oligomeric proteins is also amenable to such analysis. The field acquired new perspectives when it was proposed that the x-ray structure of enzymes in nonaqueous media could reveal binding sites for organic solvents that in principle could represent the starting point for drug design. Here, a crystal of the dimeric enzyme triosephosphate isomerase from the pathogenic parasite Trypanosoma cruzi was soaked and diffracted in hexane and its structure solved at 2-Å resolution. Its overall structure and the dimer interface were not altered by hexane. However, there were differences in the orientation of the side chains of several amino acids, including that of the catalytic Glu-168 in one of the monomers. No hexane molecules were detected in the active site or in the dimer interface. However, three hexane molecules were identified on the surface of the protein at sites, which in the native crystal did not have water molecules. The number of water molecules in the hexane structure was higher than in the native crystal. Two hexanes localized at <4 Å from residues that form the dimer interface; they were in close proximity to a site that has been considered a potential target for drug design. PMID:10468562

Crystal structure of triosephosphate isomerase from Trypanosoma cruzi in hexane.

PubMed

Gao, X G; Maldonado, E; Pérez-Montfort, R; Garza-Ramos, G; de Gómez-Puyou, M T; Gómez-Puyou, A; Rodríguez-Romero, A

1999-08-31

To gain insight into the mechanisms of enzyme catalysis in organic solvents, the x-ray structure of some monomeric enzymes in organic solvents was determined. However, it remained to be explored whether the structure of oligomeric proteins is also amenable to such analysis. The field acquired new perspectives when it was proposed that the x-ray structure of enzymes in nonaqueous media could reveal binding sites for organic solvents that in principle could represent the starting point for drug design. Here, a crystal of the dimeric enzyme triosephosphate isomerase from the pathogenic parasite Trypanosoma cruzi was soaked and diffracted in hexane and its structure solved at 2-A resolution. Its overall structure and the dimer interface were not altered by hexane. However, there were differences in the orientation of the side chains of several amino acids, including that of the catalytic Glu-168 in one of the monomers. No hexane molecules were detected in the active site or in the dimer interface. However, three hexane molecules were identified on the surface of the protein at sites, which in the native crystal did not have water molecules. The number of water molecules in the hexane structure was higher than in the native crystal. Two hexanes localized at <4 A from residues that form the dimer interface; they were in close proximity to a site that has been considered a potential target for drug design.

[Exposure to solvents and tardy epilepsy: 2 clinical cases].

PubMed

Bernardini, P; Scoppetta, C

1992-01-01

Organic solvents (OS) are widely used in industry and craft work. The neurotoxic effects of OS are well known in occupational exposure occurring in poor industrial hygiene conditions. There has been interest recently in a possible epileptogenic effect of OS exposure. Two cases are reported of late onset epilepsy observed in workers heavily exposed to OS. Case 1 was a 27-year-old male painter employed in a car body repair workshop. Solvent exposure was high for a few months because after his regular work, the man continued working as a car body painter in his own private concern. After a period of weakness and headache, probably indicating an excessive solvent absorption, he suffered two generalized paroxysmal seizures during sleep which necessitated hospitalization and continuous treatment with barbiturates. Case 2 was a 44-year-old male painter in a road advertising billboard factory who was continuously exposed to OS. Ten years previously he had been exposed to accidental massive inhalation of solvent vapours while opening a drum of solvents for coloured paint. Acute solvent poisoning followed and seven weeks later he suffered several epileptic episodes associated with typical EEG alterations; for many years, however, treatment was ineffective. In both cases there was neither a history of neurologic disease nor any other neurologic dysfunctions and the results of comprehensive neuroradiological studies were normal. Evidence exists of a chronological connection between high exposure to paint solvents and clinical evidence of late onset epilepsy, but it is not possible to identify a definite causal relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of Protein Side-Chain Conformation Prediction Methods in Different Residue Environments

PubMed Central

Peterson, Lenna X.; Kang, Xuejiao; Kihara, Daisuke

2016-01-01

Computational prediction of side-chain conformation is an important component of protein structure prediction. Accurate side-chain prediction is crucial for practical applications of protein structure models that need atomic detailed resolution such as protein and ligand design. We evaluated the accuracy of eight side-chain prediction methods in reproducing the side-chain conformations of experimentally solved structures deposited to the Protein Data Bank. Prediction accuracy was evaluated for a total of four different structural environments (buried, surface, interface, and membrane-spanning) in three different protein types (monomeric, multimeric, and membrane). Overall, the highest accuracy was observed for buried residues in monomeric and multimeric proteins. Notably, side-chains at protein interfaces and membrane-spanning regions were better predicted than surface residues even though the methods did not all use multimeric and membrane proteins for training. Thus, we conclude that the current methods are as practically useful for modeling protein docking interfaces and membrane-spanning regions as for modeling monomers. PMID:24619909

Structurally conserved water molecules in ribonuclease T1.

PubMed

Malin, R; Zielenkiewicz, P; Saenger, W

1991-03-15

In the high resolution (1.7-1.9 A) crystal structures of ribonuclease T1 (RNase T1) in complex with guanosine, guanosine 2'-phosphate, guanylyl 2',5'-guanosine, and vanadate, there are 30 water sites in nearly identical (+/- 1 A) positions that are considered conserved. One water is tightly bound to Asp76(O delta), Thr93(O gamma), Cys6(O), and Asn9(N); another bridges two loops by hydrogen-bonding to Tyr68(O eta) and to Ser35(N), Asn36(N); a loop structure is stabilized by two waters coordinated to Gly31(O) and His27(N delta), and by water bound to cis-Pro39(O). Most notable is a hydrogen-bonded chain of 10 water molecules. Waters 1-5 of this chain are inaccessible to solvent, are anchored at Trp59(N), and stitch together the loop formed by segments 60-68; waters 5-8 coordinate to Ca2+, and waters 9 and 10 hydrogen-bond to N-terminal side chains of the alpha-helix. The water chain and two conserved water molecules are bound to amino acids adjacent to the active site residues His40, Glu58, Arg77, and His92; they are probably involved in maintaining their spatial orientation required for catalysis. Water sites must be considered in genetic engineering; the mutation Trp59Tyr, which probably influences the 10-water chain, doubles the catalytic activity of RNase T1.

SAMPL5: 3D-RISM partition coefficient calculations with partial molar volume corrections and solute conformational sampling.

PubMed

Luchko, Tyler; Blinov, Nikolay; Limon, Garrett C; Joyce, Kevin P; Kovalenko, Andriy

2016-11-01

Implicit solvent methods for classical molecular modeling are frequently used to provide fast, physics-based hydration free energies of macromolecules. Less commonly considered is the transferability of these methods to other solvents. The Statistical Assessment of Modeling of Proteins and Ligands 5 (SAMPL5) distribution coefficient dataset and the accompanying explicit solvent partition coefficient reference calculations provide a direct test of solvent model transferability. Here we use the 3D reference interaction site model (3D-RISM) statistical-mechanical solvation theory, with a well tested water model and a new united atom cyclohexane model, to calculate partition coefficients for the SAMPL5 dataset. The cyclohexane model performed well in training and testing ([Formula: see text] for amino acid neutral side chain analogues) but only if a parameterized solvation free energy correction was used. In contrast, the same protocol, using single solute conformations, performed poorly on the SAMPL5 dataset, obtaining [Formula: see text] compared to the reference partition coefficients, likely due to the much larger solute sizes. Including solute conformational sampling through molecular dynamics coupled with 3D-RISM (MD/3D-RISM) improved agreement with the reference calculation to [Formula: see text]. Since our initial calculations only considered partition coefficients and not distribution coefficients, solute sampling provided little benefit comparing against experiment, where ionized and tautomer states are more important. Applying a simple [Formula: see text] correction improved agreement with experiment from [Formula: see text] to [Formula: see text], despite a small number of outliers. Better agreement is possible by accounting for tautomers and improving the ionization correction.

SAMPL5: 3D-RISM partition coefficient calculations with partial molar volume corrections and solute conformational sampling

NASA Astrophysics Data System (ADS)

Luchko, Tyler; Blinov, Nikolay; Limon, Garrett C.; Joyce, Kevin P.; Kovalenko, Andriy

2016-11-01

Implicit solvent methods for classical molecular modeling are frequently used to provide fast, physics-based hydration free energies of macromolecules. Less commonly considered is the transferability of these methods to other solvents. The Statistical Assessment of Modeling of Proteins and Ligands 5 (SAMPL5) distribution coefficient dataset and the accompanying explicit solvent partition coefficient reference calculations provide a direct test of solvent model transferability. Here we use the 3D reference interaction site model (3D-RISM) statistical-mechanical solvation theory, with a well tested water model and a new united atom cyclohexane model, to calculate partition coefficients for the SAMPL5 dataset. The cyclohexane model performed well in training and testing (R=0.98 for amino acid neutral side chain analogues) but only if a parameterized solvation free energy correction was used. In contrast, the same protocol, using single solute conformations, performed poorly on the SAMPL5 dataset, obtaining R=0.73 compared to the reference partition coefficients, likely due to the much larger solute sizes. Including solute conformational sampling through molecular dynamics coupled with 3D-RISM (MD/3D-RISM) improved agreement with the reference calculation to R=0.93. Since our initial calculations only considered partition coefficients and not distribution coefficients, solute sampling provided little benefit comparing against experiment, where ionized and tautomer states are more important. Applying a simple pK_{ {a}} correction improved agreement with experiment from R=0.54 to R=0.66, despite a small number of outliers. Better agreement is possible by accounting for tautomers and improving the ionization correction.

Phase separation of comb polymer nanocomposite melts.

PubMed

Xu, Qinzhi; Feng, Yancong; Chen, Lan

2016-02-07

In this work, the spinodal phase demixing of branched comb polymer nanocomposite (PNC) melts is systematically investigated using the polymer reference interaction site model (PRISM) theory. To verify the reliability of the present method in characterizing the phase behavior of comb PNCs, the intermolecular correlation functions of the system for nonzero particle volume fractions are compared with our molecular dynamics simulation data. After verifying the model and discussing the structure of the comb PNCs in the dilute nanoparticle limit, the interference among the side chain number, side chain length, nanoparticle-monomer size ratio and attractive interactions between the comb polymer and nanoparticles in spinodal demixing curves is analyzed and discussed in detail. The results predict two kinds of distinct phase separation behaviors. One is called classic fluid phase boundary, which is mediated by the entropic depletion attraction and contact aggregation of nanoparticles at relatively low nanoparticle-monomer attraction strength. The second demixing transition occurs at relatively high attraction strength and involves the formation of an equilibrium physical network phase with local bridging of nanoparticles. The phase boundaries are found to be sensitive to the side chain number, side chain length, nanoparticle-monomer size ratio and attractive interactions. As the side chain length is fixed, the side chain number has a large effect on the phase behavior of comb PNCs; with increasing side chain number, the miscibility window first widens and then shrinks. When the side chain number is lower than a threshold value, the phase boundaries undergo a process from enlarging the miscibility window to narrowing as side chain length increases. Once the side chain number overtakes this threshold value, the phase boundary shifts towards less miscibility. With increasing nanoparticle-monomer size ratio, a crossover of particle size occurs, above which the phase separation is consistent with that of chain PNCs. The miscibility window for this condition gradually narrows while the other parameters of the PNCs system are held constant. These results indicate that the present PRISM theory can give molecular-level details of the underlying mechanisms of the comb PNCs. It is hoped that the results can be used to provide useful guidance for the future design control of novel, thermodynamically stable comb PNCs.

Photolysis of nonylphenol ethoxylates: the determination of the degradation kinetics and the intermediate products.

PubMed

Chen, Ling; Zhou, Hai-Yun; Deng, Qin-Ying

2007-06-01

The photolysis of nonylphenol ethoxylates with an average oligomers length of ten ethoxylate units (NPEO(10)) in aqueous solution under UV, as well as the influence of humic acid (HA) on the photolysis was studied. A 125W high-pressure mercury lamp was employed as the light source. The intermediate products from the photolysis were determined by LC-MS. The results indicated that NPEO(10) underwent direct photolysis upon exposed to UV. The degradation pathway was complex. Besides the generally proposed degradation pathway of ethylene oxide (EO) side chains shortening, the oxidation of alkyl chain and EO chain led to intermediates having both a carboxylated (as well as carbonylated) ethoxylate and alkyl chain of varying lengths. The hydrogenation of benzene ring was also detected. The kinetics data showed that the first order reaction kinetics could be well used to describe the kinetics of NPEO(10) degradation. In the presence of dissolved organic matter by HA addition, the performance of NPEO(10) photodegradation was reduced. The photolysis rate decreased with increased HA concentration.

Effect of chain stiffness on the structure of single-chain polymer nanoparticles

NASA Astrophysics Data System (ADS)

Moreno, Angel J.; Bacova, Petra; Lo Verso, Federica; Arbe, Arantxa; Colmenero, Juan; Pomposo, José A.

2018-01-01

Polymeric single-chain nanoparticles (SCNPs) are soft nano-objects synthesized by purely intramolecular cross-linking of single polymer chains. By means of computer simulations, we investigate the conformational properties of SCNPs as a function of the bending stiffness of their linear polymer precursors. We investigate a broad range of characteristic ratios from the fully flexible case to those typical of bulky synthetic polymers. Increasing stiffness hinders bonding of groups separated by short contour distances and increases looping over longer distances, leading to more compact nanoparticles with a structure of highly interconnected loops. This feature is reflected in a crossover in the scaling behaviour of several structural observables. The scaling exponents change from those characteristic for Gaussian chains or rings in θ-solvents in the fully flexible limit, to values resembling fractal or ‘crumpled’ globular behaviour for very stiff SCNPs. We characterize domains in the SCNPs. These are weakly deformable regions that can be seen as disordered analogues of domains in disordered proteins. Increasing stiffness leads to bigger and less deformable domains. Surprisingly, the scaling behaviour of the domains is in all cases similar to that of Gaussian chains or rings, irrespective of the stiffness and degree of cross-linking. It is the spatial arrangement of the domains which determines the global structure of the SCNP (sparse Gaussian-like object or crumpled globule). Since intramolecular stiffness can be varied through the specific chemistry of the precursor or by introducing bulky side groups in its backbone, our results propose a new strategy to tune the global structure of SCNPs.

Precise structural analysis of α-helical polypeptide by quantum-chemical calculation related to reciprocal side-chain combination of two L-phenylalanine residues

NASA Astrophysics Data System (ADS)

Niimura, Subaru; Kurosu, Hiromichi; Shoji, Akira

2010-04-01

To clarify the positive role of side-chain conformation in the stability of protein secondary structure (main-chain conformation), we successfully calculated the optimization structure of a series of well-defined α-helical octadecapeptides composed of two L-phenylalanine (Phe) and 16 L-alanine (Ala) residues, based on the molecular orbital calculation with density functional theory (DFT/B3LYP/6-31G(d)). From the total energy calculation and the precise secondary structural analysis, we found that the conformational stability of the α-helix is closely related to the reciprocal side-chain combinations (such as positional relation and side-chain conformation) of two Phe residues in this system. Furthermore, we demonstrated that the 1H, 13C, 15N and 17O isotropic chemical shifts of each Phe residue depend on the respective side-chain conformations of the Phe residue.

Method And Apparatus For Production Of Bi-213 From The Activity Ac-225 Source

DOEpatents

Egorov, Oleg B.; O'Hara, Matthew J.

2005-12-06

A method and apparatus for isolating and purifying a .sup.213 Bi radioactive isotope from an .sup.225 Ac source using a primary column and a primary sorbent which preferentially retains .sup.225 Ac over .sup.213 Bi when exposed to a compatible solvent in combination with a secondary column having a secondary sorbent which retains .sup.213 Bi when exposed to a mixture of the compatible solvent and .sup.213 Bi. A "compatible solvent" is a solvent which will preferentially remove .sup.213 Bi radioactive isotopes from a primary sorbent without removing .sup.225 Ac radioactive isotopes, and then allow .sup.213 Bi radioactive isotopes removed from the primary sorbent to be retained on a secondary sorbent, without having to dilute or otherwise chemically or physically modify the compatible solvent in between exposure to the primary and secondary sorbents.

Solution structure of a small protein containing a fluorinated side chain in the core

PubMed Central

Cornilescu, Gabriel; Hadley, Erik B.; Woll, Matthew G.; Markley, John L.; Gellman, Samuel H.; Cornilescu, Claudia C.

2007-01-01

We report the first high-resolution structure for a protein containing a fluorinated side chain. Recently we carried out a systematic evaluation of phenylalanine to pentafluorophenylalanine (Phe → F5-Phe) mutants for the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe → F5-Phe mutations are interesting because aryl–perfluoroaryl interactions of optimal geometry are intrinsically more favorable than either aryl–aryl or perfluoroaryl–perfluoroaryl interactions, and because perfluoroaryl units are more hydrophobic than are analogous aryl units. Only one mutation, Phe10 → F5-Phe, was found to provide enhanced tertiary structural stability relative to the native core (by ∼1 kcal/mol, according to guanidinium chloride denaturation studies). The NMR structure of this mutant, described here, reveals very little variation in backbone conformation or side chain packing relative to the wild type. Thus, although Phe → F5-Phe mutations offer the possibility of greater tertiary structural stability from side chain–side chain attraction and/or side chain desolvation, the constraints associated with the native c-VHP fold apparently prevent the modified polypeptide from taking advantage of this possibility. Our findings are important because they complement several studies that have shown that fluorination of saturated side chain carbon atoms can provide enhanced conformational stability. PMID:17123960

Reversible switch between the nanoporous and the nonporous state of amphiphilic block copolymer films regulated by selective swelling.

PubMed

Yan, Nina; Wang, Yong

2015-09-21

Switchable nanoporous films, which can repeatedly alternate their porosities, are of great interest in a diversity of fields. Currently these intelligent materials are mostly based on polyelectrolytes and their porosities can change only in relatively narrow ranges, typically under wet conditions, severely limiting their applications. Here we develop a new system, which is capable of reversibly switching between a highly porous state and a nonporous state dozens of times regulated simply by exposure to selective solvents. In this system nanopores are created or reversibly eliminated in films of a block copolymer, polystyrene-block-poly(2-vinyl pyridine) (PS-b-P2VP), by exposing the films to P2VP-selective or PS-selective solvents, respectively. The mechanism of the switch is based on the selective swelling of the constituent blocks in corresponding solvents, which is a nondestructive and easily controllable process enabling the repeatable and ample switch between the open and the closed state. Systematic microscopic and ellipsometric characterization methods are performed to elucidate the pore-closing course induced by nonsolvents and the cycling between the pore-open and the pore-closed state up to 20 times. The affinity of the solvent for PS blocks is found to play a dominating role in determining the pore-closing process and the porosities of the pore-open films increase with the cycling numbers as a result of loose packing conditions of the polymer chains. We finally demonstrate the potential applications of these films as intelligent antireflection coatings and drug carriers.

Next Generation Solvent (NGS): Development for Caustic-Side Solvent Extraction of Cesium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moyer, Bruce A.; Birdwell, Jr, Joseph F.; Bonnesen, Peter V.

This report summarizes the FY 2010 and 2011 accomplishments at Oak Ridge National Laboratory (ORNL) in developing the Next Generation Caustic-Side Solvent Extraction (NG-CSSX) process, referred to commonly as the Next Generation Solvent (NGS), under funding from the U.S. Department of Energy, Office of Environmental Management (DOE-EM), Office of Technology Innovation and Development. The primary product of this effort is a process solvent and preliminary flowsheet capable of meeting a target decontamination factor (DF) of 40,000 for worst-case Savannah River Site (SRS) waste with a concentration factor of 15 or higher in the 18-stage equipment configuration of the SRS Modularmore » Caustic-Side Solvent Extraction Unit (MCU). In addition, the NG-CSSX process may be readily adapted for use in the SRS Salt Waste Processing Facility (SWPF) or in supplemental tank-waste treatment at Hanford upon appropriate solvent or flowsheet modifications. Efforts in FY 2010 focused on developing a solvent composition and process flowsheet for MCU implementation. In FY 2011 accomplishments at ORNL involved a wide array of chemical-development activities and testing up through single-stage hydraulic and mass-transfer tests in 5-cm centrifugal contactors. Under subcontract from ORNL, Argonne National Laboratory (ANL) designed a preliminary flowsheet using ORNL cesium distribution data, and Tennessee Technological University confirmed a chemical model for cesium distribution ratios (DCs) as a function of feed composition. Interlaboratory efforts were coordinated with complementary engineering tests carried out (and reported separately) by personnel at Savannah River National Laboratory (SRNL) and Savannah River Remediation (SRR) with helpful advice by Parsons Engineering and General Atomics on aspects of possible SWPF implementation.« less

Next Generation Solvent Development for Caustic-Side Solvent Extraction of Cesium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moyer, Bruce A.; Birdwell, Joseph F.; Bonnesen, Peter V.

This report summarizes the FY 2010 and 2011 accomplishments at Oak Ridge National Laboratory (ORNL) in developing the Next Generation Caustic-Side Solvent Extraction (NG-CSSX) process, referred to commonly as the Next Generation Solvent (NGS), under funding from the U.S. Department of Energy, Office of Environmental Management (DOE-EM), Office of Technology Innovation and Development. The primary product of this effort is a process solvent and preliminary flowsheet capable of meeting a target decontamination factor (DF) of 40,000 for worst-case Savannah River Site (SRS) waste with a concentration factor of 15 or higher in the 18-stage equipment configuration of the SRS Modularmore » Caustic-Side Solvent Extraction Unit (MCU). In addition, the NG-CSSX process may be readily adapted for use in the SRS Salt Waste Processing Facility (SWPF) or in supplemental tank-waste treatment at Hanford upon appropriate solvent or flowsheet modifications. Efforts in FY 2010 focused on developing a solvent composition and process flowsheet for MCU implementation. In FY 2011 accomplishments at ORNL involved a wide array of chemical-development activities and testing up through single-stage hydraulic and mass-transfer tests in 5-cm centrifugal contactors. Under subcontract from ORNL, Argonne National Laboratory (ANL) designed a preliminary flowsheet using ORNL cesium distribution data, and Tennessee Technological University confirmed a chemical model for cesium distribution ratios (DCs) as a function of feed composition. Inter laboratory efforts were coordinated with complementary engineering tests carried out (and reported separately) by personnel at Savannah River National Laboratory (SRNL) and Savannah River Remediation (SRR) with helpful advice by Parsons Engineering and General Atomics on aspects of possible SWPF implementation.« less

Synthesis and analgesic activity of some side-chain modified anpirtoline derivatives.

PubMed

Rádl, S; Hezky, P; Proska, J; Hejnová, L; Krejcí, I

2000-05-01

New derivatives of anpirtoline and deazaanpirtoline modified in the side chain have been synthesized. The series includes compounds 3 with side-chains containing piperidine or pyrrolidine rings, compounds 4 containing 8-azabicyclo[3.2.1]octane moiety, and compounds 5 having piperazine ring in their side-chains. Their receptor binding profiles (5-HT1A, 5-HT1B) and analgesic activity (hot plate, acetic acid induced writhing) have been studied. Optimized structures (PM3-MOPAC, Alchemy 2000, Tripos Inc.) of the synthesized compounds 3-5 were compared with that of anpirtoline.

Dissecting the total transition state stabilization provided by amino acid side chains at orotidine 5'-monophosphate decarboxylase: a two-part substrate approach.

PubMed

Barnett, Shonoi A; Amyes, Tina L; Wood, Bryant M; Gerlt, John A; Richard, John P

2008-07-29

Kinetic analysis of decarboxylation catalyzed by S154A, Q215A, and S154A/Q215A mutant yeast orotidine 5'-monophosphate decarboxylases with orotidine 5'-monophosphate (OMP) and with a truncated nucleoside substrate (EO) activated by phosphite dianion shows (1) the side chain of Ser-154 stabilizes the transition state through interactions with the pyrimidine rings of OMP or EO, (2) the side chain of Gln-215 interacts with the phosphodianion group of OMP or with phosphite dianion, and (3) the interloop hydrogen bond between the side chains of Ser-154 and Gln-215 orients the amide side chain of Gln-215 to interact with the phosphodianion group of OMP or with phosphite dianion.

The formation of [M-H]+ ions in N-alkyl-substituted thieno[3,4-c]-pyrrole-4,6-dione derivatives during atmospheric pressure photoionization mass spectrometry.

PubMed

Sioud, Salim; Kharbatia, Najeh; Amad, Maan H; Zhu, Zhiyong; Cabanetos, Clement; Lesimple, Alain; Beaujuge, Pierre

2014-11-30

The formation of ions during atmospheric pressure photoionization (APPI) mass spectrometry in the positive mode usually provides radical cations and/or protonated species. Intriguingly, during the analysis of some N-alkyl-substituted thieno[3,4-c]pyrrole-4,6-dione (TPD) derivatives synthesized in our laboratory, unusual [M-H](+) ion peaks were observed. In this work we investigate the formation of [M-H](+) ions observed under APPI conditions. Multiple experimental parameters, including the type of ionization source, the composition of the solvent, the type of dopant, the infusion flow rate, and the length of the alkyl side chain were investigated to determine their effects on the formation of [M-H](+) ions. In addition, a comparison study of the gas-phase tandem mass spectrometric (MS/MS) fragmentation of [M + H](+) vs [M-H](+) ions and computational approaches were used. [M-H](+) ions were observed under APPI conditions. The type of dopant and the length of the alkyl chain affected the formation of these ions. MS/MS fragmentation of [M-H](+) and [M + H](+) ions exhibited completely different patterns. Theoretical calculations revealed that the loss of hydrogen molecules from the [M + H](+) ions is the most favourable condition under which to form [M-H](+) ions. [M-H](+) ions were detected in all the TPD derivatives studied here under the special experimental conditions during APPI, using a halogenated benzene dopant, and TPD containing substituted N-alkyl side chains with a minimum of four carbon atoms. Density functional theory calculations showed that for [M-H](+) ions to be formed under these conditions, the loss of hydrogen molecules from the [M + H](+)  ions is proposed to be necessary. Copyright © 2014 John Wiley & Sons, Ltd.

Modification of Side Chains of Conjugated Molecules and Polymers for Charge Mobility Enhancement and Sensing Functionality.

PubMed

Liu, Zitong; Zhang, Guanxin; Zhang, Deqing

2018-06-19

Organic semiconductors have received increasing attentions in recent years because of their promising applications in various optoelectronic devices. The key performance metric for organic semiconductors is charge carrier mobility, which is governed by the electronic structures of conjugated backbones and intermolecular/interchain π-π interactions and packing in both microscopic and macroscopic levels. For this reason, more efforts have been paid to the design and synthesis of conjugated frameworks for organic semiconductors with high charge mobilities. However, recent studies manifest that appropriate modifications of side chains that are linked to conjugated frameworks can improve the intermolecular/interchain packing order and boost charge mobilities. In this Account, we discuss our research results in context of modification of side chains in organic semiconductors for charge mobility enhancement. These include the following: (i) The lengths of alkyl chains in sulfur-rich thiepin-fused heteroacences can dramatically influence the intermolecular arrangements and orbital overlaps, ushering in different hole mobilities. Inversely, the lamellar stacking modes of alkyl chains in naphthalene diimide (NDI) derivatives with tetrathiafulvalene (TTF) units are affected by the structures of conjugated cores. (ii) The steric hindrances owing to the bulky branching chains can be weakened by partial replacement of the branching alkyl chains with linear ones for diketopyrrolopyrrole (DPP)-based D (donor)-A (acceptor) conjugated polymers. Such modification of side chains makes the polymer backbones more planar and thus interchain packing order and charge mobilities are improved. The incorporation of hydrophilic tri(ethylene glycol) (TEG) chains into the polymers also leads to improved interchain packing order. In particular, the polymer in which TEG side chains are distributed uniformly exhibits relatively high charge mobility without thermal annealing. (iii) The incorporation of urea groups in the side chains induces the polymer chains to pack more orderly and form large domains because of the additional H-bonding among urea groups. Accordingly, thin film mobilities of the conjugated D-A polymers with side chains entailing urea groups are largely boosted in comparison with those of polymers of the same backbones with either branching alkyl chains or branching/linear alkyl chains. (iv) The torsions of branching alkyl chains in conjugated D-A polymers can be inhibited to some extent upon incorporation of tiny amount of NMe 4 I in the thin film. As a result, the polymer thin films with NMe 4 I exhibit improved crystallinity, and charge mobilities can be boosted by more than 20 times. (v) Side chains with functional groups in the conjugated polymers can endow the thin film field-effect transistors (FETs) with sensing functionality. FETs with the conjugated polymer with -COOH groups in the side chains show sensitive, selective, and fast responses toward ammonia and amines, while FETs with the ultrathin films of the polymer containing tetra(ethylene glycol) (TEEG) in the side chains can sense alcohol vapors (in particular ethanol vapor) sensitively and selectively with fast response.

Conformational changes in fragments D and double-D from human fibrin(ogen) upon binding the peptide ligand Gly-His-Arg-Pro-amide.

PubMed

Everse, S J; Spraggon, G; Veerapandian, L; Doolittle, R F

1999-03-09

The structure of fragment double-D from human fibrin has been solved in the presence and absence of the peptide ligands that simulate the two knobs exposed by the removal of fibrinopeptides A and B, respectively. All told, six crystal structures have been determined, three of which are reported here for the first time: namely, fragments D and double-D with the peptide GHRPam alone and double-D in the absence of any peptide ligand. Comparison of the structures has revealed a series of conformational changes that are brought about by the various knob-hole interactions. Of greatest interest is a moveable "flap" of two negatively charged amino acids (Glubeta397 and Aspbeta398) whose side chains are pinned back to the coiled coil with a calcium atom bridge until GHRPam occupies the beta-chain pocket. Additionally, in the absence of the peptide ligand GPRPam, GHRPam binds to the gamma-chain pocket, a new calcium-binding site being formed concomitantly.

Small angle x-ray scattering study on the conformation of polystyrene in toluene during adding anti-solvent CO2

NASA Astrophysics Data System (ADS)

Liu, Yi; Chen, Dong-Feng; Wang, Hong-Li; Chen, Na; Li, Dan; Han, Bu-Xing; Rong, Li-Xia; Zhao, Hui; Wang, Jun; Dong, Bao-Zhong

2002-10-01

The conformation of polystyrene in the anti-solvent process of supercritical fluids (compressed CO2 + polystyrene + toluene) has been studied by small angle x-ray scattering with synchrotron radiation as an x-ray source. Coil-to-globule transformation of the polystyrene chain was observed with the increase of the anti-solvent CO2 pressure; i.e. polystyrene coiled at a pressure lower than the cloud point pressure (Pc) and turned into a globule with a uniform density at pressures higher than Pc. Fractal behaviour was also found in the chain contraction and the mass fractal dimension increased with increasing CO2 pressure.

Kinetics of Contact Formation and End-to-End Distance Distributions of Swollen Disordered Peptides

PubMed Central

Soranno, Andrea; Longhi, Renato; Bellini, Tommaso; Buscaglia, Marco

2009-01-01

Unstructured polypeptide chains are subject to various degrees of swelling or compaction depending on the combination of solvent condition and amino acid sequence. Highly denatured proteins generally behave like random-coils with excluded volume repulsion, whereas in aqueous buffer more compact conformations have been observed for the low-populated unfolded state of globular proteins as well as for naturally disordered sequences. To quantitatively account for the different mechanisms inducing the swelling of polypeptides, we have examined three 14-residues peptides in aqueous buffer and in denaturant solutions, including the well characterized AGQ repeat as a reference and two variants, in which we have successively introduced charged side chains and removed the glycines. Quenching of the triplet state of tryptophan by close contact with cysteine has been used in conjunction with Förster resonance energy transfer to study the equilibrium and kinetic properties of the peptide chains. The experiments enable accessing end-to-end root mean-square distance, probability of end-to-end contact formation and intrachain diffusion coefficient. The data can be coherently interpreted on the basis of a simple chain model with backbone angles obtained from a library of coil segments of proteins and hard sphere repulsion at each Cα position. In buffered water, we find that introducing charges in a glycine-rich sequence induces a mild chain swelling and a significant speed-up of the intrachain dynamics, whereas the removal of the glycines results in almost a two-fold increase of the chain volume and a drastic slowing down. In denaturants we observe a pronounced swelling of all the chains, with significant differences between the effect of urea and guanidinium chloride. PMID:19217868

Proteolytic processing of the pro beta chain of beta-hexosaminidase occurs at basic residues contained within an exposed disulfide loop structure.

PubMed

Sagherian, C; Poroszlay, S; Vavougios, G; Mahuran, D

1993-01-01

Lysosomal beta-hexosaminidase (EC 3.2.1.52) occurs as two major isozymes, Hex A (alpha beta) and Hex B (beta beta). The alpha and beta subunits are encoded by the HEXA and HEXB genes, respectively. Extensive homology in both the gene structures and deduced primary sequences demonstrate their common evolutionary origin. While undergoing similar proteolytic modifications in the lysosome, the pro beta polypeptide is additionally cleaved internally to produce the mature 24-30 kilodalton beta b and beta a chains. Previous data have suggested that this processing event occurs somewhere between residues Ser311 and Lys315. In this report we demonstrate that this area is located in a hydrophilic disulfide-loop structure (between Cys309 and Cys360). The cleavage event is prevented by the deletion through in vitro mutagenesis of the Arg312-Gln-Asn-Lys tetrapeptide or by its substitution with the aligned alpha residues (Gly-Ser-Glu-Pro). Reintroduction of either Arg312 or Lys315 reinstates the processing. Furthermore, we show that this area is not involved in lysosomal targeting of pro-Hex B, or in the increased stability or the variation in substrate specificity of the beta as compared with the alpha subunit. Our data suggest the presence of a novel lysosomal endoprotease. Like other endoproteases it is specific for basic amino acids; however, it cleaves on the amino-terminal side rather than the conventional carboxy-terminal side of such residues and then only if they are fully exposed to the lysosomal environment.(ABSTRACT TRUNCATED AT 250 WORDS)

Self-assembly of an amphiphilic macromolecule under spherical confinement: An efficient route to generate hollow nanospheres

NASA Astrophysics Data System (ADS)

Glagoleva, A. A.; Vasilevskaya, V. V.; Yoshikawa, K.; Khokhlov, A. R.

2013-12-01

In general, bio-macromolecules are composed of hydrophilic and hydrophobic moieties and are confined within small cavities, such as cell membranes and intracellular organelles. Here, we studied the self-organization of macromolecules having groups with different affinities to solvents under spherical nano-scale confinement by means of computer modeling. It is shown that depending on the interaction parameters of monomer units composed of side- and main-chain monomer groups along a single linear macromolecule and on cavity size, such amphiphilic polymers undergo the conformational transitions between hollow nanospheres, rod-like and folded cylindrical structures, and a necklace conformation with and without a particular ordering of beads. The diagram of the conformations in the variables the incompatibility parameter of monomer units and the cavity radius is constructed.

A protein-dependent side-chain rotamer library.

PubMed

Bhuyan, Md Shariful Islam; Gao, Xin

2011-12-14

Protein side-chain packing problem has remained one of the key open problems in bioinformatics. The three main components of protein side-chain prediction methods are a rotamer library, an energy function and a search algorithm. Rotamer libraries summarize the existing knowledge of the experimentally determined structures quantitatively. Depending on how much contextual information is encoded, there are backbone-independent rotamer libraries and backbone-dependent rotamer libraries. Backbone-independent libraries only encode sequential information, whereas backbone-dependent libraries encode both sequential and locally structural information. However, side-chain conformations are determined by spatially local information, rather than sequentially local information. Since in the side-chain prediction problem, the backbone structure is given, spatially local information should ideally be encoded into the rotamer libraries. In this paper, we propose a new type of backbone-dependent rotamer library, which encodes structural information of all the spatially neighboring residues. We call it protein-dependent rotamer libraries. Given any rotamer library and a protein backbone structure, we first model the protein structure as a Markov random field. Then the marginal distributions are estimated by the inference algorithms, without doing global optimization or search. The rotamers from the given library are then re-ranked and associated with the updated probabilities. Experimental results demonstrate that the proposed protein-dependent libraries significantly outperform the widely used backbone-dependent libraries in terms of the side-chain prediction accuracy and the rotamer ranking ability. Furthermore, without global optimization/search, the side-chain prediction power of the protein-dependent library is still comparable to the global-search-based side-chain prediction methods.

Side chain-side chain interactions of arginine with tyrosine and aspartic acid in Arg/Gly/Tyr-rich domains within plant glycine-rich RNA binding proteins.

PubMed

Kumaki, Yasuhiro; Nitta, Katsutoshi; Hikichi, Kunio; Matsumoto, Takeshi; Matsushima, Norio

2004-07-01

Plant glycine-rich RNA-binding proteins (GRRBPs) contain a glycine-rich region at the C-terminus whose structure is quite unknown. The C-terminal glycine-rich part is interposed with arginine and tyrosine (arginine/glycine/tyrosine (RGY)-rich domain). Comparative sequence analysis of forty-one GRRBPs revealed that the RGY-rich domain contains multiple repeats of Tyr-(Xaa)h-(Arg)k-(Xaa)l, where Xaa is mainly Gly, "k" is 1 or 2, and "h" and "l" range from 0 to 10. Two peptides, 1 (G1G2Y3G4G5G6R7R8D9G10) and 2 (G1G2R3R4D5G6G7Y8G9G10), corresponding to sections of the RGY-rich domain in Zea mays RAB15, were selected for CD and NMR experiments. The CD spectra indicate a unique, positive band near 228 nm in both peptides that has been ascribed to tyrosine residues in ordered structures. The pH titration by NMR revealed that a side chain-side chain interaction, presumably an H-Nepsilon...O=Cgamma hydrogen bonding interaction in the salt bridge, occurs between Arg (i) and Asp (i + 2). 1D GOESY experiments indicated the presence of NOE between the aromatic side chain proton and the arginine side chain proton in the two peptides suggesting strongly that the Arg (i) aromatic side chain interacts directly with the Tyr (i +/- 4 or i +/- 5) side chain.

Sparse networks of directly coupled, polymorphic, and functional side chains in allosteric proteins.

PubMed

Soltan Ghoraie, Laleh; Burkowski, Forbes; Zhu, Mu

2015-03-01

Recent studies have highlighted the role of coupled side-chain fluctuations alone in the allosteric behavior of proteins. Moreover, examination of X-ray crystallography data has recently revealed new information about the prevalence of alternate side-chain conformations (conformational polymorphism), and attempts have been made to uncover the hidden alternate conformations from X-ray data. Hence, new computational approaches are required that consider the polymorphic nature of the side chains, and incorporate the effects of this phenomenon in the study of information transmission and functional interactions of residues in a molecule. These studies can provide a more accurate understanding of the allosteric behavior. In this article, we first present a novel approach to generate an ensemble of conformations and an efficient computational method to extract direct couplings of side chains in allosteric proteins, and provide sparse network representations of the couplings. We take the side-chain conformational polymorphism into account, and show that by studying the intrinsic dynamics of an inactive structure, we are able to construct a network of functionally crucial residues. Second, we show that the proposed method is capable of providing a magnified view of the coupled and conformationally polymorphic residues. This model reveals couplings between the alternate conformations of a coupled residue pair. To the best of our knowledge, this is the first computational method for extracting networks of side chains' alternate conformations. Such networks help in providing a detailed image of side-chain dynamics in functionally important and conformationally polymorphic sites, such as binding and/or allosteric sites. © 2014 Wiley Periodicals, Inc.

Miscibility Evaluation Of The Next Generation Solvent With Polymers Currently Used At DWPF, MCU, And Saltstone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fondeur, F. F.

The Office of Waste Processing, within the Office of Technology Innovation and Development, funded the development of an enhanced Caustic-Side Solvent Extraction (CSSX) solvent for deployment at the Savannah River Site for removal of cesium from High Level Waste. This effort lead to the development of the Next Generation Solvent (NGS) with Tris (3,7-dimethyl octyl) guanidine (TiDG). The first deployment target for the NGS solvent is within the Modular CSSX Unit (MCU). Deployment of a new chemical within an existing facility requires verification that the new chemical components are compatible with the installed equipment. In the instance of a newmore » organic solvent, the primary focus is on compatibility of the solvent with organic polymers used in the affected facility. This report provides the calculated data from exposing these polymers to the Next Generation Solvent. An assessment of the dimensional stability of polymers known to be used or present in the MCU, Defense Waste Processing Facility (DWPF), and Saltstone facilities that will be exposed to the NGS showed that TiDG could selectively affect the elastomers and some thermoplastics to varying extents, but the typical use of these polymers in a confined geometry will likely prevent the NGS from impacting component performance. The polymers identified as of primary concern include Grafoil® (flexible graphite), Tefzel®, Isolast®, ethylene-propylene-diene monomer (EPDM) rubber, nitrile-butadiene rubber (NBR), styrene-butadiene rubber (SBR), ultra high molecular weight polyethylene (UHMWPE), and fluorocarbon rubber (FKM). Certain polymers like NBR and EPDM were found to interact mildly with NGS but their calculated swelling and the confined geometry will impede interaction with NGS. In addition, it was found that Vellumoid (cellulose fibers-reinforced glycerin and protein) may leach protein and Polyvinyl Chloride (PVC) may leach plasticizer (such as Bis-Ethylhexyl-Phthalates) into the NGS solvent. Either case will not impact decontamination or immobilization operations at Savannah River Site (SRS). Some applications have zero tolerance for dimensional changes such as the operation of valves while other applications a finite dimensional change improves the function of the application such as seals and gaskets. Additional considerations are required before using the conclusions from this work to judge outcomes in field applications. Decane, a component of Isopar L that is most likely to interact with the polymers, mildly interacted with the elastomers and the propylene based polymers but their degree of swelling is at most 10% and the confined geometry that they are typically placed in indicate this is not significant. In addition, it was found that Vellumoid may leach protein into the NGS solvent. Since Vellumoid is used at the mixer in Saltstone where it sees minimum quantities of solvent, this leaching has no effect on the extraction process at MCU or the immobilization process at saltstone. No significant interaction is expected between MaxCalix and the polymers and elastomers used at MCU, DWPF, and Saltstone. Overall, minimal and insignificant interactions are expected on extraction and immobilization operations when MCU switches from CSSX to NGS solvent. It is expected that contacting NGS will not accelerate the aging rate of polymers and elastomers under radiation and heat. This is due to the minimal interaction between NGS and the polymers and the confined geometries for these polymers. SRNL recommends the use of the HSP method (for screening) and some testing to evaluate the impact of other organic such as alcohols, glycolate, and their byproducts on the polymers used throughout the site.« less

Multifunctional Diketopyrrolopyrrole-Based Conjugated Polymers with Perylene Bisimide Side Chains.

PubMed

Li, Cheng; Yu, Changshi; Lai, Wenbin; Liang, Shijie; Jiang, Xudong; Feng, Guitao; Zhang, Jianqi; Xu, Yunhua; Li, Weiwei

2017-11-24

Two conjugated polymers based on diketopyrrolopyrrole (DPP) in the main chain with different content of perylene bisimide (PBI) side chains are developed. The influence of PBI side chain on the photovoltaic performance of these DPP-based conjugated polymers is systematically investigated. This study suggests that the PBI side chains can not only alter the absorption spectrum and energy level but also enhance the crystallinity of conjugated polymers. As a result, such polymers can act as electron donor, electron acceptor, and single-component active layer in organic solar cells. These findings provide a new guideline for the future molecular design of multifunctional conjugated polymers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Choline-amino acid ionic liquids: past and recent achievements about the structure and properties of these really "green" chemicals.

PubMed

Gontrani, Lorenzo

2018-06-01

The structure of choline-amino acid ionic liquids, atoxic task-specific solvents composed of materials originated from renewable feedstocks, is reviewed in this letter. The varied and strong interactions that these liquids are capable of establishing are largely dependent on their structure and confer them outstanding solvating properties with respect to a large number of different solutes. Among the experimental methods capable of yielding structural insight, the energy-dispersive version of X-Ray diffraction, that uses the Bremsstrahlung radiation of the X-Ray tube, is a technique very well suited to investigate these liquid systems. The diffraction spectra of five choline-amino acid ionic liquids, recently measured, are reported and discussed; in particular, the presence or absence of the medium-range order pre-peak is related to the presence of polar groups within the amino acid side chain that destroys the hydrophobic interactions between aliphatic chains. In the final section, a recent example of choline-amino acid ionic liquids as for ancient paper preservation and two other interesting results are discussed at the end.

Bottlebrush-Guided Polymer Crystallization Resulting in Supersoft and Reversibly Moldable Physical Networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daniel, William F. M.; Xie, Guojun; Vatankhah Varnoosfaderani, Mohammad

The goal of this study is to use ABA triblock copolymers with central bottlebrush B segments and crystalline linear chain A segments to demonstrate the effect of side chains on the formation and mechanical properties of physical networks cross-linked by crystallites. For this purpose, a series of bottlebrush copolymers was synthesized consisting of central amorphous bottlebrush polymer segments with a varying degree of polymerization (DP) of poly(n-butyl acrylate) (PnBA) side chains and linear tail blocks of crystallizable poly(octadecyl acrylate-stat-docosyl acrylate) (poly(ODA-stat-DA)). The materials were generated by sequential atom transfer radical polymerization (ATRP) steps starting with a series of bifunctional macroinitiatorsmore » followed by the growth of two ODA-stat-DA linear-chain tails and eventually growing poly(nBA) side chains with increasing DPs. Crystallization of the poly(ODA-stat-DA) tails resulted in a series of reversible physical networks with bottlebrush strands bridging crystalline cross-links. They displayed very low moduli of elasticity of the order of 10 3–10 4 Pa. These distinct properties are due to the bottlebrush architecture, wherein densely grafted side chains play a dual role by facilitating disentanglement of the network strands and confining crystallization of the linear-chain tails. This combination leads to physical cross-linking of supersoft networks without percolation of the crystalline phase. The cross-link density was effectively controlled by the DP of the side chains with respect to the DP of the linear tails (n A). Furthermore, shorter side chains allowed for crystallization of the linear tails of neighboring bottlebrushes, while steric repulsion between longer side chains hindered the phase separation and crystallization process and prevented network formation.« less

Bottlebrush-Guided Polymer Crystallization Resulting in Supersoft and Reversibly Moldable Physical Networks

DOE PAGES

Daniel, William F. M.; Xie, Guojun; Vatankhah Varnoosfaderani, Mohammad; ...

2017-02-24

The goal of this study is to use ABA triblock copolymers with central bottlebrush B segments and crystalline linear chain A segments to demonstrate the effect of side chains on the formation and mechanical properties of physical networks cross-linked by crystallites. For this purpose, a series of bottlebrush copolymers was synthesized consisting of central amorphous bottlebrush polymer segments with a varying degree of polymerization (DP) of poly(n-butyl acrylate) (PnBA) side chains and linear tail blocks of crystallizable poly(octadecyl acrylate-stat-docosyl acrylate) (poly(ODA-stat-DA)). The materials were generated by sequential atom transfer radical polymerization (ATRP) steps starting with a series of bifunctional macroinitiatorsmore » followed by the growth of two ODA-stat-DA linear-chain tails and eventually growing poly(nBA) side chains with increasing DPs. Crystallization of the poly(ODA-stat-DA) tails resulted in a series of reversible physical networks with bottlebrush strands bridging crystalline cross-links. They displayed very low moduli of elasticity of the order of 10 3–10 4 Pa. These distinct properties are due to the bottlebrush architecture, wherein densely grafted side chains play a dual role by facilitating disentanglement of the network strands and confining crystallization of the linear-chain tails. This combination leads to physical cross-linking of supersoft networks without percolation of the crystalline phase. The cross-link density was effectively controlled by the DP of the side chains with respect to the DP of the linear tails (n A). Furthermore, shorter side chains allowed for crystallization of the linear tails of neighboring bottlebrushes, while steric repulsion between longer side chains hindered the phase separation and crystallization process and prevented network formation.« less

Radiolytic Treatment of the Next-Generation Caustic-Side Solvent Extraction (NGS) Solvent and its Effect on the NGS Process

DOE PAGES

Roach, Benjamin D.; Williams, Neil J.; Duncan, Nathan C.; ...

2014-12-01

We show in this work that the solvent used in the Next Generation Caustic-Side Solvent Extraction (NGS) process can withstand a radiation dose well in excess of the dose it would receive in multiple years of treating legacy salt waste at the US Department of Energy Savannah River Site. The solvent was subjected to a maximum of 50 kGy of gamma radiation while in dynamic contact with each of the aqueous phases of the current NGS process, namely SRS-15 (a highly caustic waste simulant), sodium hydroxide scrub solution (0.025 M), and boric acid strip solution (0.01 M). Bench-top testing ofmore » irradiated solvent confirmed that irradiation has inconsequential impact on the extraction, scrubbing, and stripping performance of the solvent up to 13 times the estimated 0.73 kGy/y annual absorbed dose. Lastly, stripping performance is the most sensitive step to radiation, deteriorating more due to buildup of p-sec-butylphenol (SBP) and possibly other proton-ionizable products than to degradation of the guanidine suppressor, as shown by chemical analyses.« less

Radiolytic Treatment of the Next-Generation Caustic-Side Solvent Extraction (NGS) Solvent and its Effect on the NGS Process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roach, Benjamin D.; Williams, Neil J.; Duncan, Nathan C.

We show in this work that the solvent used in the Next Generation Caustic-Side Solvent Extraction (NGS) process can withstand a radiation dose well in excess of the dose it would receive in multiple years of treating legacy salt waste at the US Department of Energy Savannah River Site. The solvent was subjected to a maximum of 50 kGy of gamma radiation while in dynamic contact with each of the aqueous phases of the current NGS process, namely SRS-15 (a highly caustic waste simulant), sodium hydroxide scrub solution (0.025 M), and boric acid strip solution (0.01 M). Bench-top testing ofmore » irradiated solvent confirmed that irradiation has inconsequential impact on the extraction, scrubbing, and stripping performance of the solvent up to 13 times the estimated 0.73 kGy/y annual absorbed dose. Lastly, stripping performance is the most sensitive step to radiation, deteriorating more due to buildup of p-sec-butylphenol (SBP) and possibly other proton-ionizable products than to degradation of the guanidine suppressor, as shown by chemical analyses.« less

Relationship between ion pair geometries and electrostatic strengths in proteins.

PubMed Central

Kumar, Sandeep; Nussinov, Ruth

2002-01-01

The electrostatic free energy contribution of an ion pair in a protein depends on two factors, geometrical orientation of the side-chain charged groups with respect to each other and the structural context of the ion pair in the protein. Conformers in NMR ensembles enable studies of the relationship between geometry and electrostatic strengths of ion pairs, because the protein structural contexts are highly similar across different conformers. We have studied this relationship using a dataset of 22 unique ion pairs in 14 NMR conformer ensembles for 11 nonhomologous proteins. In different NMR conformers, the ion pairs are classified as salt bridges, nitrogen-oxygen (N-O) bridges and longer-range ion pairs on the basis of geometrical criteria. In salt bridges, centroids of the side-chain charged groups and at least a pair of side-chain nitrogen and oxygen atoms of the ion-pairing residues are within a 4 A distance. In N-O bridges, at least a pair of the side-chain nitrogen and oxygen atoms of the ion-pairing residues are within 4 A distance, but the distance between the side-chain charged group centroids is greater than 4 A. In the longer-range ion pairs, the side-chain charged group centroids as well as the side-chain nitrogen and oxygen atoms are more than 4 A apart. Continuum electrostatic calculations indicate that most of the ion pairs have stabilizing electrostatic contributions when their side-chain charged group centroids are within 5 A distance. Hence, most (approximately 92%) of the salt bridges and a majority (68%) of the N-O bridges are stabilizing. Most (approximately 89%) of the destabilizing ion pairs are the longer-range ion pairs. In the NMR conformer ensembles, the electrostatic interaction between side-chain charged groups of the ion-pairing residues is the strongest for salt bridges, considerably weaker for N-O bridges, and the weakest for longer-range ion pairs. These results suggest empirical rules for stabilizing electrostatic interactions in proteins. PMID:12202384

Structural symmetry breaking of silicon containing polymers and their relation with electrical conductivity and Raman active vibrations

NASA Astrophysics Data System (ADS)

Cabrera, Alejandro; González, Carmen; Tagle, Luis; Terraza, Claudio; Volkmann, Ulrich; Barriga, Andrés; Ramos, Esteban; Pavez, Maximiliano

2011-03-01

The incorporation of silicon into the polymeric main chain or side groups can provide an enhancement in chemical, physical and mechanical properties. We report an efficient method for the synthesis of polymers containing silicon in the main chain, from the polycondensation reactions of four optically active carboxylic diacid. The solubility of the polymers, the molecular weight, the glass transition and the thermal stability were studied by standard techniques. Raman spectroscopy was used to probe the conformation of stretching modes as function of the temperature. The conductivity measurements indicated that the alignment of the molecules is a crucial parameter for electrical performance. When the polymers were exposed to iodine, charge transfer increased their mobility and decreased their optical band gaps. These novel properties highlight the possibility to generate alternative active opto-electronics polymers.

Structure and Dynamics of Solvated Polymers near a Silica Surface: On the Different Roles Played by Solvent.

PubMed

Perrin, Elsa; Schoen, Martin; Coudert, François-Xavier; Boutin, Anne

2018-04-26

Whereas it is experimentally known that the inclusion of nanoparticles in hydrogels can lead to a mechanical reinforcement, a detailed molecular understanding of the adhesion mechanism is still lacking. Here we use coarse-grained molecular dynamics simulations to investigate the nature of the interface between silica surfaces and solvated polymers. We show how differences in the nature of the polymer and the polymer-solvent interactions can lead to drastically different behavior of the polymer-surface adhesion. Comparing explicit and implicit solvent models, we conclude that this effect cannot be fully described in an implicit solvent. We highlight the crucial role of polymer solvation for the adsorption of the polymer chain on the silica surface, the significant dynamics of polymer chains on the surface, and details of the modifications in the structure solvated polymer close to the interface.

Solvent-free, supersoft and superelastic bottlebrush melts and networks

NASA Astrophysics Data System (ADS)

Daniel, William F. M.; Burdyńska, Joanna; Vatankhah-Varnoosfaderani, Mohammad; Matyjaszewski, Krzysztof; Paturej, Jarosław; Rubinstein, Michael; Dobrynin, Andrey V.; Sheiko, Sergei S.

2016-02-01

Polymer gels are the only viable class of synthetic materials with a Young's modulus below 100 kPa conforming to biological applications, yet those gel properties require a solvent fraction. The presence of a solvent can lead to phase separation, evaporation and leakage on deformation, diminishing gel elasticity and eliciting inflammatory responses in any surrounding tissues. Here, we report solvent-free, supersoft and superelastic polymer melts and networks prepared from bottlebrush macromolecules. The brush-like architecture expands the diameter of the polymer chains, diluting their entanglements without markedly increasing stiffness. This adjustable interplay between chain diameter and stiffness makes it possible to tailor the network's elastic modulus and extensibility without the complications associated with a swollen gel. The bottlebrush melts and elastomers exhibit an unprecedented combination of low modulus (~100 Pa), high strain at break (~1,000%), and extraordinary elasticity, properties that are on par with those of designer gels.

Enhanced n-Doping Efficiency of a Naphthalenediimide-Based Copolymer through Polar Side Chains for Organic Thermoelectrics

PubMed Central

2018-01-01

N-doping of conjugated polymers either requires a high dopant fraction or yields a low electrical conductivity because of their poor compatibility with molecular dopants. We explore n-doping of the polar naphthalenediimide–bithiophene copolymer p(gNDI-gT2) that carries oligoethylene glycol-based side chains and show that the polymer displays superior miscibility with the benzimidazole–dimethylbenzenamine-based n-dopant N-DMBI. The good compatibility of p(gNDI-gT2) and N-DMBI results in a relatively high doping efficiency of 13% for n-dopants, which leads to a high electrical conductivity of more than 10–1 S cm–1 for a dopant concentration of only 10 mol % when measured in an inert atmosphere. We find that the doped polymer is able to maintain its electrical conductivity for about 20 min when exposed to air and recovers rapidly when returned to a nitrogen atmosphere. Overall, solution coprocessing of p(gNDI-gT2) and N-DMBI results in a larger thermoelectric power factor of up to 0.4 μW K–2 m–1 compared to other NDI-based polymers. PMID:29457139

Enhanced n-Doping Efficiency of a Naphthalenediimide-Based Copolymer through Polar Side Chains for Organic Thermoelectrics.

PubMed

Kiefer, David; Giovannitti, Alexander; Sun, Hengda; Biskup, Till; Hofmann, Anna; Koopmans, Marten; Cendra, Camila; Weber, Stefan; Anton Koster, L Jan; Olsson, Eva; Rivnay, Jonathan; Fabiano, Simone; McCulloch, Iain; Müller, Christian

2018-02-09

N-doping of conjugated polymers either requires a high dopant fraction or yields a low electrical conductivity because of their poor compatibility with molecular dopants. We explore n-doping of the polar naphthalenediimide-bithiophene copolymer p(gNDI-gT2) that carries oligoethylene glycol-based side chains and show that the polymer displays superior miscibility with the benzimidazole-dimethylbenzenamine-based n-dopant N-DMBI. The good compatibility of p(gNDI-gT2) and N-DMBI results in a relatively high doping efficiency of 13% for n-dopants, which leads to a high electrical conductivity of more than 10 -1 S cm -1 for a dopant concentration of only 10 mol % when measured in an inert atmosphere. We find that the doped polymer is able to maintain its electrical conductivity for about 20 min when exposed to air and recovers rapidly when returned to a nitrogen atmosphere. Overall, solution coprocessing of p(gNDI-gT2) and N-DMBI results in a larger thermoelectric power factor of up to 0.4 μW K -2 m -1 compared to other NDI-based polymers.

Ionizable side chains at catalytic active sites of enzymes.

PubMed

Jimenez-Morales, David; Liang, Jie; Eisenberg, Bob

2012-05-01

Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1,072 Å(3). The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes.

Ionizable Side Chains at Catalytic Active Sites of Enzymes

PubMed Central

Jimenez-Morales, David; Liang, Jie

2012-01-01

Catalytic active sites of enzymes of known structure can be well defined by a modern program of computational geometry. The CASTp program was used to define and measure the volume of the catalytic active sites of 573 enzymes in the Catalytic Site Atlas database. The active sites are identified as catalytic because the amino acids they contain are known to participate in the chemical reaction catalyzed by the enzyme. Acid and base side chains are reliable markers of catalytic active sites. The catalytic active sites have 4 acid and 5 base side chains, in an average volume of 1072 Å3. The number density of acid side chains is 8.3 M (in chemical units); the number density of basic side chains is 10.6 M. The catalytic active site of these enzymes is an unusual electrostatic and steric environment in which side chains and reactants are crowded together in a mixture more like an ionic liquid than an ideal infinitely dilute solution. The electrostatics and crowding of reactants and side chains seems likely to be important for catalytic function. In three types of analogous ion channels, simulation of crowded charges accounts for the main properties of selectivity measured in a wide range of solutions and concentrations. It seems wise to use mathematics designed to study interacting complex fluids when making models of the catalytic active sites of enzymes. PMID:22484856

Insecticide solvents: interference with insecticidal action.

PubMed

Brattsten, L B; Wilkinson, C F

1977-06-10

Several commercial solvent mixtures commonly used as insecticide carriers in spray formulations increase by more than threefold the microsomal N-demethylation of p-chloro N-methylaniline in midgut preparations of southern army-worm (Spodoptera eridania) larvae exposed orally to the test solvents. Under laboratory conditions, the same solvent mixtures exhibit a protective action against the in vivo toxicity of the insecticide carbaryl to the larvae. The data are discussed with respect to possible solvent-insecticide interactions occurring under field conditions and, more broadly, to potential toxicological hazards of these solvents to humans.

Unlocking Chain Exchange in Highly Amphiphilic Block Polymer Micellar Systems: Influence of Agitation.

PubMed

Murphy, Ryan P; Kelley, Elizabeth G; Rogers, Simon A; Sullivan, Millicent O; Epps, Thomas H

2014-11-18

Chain exchange between block polymer micelles in highly selective solvents, such as water, is well-known to be arrested under quiescent conditions, yet this work demonstrates that simple agitation methods can induce rapid chain exchange in these solvents. Aqueous solutions containing either pure poly(butadiene- b -ethylene oxide) or pure poly(butadiene- b -ethylene oxide- d 4 ) micelles were combined and then subjected to agitation by vortex mixing, concentric cylinder Couette flow, or nitrogen gas sparging. Subsequently, the extent of chain exchange between micelles was quantified using small angle neutron scattering. Rapid vortex mixing induced chain exchange within minutes, as evidenced by a monotonic decrease in scattered intensity, whereas Couette flow and sparging did not lead to measurable chain exchange over the examined time scale of hours. The linear kinetics with respect to agitation time suggested a surface-limited exchange process at the air-water interface. These findings demonstrate the strong influence of processing conditions on block polymer solution assemblies.

Differences in Ribosome Binding and Sarcin/Ricin Loop Depurination by Shiga and Ricin Holotoxins.

PubMed

Li, Xiao-Ping; Tumer, Nilgun E

2017-04-11

Both ricin and Shiga holotoxins display no ribosomal activity in their native forms and need to be activated to inhibit translation in a cell-free translation inhibition assay. This is because the ribosome binding site of the ricin A chain (RTA) is blocked by the B subunit in ricin holotoxin. However, it is not clear why Shiga toxin 1 (Stx1) or Shiga toxin 2 (Stx2) holotoxin is not active in a cell-free system. Here, we compare the ribosome binding and depurination activity of Stx1 and Stx2 holotoxins with the A1 subunits of Stx1 and Stx2 using either the ribosome or a 10-mer RNA mimic of the sarcin/ricin loop as substrates. Our results demonstrate that the active sites of Stx1 and Stx2 holotoxins are blocked by the A2 chain and the B subunit, while the ribosome binding sites are exposed to the solvent. Unlike ricin, which is enzymatically active, but cannot interact with the ribosome, Stx1 and Stx2 holotoxins are enzymatically inactive but can interact with the ribosome.

Molecular modeling of calmodulin: a comparison with crystallographic data

NASA Technical Reports Server (NTRS)

McDonald, J. J.; Rein, R.

1989-01-01

Two methods of side-chain placement on a modeled protein have been examined. Two molecular models of calmodulin were constructed that differ in the treatment of side chains prior to optimization of the molecule. A virtual bond analysis program developed by Purisima and Scheraga was used to determine the backbone conformation based on 2.2 angstroms resolution C alpha coordinates for the molecules. In the first model, side chains were initially constructed in an extended conformation. In the second model, a conformational grid search technique was employed. Calcium ions were treated explicitly during energy optimization using CHARMM. The models are compared to a recently published refined crystal structure of calmodulin. The results indicate that the initial choices for side-chains, but also significant effects on the main-chain conformation and supersecondary structure. The conformational differences are discussed. Analysis of these and other methods makes possible the formulation of a methodology for more appropriate side-chain placement in modeled proteins.

Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate- and guanidinium-containing residues in a β-hairpin.

PubMed

Kuo, Hsiou-Ting; Liu, Shing-Lung; Chiu, Wen-Chieh; Fang, Chun-Jen; Chang, Hsien-Chen; Wang, Wei-Ren; Yang, Po-An; Li, Jhe-Hao; Huang, Shing-Jong; Huang, Shou-Ling; Cheng, Richard P

2015-05-01

β-Sheet is one of the major protein secondary structures. Oppositely charged residues are frequently observed across neighboring strands in antiparallel sheets, suggesting the importance of cross-strand ion pairing interactions. The charged amino acids Asp, Glu, Arg, and Lys have different numbers of hydrophobic methylenes linking the charged functionality to the backbone. To investigate the effect of side chain length of guanidinium- and carboxylate-containing residues on lateral cross-strand ion pairing interactions at non-hydrogen-bonded positions, β-hairpin peptides containing Zbb-Agx (Zbb = Asp, Glu, Aad in increasing length; Agx = Agh, Arg, Agb, Agp in decreasing length) sequence patterns were studied by NMR methods. The fraction folded population and folding energy were derived from the chemical shift deviation data. Peptides with high fraction folded populations involved charged residue side chain lengths that supported high strand propensity. Double mutant cycle analysis was used to determine the interaction energy for the potential lateral ion pairs. Minimal interaction was observed between residues with short side chains, most likely due to the diffused positive charge on the guanidinium group, which weakened cross-strand electrostatic interactions with the carboxylate side chain. Only the Aad-Arg/Agh interactions with long side chains clearly exhibited stabilizing energetics, possibly relying on hydrophobics. A survey of a non-redundant protein structure database revealed that the statistical sheet pair propensity followed the trend Asp-Arg < Glu-Arg, implying the need for matching long side chains. This suggested the need for long side chains on both guanidinium-bearing and carboxylate-bearing residues to stabilize the β-hairpin motif.

Temperature-dependent micellar structures in poly(styrene-b-isoprene) diblock copolymer solutions near the critical micelle temperature

NASA Astrophysics Data System (ADS)

Bang, Joona; Viswanathan, Karthik; Lodge, Timothy P.; Park, Moon Jeong; Char, Kookheon

2004-12-01

The temperature dependence of the micelle structures formed by poly(styrene-b-isoprene) (SI) diblock copolymers in the selective solvents diethyl phthalate (DEP) and tetradecane (C14), which are selective for the PS and PI blocks, respectively, have been investigated by small angle neutron scattering (SANS). Two nearly symmetric SI diblock copolymers, one with a perdeuterated PS block and the other with a perdeuterated PI block, were examined in both DEP and C14. The SANS scattering length density of the solvent was matched closely to either the core or the corona block. The resulting core and corona contrast data were fitted with a detailed model developed by Pedersen and co-workers. The fits provide quantitative information on micellar characteristics such as aggregation number, core size, overall size, solvent fraction in the core, and corona thickness. As temperature increases, the solvent selectivity decreases, leading to substantial solvent swelling of the core and a decrease in the aggregation number and core size. Both core and corona chains are able to relax their conformations near the critical micelle temperature due to a decrease in the interfacial tension, even though the corona chains are always under good solvent conditions.

Differently ordered TiO2 nanoarrays regulated by solvent polarity, and their photocatalytic performances

NASA Astrophysics Data System (ADS)

Hu, Wenyuan; Dong, Faqin; Zhang, Jing; Liu, Mingxue; He, Huichao; Wu, Yadong; Yang, Dingming; Deng, Hongquan

2018-06-01

Special TiO2 arrays with exposed facets were prepared in different solvents by low- temperature solvothermal synthesis. The morphology, phase and photocatalytic performance influenced by the various solvent polarities were characterized using field emission scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Raman spectra and electrochemical testing. The results show that differences of solvent polarity are the main force driving differences in array growth; therefore, anatase TiO2 arrays with different crystal facets can be synthesized by tuning solvent polarity. TiO2 arrays prepared in cyclohexane are the best at oxidizing methyl orange through photocatalysis, followed by arrays prepared in toluene and ethanol. Arrays prepared in toluene are the best at reducing Cr(VI) photocatalytically, followed by those prepared in cyclohexane and ethanol. These differences in photocatalytic power are due to the ratio among the different crystal facets that are exposed, which affects the migration behavior of the photogenerated electrons and holes. In addition, the probable growth mechanisms of self-assembled ordered TiO2 arrays in different solvents are described.

Loop electrostatics modulates the intersubunit interactions in ferritin.

PubMed

Bernacchioni, Caterina; Ghini, Veronica; Pozzi, Cecilia; Di Pisa, Flavio; Theil, Elizabeth C; Turano, Paola

2014-11-21

Functional ferritins are 24-mer nanocages that self-assemble with extended contacts between pairs of 4-helix bundle subunits coupled in an antiparallel fashion along the C2 axes. The largest intersubunit interaction surface in the ferritin nanocage involves helices, but contacts also occur between groups of three residues midway in the long, solvent-exposed L-loops of facing subunits. The anchor points between intersubunit L-loop pairs are the salt bridges between the symmetry-related, conserved residues Asp80 and Lys82. The resulting quaternary structure of the cage is highly soluble and thermostable. Substitution of negatively charged Asp80 with a positively charged Lys in homopolymeric M ferritin introduces electrostatic repulsions that inhibit the oligomerization of the ferritin subunits. D80K ferritin was present in inclusion bodies under standard overexpressing conditions in E. coli, contrasting with the wild type protein. Small amounts of fully functional D80K nanocages formed when expression was slowed. The more positively charged surface results in a different solubility profile and D80K crystallized in a crystal form with a low density packing. The 3D structure of D80K variant is the same as wild type except for the side chain orientations of Lys80 and facing Lys82. When three contiguous Lys groups are introduced in D80KI81K ferritin variant the nanocage assembly is further inhibited leading to lower solubility and reduced thermal stability. Here, we demonstrate that the electrostatic pairing at the center of the L-loops has a specific kinetic role in the self-assembly of ferritin nanocages.

Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature-sensitive phenotype.

PubMed

Oji, Vinzenz; Hautier, Juliette Mazereeuw; Ahvazi, Bijan; Hausser, Ingrid; Aufenvenne, Karin; Walker, Tatjana; Seller, Natalia; Steijlen, Peter M; Küster, Wolfgang; Hovnanian, Alain; Hennies, Hans Christian; Traupe, Heiko

2006-11-01

Bathing suit ichthyosis (BSI) is a striking and unique clinical form of autosomal recessive congenital ichthyosis characterized by pronounced scaling on the bathing suit areas but sparing of the extremities and the central face. Here we report on a series of 10 BSI patients. Our genetic, ultrastructural and biochemical investigations show that BSI is caused by transglutaminase-1 (TGase-1) deficiency. Altogether, we identified 13 mutations in TGM1-among them seven novel missense mutations and one novel nonsense mutation. Structural modeling for the Tyr276Asn mutation reveals that the residue is buried in the hydrophobic interior of the enzyme and that the hydroxyl side chain of Tyr276 is exposed to solvent in a cavity of the enzyme. Cryosections of healthy skin areas demonstrated an almost normal TGase activity, in contrast to the affected BSI skin, which only showed a cytoplasmic and clearly reduced TGase-1 activity. The distribution of TGase-1 substrates in the epidermis of affected skin corresponded to the situation in TGase-1 deficiency. Interestingly, the expression of TGase-3 and cathepsin D was reduced. Digital thermography validated a striking correlation between warmer body areas and presence of scaling in patients suggesting a decisive influence of the skin temperature. In situ TGase testing in skin of BSI patients demonstrated a marked decrease of enzyme activity when the temperature was increased from 25 to 37 degrees C. We conclude that BSI is caused by TGase-1 deficiency and suggest that it is a temperature-sensitive phenotype.

Side chain engineering of poly-thiophene and its impact on crystalline silicon based hybrid solar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zellmeier, M.; Rappich, J.; Nickel, N. H.

The influence of ether groups in the side chain of spin coated regioregular polythiophene derivatives on the polymer layer formation and the hybrid solar cell properties was investigated using electrical, optical, and X-ray diffraction experiments. The polymer layers are of high crystallinity but the polymer with 3 ether groups in the side chain (P3TOT) did not show any vibrational fine structure in the UV-Vis spectrum. The presence of ether groups in the side chains leads to better adhesion resulting in thinner and more homogeneous polymer layers. This, in turn, enhances the electronic properties of the planar c-Si/poly-thiophene hybrid solar cell.more » We find that the power conversion efficiency increases with the number of ether groups in the side chains, and a maximum power conversion efficiency of η = 9.6% is achieved even in simple planar structures.« less

Force Field Development and Molecular Dynamics of [NiFe] Hydrogenase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Dayle MA; Xiong, Yijia; Straatsma, TP

2012-05-09

Classical molecular force-field parameters describing the structure and motion of metal clusters in [NiFe] hydrogenase enzymes can be used to compare the dynamics and thermodynamics of [NiFe] under different oxidation, protonation, and ligation circumstances. Using density functional theory (DFT) calculations of small model clusters representative of the active site and the proximal, medial, and distal Fe/S metal centers and their attached protein side chains, we have calculated classical force-field parameters for [NiFe] in reduced and oxidized states, including internal coordinates, force constants, and atom-centered charges. Derived force constants revealed that cysteinate ligands bound to the metal ions are more flexiblemore » in the Ni-B active site, which has a bridging hydroxide ligand, than in the Ni-C active site, which has a bridging hydride. Ten nanosecond all-atom, explicit-solvent MD simulations of [NiFe] hydrogenase in oxidized and reduced catalytic states established the stability of the derived force-field parameters in terms of C{alpha} and metal cluster fluctuations. Average active site structures from the protein MD simulations are consistent with [NiFe] structures from the Protein Data Bank, suggesting that the derived force-field parameters are transferrable to other hydrogenases beyond the structure used for testing. A comparison of experimental H{sub 2}-production rates demonstrated a relationship between cysteinate side chain rotation and activity, justifying the use of a fully dynamic model of [NiFe] metal cluster motion.« less

25. BUILDING NO. 527, DEHYDRATING HOUSE, DETAIL OF SOLVENT RECOVERY ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

25. BUILDING NO. 527, DEHYDRATING HOUSE, DETAIL OF SOLVENT RECOVERY DUCTS. SOUTH SIDE OF BUILDING. - Picatinny Arsenal, 500 Area, Powder Factory & Power House, State Route 15 near I-80, Dover, Morris County, NJ

Revealing Surface Waters on an Antifreeze Protein by Fusion Protein Crystallography Combined with Molecular Dynamic Simulations.

PubMed

Sun, Tianjun; Gauthier, Sherry Y; Campbell, Robert L; Davies, Peter L

2015-10-08

Antifreeze proteins (AFPs) adsorb to ice through an extensive, flat, relatively hydrophobic surface. It has been suggested that this ice-binding site (IBS) organizes surface waters into an ice-like clathrate arrangement that matches and fuses to the quasi-liquid layer on the ice surface. On cooling, these waters join the ice lattice and freeze the AFP to its ligand. Evidence for the generality of this binding mechanism is limited because AFPs tend to crystallize with their IBS as a preferred protein-protein contact surface, which displaces some bound waters. Type III AFP is a 7 kDa globular protein with an IBS made up two adjacent surfaces. In the crystal structure of the most active isoform (QAE1), the part of the IBS that docks to the primary prism plane of ice is partially exposed to solvent and has clathrate waters present that match this plane of ice. The adjacent IBS, which matches the pyramidal plane of ice, is involved in protein-protein crystal contacts with few surface waters. Here we have changed the protein-protein contacts in the ice-binding region by crystallizing a fusion of QAE1 to maltose-binding protein. In this 1.9 Å structure, the IBS that fits the pyramidal plane of ice is exposed to solvent. By combining crystallography data with MD simulations, the surface waters on both sides of the IBS were revealed and match well with the target ice planes. The waters on the pyramidal plane IBS were loosely constrained, which might explain why other isoforms of type III AFP that lack the prism plane IBS are less active than QAE1. The AFP fusion crystallization method can potentially be used to force the exposure to solvent of the IBS on other AFPs to reveal the locations of key surface waters.

Covalent modification of proteins by cocaine

NASA Astrophysics Data System (ADS)

Deng, Shi-Xian; Bharat, Narine; Fischman, Marian C.; Landry, Donald W.

2002-03-01

Cocaine covalently modifies proteins through a reaction in which the methyl ester of cocaine acylates the -amino group of lysine residues. This reaction is highly specific in vitro, because no other amino acid reacts with cocaine, and only cocaine's methyl ester reacts with the lysine side chain. Covalently modified proteins were present in the plasma of rats and human subjects chronically exposed to cocaine. Modified endogenous proteins are immunogenic, and specific antibodies were elicited in mouse and detected in the plasma of human subjects. Covalent modification of proteins could explain cocaine's autoimmune effects and provide a new biochemical approach to cocaine's long-term actions.

Calcium Coordination Solids for pH-Triggered Release of Olsalazine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levine, Dana J.; Gonzalez, Miguel I.; Legendre, Christina M.

Here, calcium coordination solids were synthesized and evaluated for delivery of olsalazine (H 4olz), an anti-inflammatory compound used for treatment of ulcerative colitis. The materials include one-dimensional Ca(H 2olz)•4H 2O chains, two-dimensional Ca(H 2olz)•2H 2O sheets, and a three-dimensional metal-organic framework Ca(H 2olz)•2DMF (DMF= N,N-dimethylformamide). The framework undergoes structural changes in response to solvent, forming a dense Ca(H 2olz) phase when exposed to aqueous HCl. The compounds Ca(H 2olz)•xH 2O (x=0, 2, 4) were each pressed into pellets and exposed to simulated gastrointestinal fluids to mimic the passage of a pill from the acidic stomach to the pH-neutral intestines. Allmore » three calcium materials exhibited a delayed release of olsalazine relative to Na 2(H 2olz), the commercial formulation, illustrating how formulation of a drug within an extended coordination solid can serve to tune its solubility and performance.« less

Calcium Coordination Solids for pH-Triggered Release of Olsalazine

DOE PAGES

Levine, Dana J.; Gonzalez, Miguel I.; Legendre, Christina M.; ...

2017-09-12

Here, calcium coordination solids were synthesized and evaluated for delivery of olsalazine (H 4olz), an anti-inflammatory compound used for treatment of ulcerative colitis. The materials include one-dimensional Ca(H 2olz)•4H 2O chains, two-dimensional Ca(H 2olz)•2H 2O sheets, and a three-dimensional metal-organic framework Ca(H 2olz)•2DMF (DMF= N,N-dimethylformamide). The framework undergoes structural changes in response to solvent, forming a dense Ca(H 2olz) phase when exposed to aqueous HCl. The compounds Ca(H 2olz)•xH 2O (x=0, 2, 4) were each pressed into pellets and exposed to simulated gastrointestinal fluids to mimic the passage of a pill from the acidic stomach to the pH-neutral intestines. Allmore » three calcium materials exhibited a delayed release of olsalazine relative to Na 2(H 2olz), the commercial formulation, illustrating how formulation of a drug within an extended coordination solid can serve to tune its solubility and performance.« less

A combinatorial approach to protein docking with flexible side chains.

PubMed

Althaus, Ernst; Kohlbacher, Oliver; Lenhof, Hans-Peter; Müller, Peter

2002-01-01

Rigid-body docking approaches are not sufficient to predict the structure of a protein complex from the unbound (native) structures of the two proteins. Accounting for side chain flexibility is an important step towards fully flexible protein docking. This work describes an approach that allows conformational flexibility for the side chains while keeping the protein backbone rigid. Starting from candidates created by a rigid-docking algorithm, we demangle the side chains of the docking site, thus creating reasonable approximations of the true complex structure. These structures are ranked with respect to the binding free energy. We present two new techniques for side chain demangling. Both approaches are based on a discrete representation of the side chain conformational space by the use of a rotamer library. This leads to a combinatorial optimization problem. For the solution of this problem, we propose a fast heuristic approach and an exact, albeit slower, method that uses branch-and-cut techniques. As a test set, we use the unbound structures of three proteases and the corresponding protein inhibitors. For each of the examples, the highest-ranking conformation produced was a good approximation of the true complex structure.

Conformational Changes of the Alanine Dipeptide in Water-Ethanol Binary Mixtures.

PubMed

Almeida, Glauco G; Cordeiro, João M M; Martín, M Elena; Aguilar, Manuel A

2016-04-12

Experimental work developed in the last years has evidenced the capacity of alcohols and polyalcohols to modify the energy landscape of peptides and proteins. However, the mechanism underlying this effect is not clear. Taking as a model system the alanine dipeptide (AD) we perform a QM/MM study in water, ethanol, and a 40-60% in volume water-ethanol mixture. The AD molecule was described at the MP2/aug-cc-pVDZ level. In polar solution, only αR and PPII conformers contribute in an appreciable way to the conformational equilibrium. The final in solution αR-PPII free energy difference is determined from the interplay between the internal energy of the dipeptide and the solute-solvent interaction free energy. Internal energy favors the formation of PPII, whereas, on the contrary, solute-solvent interaction is favorable to αR, so any factor that decreases the solute-solvent interaction free energy will increase the PPII population. The addition of ethanol increases the stability of the PPII conformer. Our results point to the presence of preferential solvation in this system, the composition of the first solvation shell in the binary mixture being dominated by water molecules. Remarkably, this fact does not affect the differential conformational stability that is controlled by long-range interactions. From the analysis of solvent density maps it is concluded that, in the water-ethanol mixture, ethanol molecules are more likely found around the alanine side chain and the carbonyl group, but while in PPII ethanol molecules interact mainly with the carbonyl group of the N-terminal end, in C5 the interaction is with the carbonyl group of the C-terminal end. In αR, ethanol interacts with both carbonyl groups.

Atoms-in-molecules study of the genetically encoded amino acids. III. Bond and atomic properties and their correlations with experiment including mutation-induced changes in protein stability and genetic coding.

PubMed

Matta, Chérif F; Bader, Richard F W

2003-08-15

This article presents a study of the molecular charge distributions of the genetically encoded amino acids (AA), one that builds on the previous determination of their equilibrium geometries and the demonstrated transferability of their common geometrical parameters. The properties of the charge distributions are characterized and given quantitative expression in terms of the bond and atomic properties determined within the quantum theory of atoms-in-molecules (QTAIM) that defines atoms and bonds in terms of the observable charge density. The properties so defined are demonstrated to be remarkably transferable, a reflection of the underlying transferability of the charge distributions of the main chain and other groups common to the AA. The use of the atomic properties in obtaining an understanding of the biological functions of the AA, whether free or bound in a polypeptide, is demonstrated by the excellent statistical correlations they yield with experimental physicochemical properties. A property of the AA side chains of particular importance is the charge separation index (CSI), a quantity previously defined as the sum of the magnitudes of the atomic charges and which measures the degree of separation of positive and negative charges in the side chain of interest. The CSI values provide a correlation with the measured free energies of transfer of capped side chain analogues, from the vapor phase to aqueous solution, yielding a linear regression equation with r2 = 0.94. The atomic volume is defined by the van der Waals isodensity surface and it, together with the CSI, which accounts for the electrostriction of the solvent, yield a linear regression (r2 = 0.98) with the measured partial molar volumes of the AAs. The changes in free energies of transfer from octanol to water upon interchanging 153 pairs of AAs and from cyclohexane to water upon interchanging 190 pairs of AAs, were modeled using only three calculated parameters (representing electrostatic and volume contributions) yielding linear regressions with r2 values of 0.78 and 0.89, respectively. These results are a prelude to the single-site mutation-induced changes in the stabilities of two typical proteins: ubiquitin and staphylococcal nuclease. Strong quadratic correlations (r2 approximately 0.9) were obtained between DeltaCSI upon mutation and each of the two terms DeltaDeltaH and TDeltaDeltaS taken from recent and accurate differential scanning calorimetry experiments on ubiquitin. When the two terms are summed to yield DeltaDeltaG, the quadratic terms nearly cancel, and the result is a simple linear fit between DeltaDeltaG and DeltaCSI with r2 = 0.88. As another example, the change in the stability of staphylococcal nuclease upon mutation has been fitted linearly (r2 = 0.83) to the sum of a DeltaCSI term and a term representing the change in the van der Waals volume of the side chains upon mutation. The suggested correlation of the polarity of the side chain with the second letter of the AA triplet genetic codon is given concrete expression in a classification of the side chains in terms of their CSI values and their group dipole moments. For example, all amino acids with a pyrimidine base as their second letter in mRNA possess side-chain CSI < or = 2.8 (with the exception of Cys), whereas all those with CSI > 2.8 possess an purine base. The article concludes with two proposals for measuring and predicting molecular complementarity: van der Waals complementarity expressed in terms of the van der Waals isodensity surface and Lewis complementarity expressed in terms of the local charge concentrations and depletions defined by the topology of the Laplacian of the electron density. A display of the experimentally accessible Laplacian distribution for a folded protein would offer a clear picture of the operation of the "stereochemical code" proposed as the determinant in the folding process. Copyright 2003 Wiley-Liss, Inc.

Studies on the solvation dynamics of coumarin 153 in 1-ethyl-3-methylimidazolium alkylsulfate ionic liquids: dependence on alkyl chain length.

PubMed

Das, Sudhir Kumar; Sarkar, Moloy

2012-08-06

Steady-state and time-resolved fluorescence behavior of coumarin 153 (C153) is investigated in a series of 1-ethyl-3-methylimidazolium alkylsulfate ([C(2)mim][C(n)OSO(3)]) ionic liquids differing only in the length of the linear alkyl chain (n = 4, 6, and 8) in the anion. The aim of the present study is to understand the role of alkyl chain length in solute rotation and solvation dynamics of C153 in these ionic liquids. The blueshift observed in the steady-state absorption and emission maxima of C153 on going from the C(4)OSO(3) to the C(8)OSO(3) system indicates increasing nonpolar character of the microenvironment of the solute with increasing length of the alkyl side chain of the anion of the ionic liquids. The average solvation time is also found to increase on changing the substituent from butyl to octyl, and this is attributed to the increase in the bulk viscosity of the ILs. A steady blueshift of the time-zero maximum of the fluorescence spectrum with increasing alkyl chain length also indicates that the probe molecule experiences a less polar environment in the early part of the dynamics. Rotational dynamics of C153 are also analyzed by using the Stokes-Einstein-Debye (SED), Gierer-Wirtz (GW), and Dote-Kivelson-Schwartz (DKS) theories. Analyses of the results seem to suggest decoupling of the rotational motion of the probe from solvent viscosity. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improved packing of protein side chains with parallel ant colonies.

PubMed

Quan, Lijun; Lü, Qiang; Li, Haiou; Xia, Xiaoyan; Wu, Hongjie

2014-01-01

The accurate packing of protein side chains is important for many computational biology problems, such as ab initio protein structure prediction, homology modelling, and protein design and ligand docking applications. Many of existing solutions are modelled as a computational optimisation problem. As well as the design of search algorithms, most solutions suffer from an inaccurate energy function for judging whether a prediction is good or bad. Even if the search has found the lowest energy, there is no certainty of obtaining the protein structures with correct side chains. We present a side-chain modelling method, pacoPacker, which uses a parallel ant colony optimisation strategy based on sharing a single pheromone matrix. This parallel approach combines different sources of energy functions and generates protein side-chain conformations with the lowest energies jointly determined by the various energy functions. We further optimised the selected rotamers to construct subrotamer by rotamer minimisation, which reasonably improved the discreteness of the rotamer library. We focused on improving the accuracy of side-chain conformation prediction. For a testing set of 442 proteins, 87.19% of X1 and 77.11% of X12 angles were predicted correctly within 40° of the X-ray positions. We compared the accuracy of pacoPacker with state-of-the-art methods, such as CIS-RR and SCWRL4. We analysed the results from different perspectives, in terms of protein chain and individual residues. In this comprehensive benchmark testing, 51.5% of proteins within a length of 400 amino acids predicted by pacoPacker were superior to the results of CIS-RR and SCWRL4 simultaneously. Finally, we also showed the advantage of using the subrotamers strategy. All results confirmed that our parallel approach is competitive to state-of-the-art solutions for packing side chains. This parallel approach combines various sources of searching intelligence and energy functions to pack protein side chains. It provides a frame-work for combining different inaccuracy/usefulness objective functions by designing parallel heuristic search algorithms.

22. VIEW LOOKING FORWARD INTO CHAIN LOCKER FROM PORT SIDE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

22. VIEW LOOKING FORWARD INTO CHAIN LOCKER FROM PORT SIDE ENTRY THROUGH CHAIN LOCKER BULKHEAD. PAWL BITT SHOWN IN FOREGROUND - Pilot Schooner "Alabama", Moored in harbor at Vineyard Haven, Vineyard Haven, Dukes County, MA

Impact of organic solvents and environmental pollutants on the physiological function in petrol filling workers.

PubMed

Uzma, Nazia; Salar, B M Khaja Mohinuddin; Kumar, B Santhosh; Aziz, Nusrat; David, M Anthony; Reddy, V Devender

2008-09-01

Long term exposure to solvents and air pollutants can lead to deleterious effects on respiratory, haematological and thyroid functioning. The aim of this study was to investigate whether chronic exposure to solvents like benzene and pollutants like carbon monoxide in petrol filling workers had adverse effect on blood parameters, thyroid and respiratory functions. The study group consisted of 42 healthy, non-smoker petrol filling workers, aged 20-50 years with work (exposure) duration from 2-15 years while 36 healthy subjects of the same age group served as controls. Physical examination and measurement of pulmonary functions by portable electronic spirometer were performed. Complete blood pictures (CBP) were determined by normal haematology lab procedure and hormones by Chemiluminescence immunoassay (CLIA) light absorption techniques. There was a significant decrease in the lung volumes and capacities; the restrictive pattern was more prevalent in the workers when compared with the control groups. But in the workers exposed for long period (more than 10 years) the restrictive pattern was changed to mixed pattern. A significant increase in haemoglobin (Hb) (>16 mg %) and red blood cells (RBC) (5.4 million cells/mm3) were observed in workers with longer period of exposure when compared with the control subjects (14.483 mg% and 4.83 million cells/mm3 for Hb and RBC respectively). White blood cell count except eosinophils and platelets were significantly lower in workers compared to controls. Marked increase in the tetra iodothyroinine (T4), free thyroxine (T4F) level and significant decrease in thyroid stimulating hormones (TSH), and tri-iodothyronine (T3) were observed between long term exposed and non-exposed groups. Till now researchers focused only on the effect of solvents in workers professionally exposed to solvents without considering the effect of concomittant air pollution. The result obtained from present study indicates that there is a significant toxic effect of solvents and air pollutants on workers exposed for longer duration. Improved detection and prevention technologies are needed to answer environmentally related health questions for petrol filling workers.

Liquid crystal polymers: evidence of hairpin defects in nematic main chains, comparison with side chain polymers

NASA Astrophysics Data System (ADS)

Li, M. H.; Brûlet, A.; Keller, P.; Cotton, J. P.

1996-09-01

This article describes the conformation of two species of liquid crystalline polymers as revealed by small angle neutron scattering. The results obtained with side chain polymers are recalled. The procedure used to analyze the scattering data of main chains in the nematic phase is reported in this paper. It permits a demonstration of the existence of hairpins. Comparison of both polymer species shows that in the isotropic phase, the two polymers adopt a random coil conformation. In the nematic phase, the conformations are very different; the side chains behave as a melt of penetrable random coils whereas the main chains behave as a nematic phase of non penetrable cylinders.

Water isotope effect on the thermostability of a polio viral RNA hairpin: A metadynamics study.

PubMed

Pathak, Arup K; Bandyopadhyay, Tusar

2017-04-28

Oral polio vaccine is considered to be the most thermolabile of all the common childhood vaccines. Despite heavy water (D 2 O) having been known for a long time to stabilise attenuated viral RNA against thermodegradation, the molecular underpinnings of its mechanism of action are still lacking. Whereas, understanding the basis of D 2 O action is an important step that might reform the way other thermolabile drugs are stored and could possibly minimize the cold chain problem. Here using a combination of parallel tempering and well-tempered metadynamics simulation in light water (H 2 O) and in D 2 O, we have fully described the free energy surface associated with the folding/unfolding of a RNA hairpin containing a non-canonical basepair motif, which is conserved within the 3'-untranslated region of poliovirus-like enteroviruses. Simulations reveal that in heavy water (D 2 O) there is a considerable increase of the stability of the folded basin as monitored through an intramolecular hydrogen bond (HB), size, shape, and flexibility of RNA structures. This translates into a higher melting temperature in D 2 O by 41 K when compared with light water (H 2 O). We have explored the hydration dynamics of the RNA, hydration shell around the RNA surface, and spatial dependence of RNA-solvent collective HB dynamics in the two water systems. Simulation in heavy water clearly showed that D 2 O strengthens the HB network in the solvent, lengthens inter-residue water-bridge lifetime, and weakens dynamical coupling of the hairpin to its solvation environment, which enhances the rigidity of solvent exposed sites of the native configurations. The results might suggest that like other added osmoprotectants, D 2 O can act as a thermostabilizer when used as a solvent.

Water isotope effect on the thermostability of a polio viral RNA hairpin: A metadynamics study

NASA Astrophysics Data System (ADS)

Pathak, Arup K.; Bandyopadhyay, Tusar

2017-04-01

Oral polio vaccine is considered to be the most thermolabile of all the common childhood vaccines. Despite heavy water (D2O) having been known for a long time to stabilise attenuated viral RNA against thermodegradation, the molecular underpinnings of its mechanism of action are still lacking. Whereas, understanding the basis of D2O action is an important step that might reform the way other thermolabile drugs are stored and could possibly minimize the cold chain problem. Here using a combination of parallel tempering and well-tempered metadynamics simulation in light water (H2O) and in D2O, we have fully described the free energy surface associated with the folding/unfolding of a RNA hairpin containing a non-canonical basepair motif, which is conserved within the 3'-untranslated region of poliovirus-like enteroviruses. Simulations reveal that in heavy water (D2O) there is a considerable increase of the stability of the folded basin as monitored through an intramolecular hydrogen bond (HB), size, shape, and flexibility of RNA structures. This translates into a higher melting temperature in D2O by 41 K when compared with light water (H2O). We have explored the hydration dynamics of the RNA, hydration shell around the RNA surface, and spatial dependence of RNA-solvent collective HB dynamics in the two water systems. Simulation in heavy water clearly showed that D2O strengthens the HB network in the solvent, lengthens inter-residue water-bridge lifetime, and weakens dynamical coupling of the hairpin to its solvation environment, which enhances the rigidity of solvent exposed sites of the native configurations. The results might suggest that like other added osmoprotectants, D2O can act as a thermostabilizer when used as a solvent.

Disulfide bonding arrangements in active forms of the somatomedin B domain of human vitronectin.

PubMed

Kamikubo, Yuichi; De Guzman, Roberto; Kroon, Gerard; Curriden, Scott; Neels, Jaap G; Churchill, Michael J; Dawson, Philip; Ołdziej, Stanisław; Jagielska, Anna; Scheraga, Harold A; Loskutoff, David J; Dyson, H Jane

2004-06-01

The N-terminal cysteine-rich somatomedin B (SMB) domain (residues 1-44) of the human glycoprotein vitronectin contains the high-affinity binding sites for plasminogen activator inhibitor-1 (PAI-1) and the urokinase receptor (uPAR). We previously showed that the eight cysteine residues of recombinant SMB (rSMB) are organized into four disulfide bonds in a linear uncrossed pattern (Cys(5)-Cys(9), Cys(19)-Cys(21), Cys(25)-Cys(31), and Cys(32)-Cys(39)). In the present study, we use an alternative method to show that this disulfide bond arrangement remains a major preferred one in solution, and we determine the solution structure of the domain using NMR analysis. The solution structure shows that the four disulfide bonds are tightly packed in the center of the domain, replacing the traditional hydrophobic core expected for a globular protein. The few noncysteine hydrophobic side chains form a cluster on the outside of the domain, providing a distinctive binding surface for the physiological partners PAI-1 and uPAR. The hydrophobic surface consists mainly of side chains from the loop formed by the Cys(25)-Cys(31) disulfide bond, and is surrounded by conserved acidic and basic side chains, which are likely to contribute to the specificity of the intermolecular interactions of this domain. Interestingly, the overall fold of the molecule is compatible with several arrangements of the disulfide bonds. A number of different disulfide bond arrangements were able to satisfy the NMR restraints, and an extensive series of conformational energy calculations performed in explicit solvent confirmed that several disulfide bond arrangements have comparable stabilization energies. An experimental demonstration of the presence of alternative disulfide conformations in active rSMB is provided by the behavior of a mutant in which Asn(14) is replaced by Met. This mutant has the same PAI-1 binding activity as rVN1-51, but its fragmentation pattern following cyanogen bromide treatment is incompatible with the linear uncrossed disulfide arrangement. These results suggest that active forms of the SMB domain may have a number of allowed disulfide bond arrangements as long as the Cys(25)-Cys(31) disulfide bond is preserved.

Synthesis and characterization of ionomers as polymer electrolytes for energy conversion devices

NASA Astrophysics Data System (ADS)

Oh, Hyukkeun

Single-ion conducting electrolytes present a unique alternative to traditional binary salt conductors used in lithium-ion batteries. Secondary lithium batteries are considered as one of the leading candidates to replace the combustible engines in automotive technology, however several roadblocks are present which prevent their widespread commercialization. Power density, energy density and safety properties must be improved in order to enable the current secondary lithium battery technology to compete with existing energy technologies. It has been shown theoretically that single-ion electrolytes can eliminate the salt concentration gradient and polarization loss in the cell that develops in a binary salt system, resulting in substantial improvements in materials utilization for high power and energy densities. While attempts to utilize single-ion conducting electrolytes in lithium-ion battery systems have been made, the low ionic conductivities prevented the successful operation of the battery cells in ambient conditions. This work focuses on designing single-ion conducting electrolytes with high ionic conductivities and electrochemical and mechanical stability which enables the stable charge-discharge performance of battery cells. Perfluorosulfonate ionomers are known to possess exceptionally high ionic conductivities due to the electron-withdrawing effect caused by the C-F bonds which stabilizes the negative charge of the anion, leading to a large number of free mobile cations. The effect of perfluorinated sulfonic acid side chains on transport properties of proton exchange membrane polymers was examinated via a comparison of three ionomers, having different side chain structures and a similar polymer backbone. The three different side chain structures were aryl-, pefluoro alkyl-, and alkyl-sulfonic acid groups, respectively. All ionomers were synthesized and characterized by 1H and 19F NMR. A novel ionomer synthesized with a pendant perfluorinated sulfonic acid group and a poly(ether ether ketone) backbone showed the highest proton conductivity and proton diffusion coefficient among the three ionomers, demonstrating the effect of the perfluorinated side chains. The proton conductivity of the novel ionomer was comparable to that of Nafion over a wide humidity range and temperature. A lithium perfluorosulfonate ionomer based on aromatic poly(arylene ether)s with pendant lithium perfluoroethyl sulfonates was prepared by ion exchange of the perlfuorosulfonic acid ionomer, and subsequently incoroporated into a lithium-ion battery cell as a single-ion conducting electrolyte. The microporous polymer film saturated with organic carbonates exhibited a nearly unity Li + transfer number, high ionic conductivity (e.g. > 10-3 S m-1 at room temperature) over a wide range of temperatures, high electrochemical stability, and excellent mechanical properties. Excellent cyclability with almost identical charge and discharge capacities have been demonstrated at ambient temperature in the batteries assembled from the prepared single-ion conductors. The mechanical stability of the polymer film was attributed to the rigid polymer backbone which was largely unaffected by the presence of plasticizing organic solvents, while the porous channels with high concentration of the perfluorinated side chains resulted in high ionic conductivity. The expected high charge-rate performance was not achieved, however, due to the high interfacial impedance present between the polymer electrolyte and the electrodes. Several procedural modifications were employed in order to decrease the interfacial impedance of the battery cell. The poly(arylene ether) based ionomer was saturated with an ionic liquid mixture, in order to explore the possibility of its application as a safe, inflammable electrolyte. A low-viscosity ionic liquid with high ionic conductivity, 1-butyl-3-methylimidazolium thiocyanate which has never been successfully utilized as an electrolyte for lithium-ion batteries was incorporated into a battery cell as a solvent mixture with propylene carbonate and lithium bis(trifluoromethane)sulfonimide impregnated in a free-standing hybrid electrolyte film. Outstanding ionic conductivity was achieved and the lithium half cell comprising a LTO cathode and a lithium metal anode separated by the solid polymer electrolyte showed good cyclability at room temperature and even at 0°C. The presence of a sufficient amount of propylene carbonate, which resulted in flammability of the polymer electrolyte, was discovered to be critical in the electrochemical stability of the polymer electrolyte.

Vacuum-integrated electrospray deposition for highly reliable polymer thin film.

PubMed

Park, Soohyung; Lee, Younjoo; Yi, Yeonjin

2012-10-01

Vacuum electrospray deposition (ESD) equipment was designed to prepare polymer thin films. The polymer solution can be injected directly into vacuum system through multi-stage pumping line, so that the solvent residues and ambient contaminants are highly reduced. To test the performance of ESD system, we fabricated organic photovoltaic cells (OPVCs) by injecting polymer solution directly onto the substrate inside a high vacuum chamber. The OPVC fabricated has the structure of Al∕P3HT:PCBM∕PEDOT:PSS∕ITO and was optimized by varying the speed of solution injection and concentration of the solution. The power conversion efficiency (PCE) of the optimized OPVC is 3.14% under AM 1.5G irradiation without any buffer layer at the cathode side. To test the advantages of the vacuum ESD, we exposed the device to atmosphere between the deposition steps of the active layer and cathode. This showed that the PCE of the vacuum processed device is 24% higher than that of the air exposed device and confirms the advantages of the vacuum prepared polymer film for high performance devices.

Determining rotational dynamics of the guanidino group of arginine side chains in proteins by carbon-detected NMR.

PubMed

Gerecht, Karola; Figueiredo, Angelo Miguel; Hansen, D Flemming

2017-09-16

Arginine residues are imperative for many active sites and protein-interaction interfaces. A new NMR-based method is presented to determine the rotational dynamics around the N ε -C ζ bond of arginine side chains. An application to a 19 kDa protein shows that the strengths of interactions involving arginine side chains can be characterised.

Cellulose Crystal Dissolution in Imidazolium-Based Ionic Liquids: A Theoretical Study.

PubMed

Uto, Takuya; Yamamoto, Kazuya; Kadokawa, Jun-Ichi

2018-01-11

The highly crystalline nature of cellulose results in poor processability and solubility, necessitating the search for solvents that can efficiently dissolve this material. Thus, ionic liquids (ILs) have recently been shown to be well suited for this purpose, although the corresponding dissolution mechanism has not been studied in detail. Herein, we adopt a molecular dynamics (MD) approach to study the dissolution of model cellulose crystal structures in imidazolium-based ILs and gain deep mechanistic insights, demonstrating that dissolution involves IL penetration-induced cleavage of hydrogen bonds between cellulose molecular chains. Moreover, we reveal that in ILs with high cellulose dissolving power (powerful solvents, such as 1-allyl-3-methylimidazolium chloride and 1-ethyl-3-methylimidazolium chloride), the above molecular chains are peeled from the crystal phase and subsequently dispersed in the solvent, whereas no significant structural changes are observed in poor-dissolving-power solvents. Finally, we utilize MD trajectory analysis to show that the solubility of microcrystalline cellulose is well correlated with the number of intermolecular hydrogen bonds in cellulose crystals. The obtained results allow us to conclude that both anions and cations of high-dissolving-power ILs contribute to the stepwise breakage of hydrogen bonds between cellulose chains, whereas this breakage does not occur to a sufficient extent in poorly solubilizing ILs.

Laser amplifier chain

DOEpatents

Hackel, Richard P.

1992-01-01

A laser amplifier chain has a plurality of laser amplifiers arranged in a chain to sequentially amplify a low-power signal beam to produce a significantly higher-power output beam. Overall efficiency of such a chain is improved if high-gain, low efficiency amplifiers are placed on the upstream side of the chain where only a very small fraction of the total pumped power is received by the chain and low-gain, high-efficiency amplifiers are placed on the downstream side where a majority of pumping energy is received by the chain.

Linear rheology and structure of molecular bottlebrushes with short side chains

DOE Office of Scientific and Technical Information (OSTI.GOV)

López-Barrón, Carlos R., E-mail: carlos.r.lopez-barron@exxonmobil.com; Brant, Patrick; Crowther, Donna J.

We investigate the microstructure and linear viscoelasticity of model molecular bottlebrushes (BBs) using rheological and small-angle X-ray and neutron scattering measurements. Our polymers have short atactic polypropylene (aPP) side chains of molecular weight ranging from 119 g/mol to 259 g/mol and narrow molecular weight distribution (M{sub w}/M{sub n} 1.02–1.05). The side chain molecular weights are a small fraction of the entanglement molecular weight of the corresponding linear polymer (M{sub e,aPP}= 7.05 kg/mol), and as such, they are unentangled. The morphology of the aPP BBs is characterized as semiflexible thick chains with small side chain interdigitation. Their dynamic master curves, obtained by time-temperature superposition,more » reveal two sequential relaxation processes corresponding to the segmental relaxation and the relaxation of the BB backbone. Due to the short length of the side chains, their fast relaxation could not be distinguished from the glassy relaxation. The fractional free volume is an increasing function of the side chain length (N{sub SC}). Therefore, the glassy behavior of these polymers as well as their molecular friction and dynamic properties are influenced by their N{sub SC} values. The apparent flow activation energies are a decreasing function of N{sub SC}, and their values explain the differences in zero-shear viscosity measured at different temperatures.« less

Characterization of amyloidogenesis of hen egg lysozyme in concentrated ethanol solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holley, Mikel; Eginton, Chris; Schaefer, David

We show that hen egg white lysozyme [HEWL] reproducibly forms amyloid fibrils in 80% ethanol at 22 deg. C with constant agitation. Fibril formation occurs over a time course of approximately 30 days, displays polymerization nucleation kinetics, and demonstrates a marked decrease in {alpha}-helical structure. Seeding with as little as 0.05% v/v of fibrils cleaved into smaller seed fragments by sonication abolishes the lag phase. Thioflavin T assays confirm the amyloid nature of the fibrils. Atomic force microscopy reveals unbranched amyloid fibrils with lengths varying between 1 and 3 {mu}m and heights ranging from 6-12 nm. The formation of amyloidmore » fibrils in predominantly organic solvents demonstrates that the basic principles guiding fibril formation arise from interactions of the peptide backbone rather than from interactions between the amino acid side chains.« less

Formation of non-spherical polymersomes driven by hydrophobic directional aromatic perylene interactions.

PubMed

Wong, Chin Ken; Mason, Alexander F; Stenzel, Martina H; Thordarson, Pall

2017-11-01

Polymersomes, made up of amphiphilic block copolymers, are emerging as a powerful tool in drug delivery and synthetic biology due to their high stability, chemical versatility, and surface modifiability. The full potential of polymersomes, however, has been hindered by a lack of versatile methods for shape control. Here we show that a range of non-spherical polymersome morphologies with anisotropic membranes can be obtained by exploiting hydrophobic directional aromatic interactions between perylene polymer units within the membrane structure. By controlling the extent of solvation/desolvation of the aromatic side chains through changes in solvent quality, we demonstrate facile access to polymersomes that are either ellipsoidal or tubular-shaped. Our results indicate that perylene aromatic interactions have a great potential in the design of non-spherical polymersomes and other structurally complex self-assembled polymer structures.

Co-solvents with high coulombic efficiency in propylene carbonate based electrolytes

DOEpatents

Liu, Gao; Zhao, Hui; Park, Sang-Jae

2017-06-27

A homologous series of cyclic carbonate or propylene carbonate (PC) analogue solvents with increasing length of linear alkyl substitutes were synthesized and used as co-solvents with PC for graphite based lithium ion half cells. A graphite anode reaches a capacity around 310 mAh/g in PC and its analogue co-solvents with 99.95% Coulombic efficiency. Cyclic carbonate co-solvents with longer alkyl chains are able to prevent exfoliation of graphite when used as co-solvents with PC. The cyclic carbonate co-solvents of PC compete for solvation of Li ion with PC solvent, delaying PC co-intercalation. Reduction products of PC on graphite surfaces via single-electron path form a stable Solid Electrolyte Interphase (SEI), which allows the reversible cycling of graphite.

Use of side-chain incompatibility for tailoring long-range p/n heterojunctions: photoconductive nanofibers formed by self-assembly of an amphiphilic donor-acceptor dyad consisting of oligothiophene and perylenediimide.

PubMed

Li, Wei-Shi; Saeki, Akinori; Yamamoto, Yohei; Fukushima, Takanori; Seki, Shu; Ishii, Noriyuki; Kato, Kenichi; Takata, Masaki; Aida, Takuzo

2010-07-05

To tailor organic p/n heterojunctions with molecular-level precision, a rational design strategy using side-chain incompatibility of a covalently connected donor-acceptor (D-A) dyad has been successfully carried out. An oligothiophene-perylenediimide dyad, when modified with triethylene glycol side chains at one terminus and dodecyl side chains at the other (2(Amphi)), self-assembles into nanofibers with a long-range D/A heterojunction. In contrast, when the dyad is modified with dodecyl side chains at both termini (2(Lipo)), ill-defined microfibers result. In steady-state measurements using microgap electrodes, a cast film of the nanofiber of 2(Amphi) displays far better photoconducting properties than that of the microfiber of 2(Lipo). Flash-photolysis time-resolved microwave conductivity measurements, in conjunction with transient absorption spectroscopy, clearly indicate that the nanofiber of 2(Amphi) intrinsically allows for better carrier generation and transport properties than the microfibrous assembly of 2(Lipo).

Partial molar volumes of proteins: amino acid side-chain contributions derived from the partial molar volumes of some tripeptides over the temperature range 10-90 degrees C.

PubMed

Häckel, M; Hinz, H J; Hedwig, G R

1999-11-15

The partial molar volumes of tripeptides of sequence glycyl-X-glycine, where X is one of the amino acids alanine, leucine, threonine, glutamine, phenylalanine, histidine, cysteine, proline, glutamic acid, and arginine, have been determined in aqueous solution over the temperature range 10-90 degrees C using differential scanning densitometry . These data, together with those reported previously, have been used to derive the partial molar volumes of the side-chains of all 20 amino acids. The side-chain volumes are critically compared with literature values derived using partial molar volumes for alternative model compounds. The new amino acid side-chain volumes, along with that for the backbone glycyl group, were used to calculate the partial specific volumes of several proteins in aqueous solution. The results obtained are compared with those observed experimentally. The new side-chain volumes have also been used to re-determine residue volume changes upon protein folding.

Chromatography of Penicillins, Penicilloates, and Penicilloylamides on Dextran Gels

PubMed Central

Hyslop, Newton E.; Milligan, Richard J.

1974-01-01

The factors influencing the chromatographic behavior on dextran gels of penicillins and their derivatives were investigated by comparing elution profiles and partition coefficients (KD and KAV) of penicillins differing in side-chain structure and among penicillin derivatives of identical side-chain but different nuclear structure. Under the conditions of pH and ionic strength employed (pH 7.4, 0.145 M NaCl, 0.05 M PO4), side-chain adsorptive effects best explained the anomalous behavior of benzylpenicillin and of oxacillin and its chlorine-substituted analogues. Polar side-chain substituents, such as the amino group of ampicillin and the carboxyl group of carbenicillin, and cleavage of the β-lactam ring, exemplified by penicilloates and penicilloylamines, both appeared to interfere with side-chain-directed adsorption. The differential adsorption of penicillins and their derivatives to dextran gels is not only of theoretical interest relative to the mechanism of chromatography but of practical application to analytical and preparative procedures in penicillin chemistry. PMID:15825415

Organic solvent exposure and hearing loss in a cohort of aluminium workers.

PubMed

Rabinowitz, P M; Galusha, D; Slade, M D; Dixon-Ernst, C; O'Neill, A; Fiellin, M; Cullen, M R

2008-04-01

Organic solvent exposure has been shown to cause hearing loss in animals and humans. Less is known about the risk of hearing loss due to solvent exposures typically found in US industry. The authors performed a retrospective cohort study to examine the relationship between solvent exposure and hearing loss in US aluminium industry workers. A cohort of 1319 workers aged 35 years or less at inception was followed for 5 years. Linkage of employment, industrial hygiene and audiometric surveillance records allowed for estimation of noise and solvent exposures and hearing loss rates over the study period. Study subjects were classified as "solvent exposed" or not, on the basis of industrial hygiene records linked with individual job histories. High frequency hearing loss was modelled as both a continuous and a dichotomous outcome. Typical solvent exposures involved mixtures of xylene, toluene and/or methyl ethyl ketone (MEK). Recorded solvent exposure levels varied widely both within and between jobs. In a multivariate logistic model, risk factors for high frequency hearing loss included age (OR = 1.06, p = 0.004), hunting or shooting (OR = 1.35, p = 0.049), noisy hobbies (OR = 1.74, p = 0.01), baseline hearing level (OR = 1.04, p<0.001) and solvent exposure (OR = 1.87, p = 0.004). A multivariate linear regression analysis similarly found significant associations between high frequency hearing loss and age (p<0.001), hunting or shooting (p<0.001), noisy hobbies (p = 0.03), solvent exposure (p<0.001) and baseline hearing (p = 0.03). These results suggest that occupational exposure to organic solvent mixtures is a risk factor for high frequency hearing loss, although the data do not allow conclusions about dose-response relationships. Industries with solvent-exposed workers should include such workers in hearing conservation programs.

Evaluation of cleaners for photovoltaic modules exposed in an outdoor environment

NASA Technical Reports Server (NTRS)

Knapp, W. D.

1979-01-01

Power recovery of silicone encapsulated and glass covered photovoltaic modules, exposed for two years to a suburban environment, was measured after washing with a variety of cleaners including detergents, abrasive soap, and hydrocarbon solvents. Silicone encapsulated modules in operating environments may experience significant power losses or require extensive periodic cleaning. Glass front-faced modules in similar situations are much less affected. Organic hydrocarbon solvents or abrasives were found to be about five times more effective than mild detergents in cleaning encapsulated modules.

Sum frequency generation and solid-state NMR study of the structure, orientation, and dynamics of polystyrene-adsorbed peptides

PubMed Central

Weidner, Tobias; Breen, Nicholas F.; Li, Kun; Drobny, Gary P.; Castner, David G.

2010-01-01

The power of combining sum frequency generation (SFG) vibrational spectroscopy and solid-state nuclear magnetic resonance (ssNMR) spectroscopy to quantify, with site specificity and atomic resolution, the orientation and dynamics of side chains in synthetic model peptides adsorbed onto polystyrene (PS) surfaces is demonstrated in this study. Although isotopic labeling has long been used in ssNMR studies to site-specifically probe the structure and dynamics of biomolecules, the potential of SFG to probe side chain orientation in isotopically labeled surface-adsorbed peptides and proteins remains largely unexplored. The 14 amino acid leucine-lysine peptide studied in this work is known to form an α-helical secondary structure at liquid-solid interfaces. Selective, individual deuteration of the isopropyl group in each leucine residue was used to probe the orientation and dynamics of each individual leucine side chain of LKα14 adsorbed onto PS. The selective isotopic labeling methods allowed SFG analysis to determine the orientations of individual side chains in adsorbed peptides. Side chain dynamics were obtained by fitting the deuterium ssNMR line shape to specific motional models. Through the combined use of SFG and ssNMR, the dynamic trends observed for individual side chains by ssNMR have been correlated with side chain orientation relative to the PS surface as determined by SFG. This combination provides a more complete and quantitative picture of the structure, orientation, and dynamics of these surface-adsorbed peptides than could be obtained if either technique were used separately. PMID:20628016

Highly conformationally constrained halogenated 6-spiroepoxypenicillins as probes for the bioactive side-chain conformation of benzylpenicillin

NASA Astrophysics Data System (ADS)

Shute, Richard E.; Jackson, David E.; Bycroft, Barrie W.

1989-06-01

The halogenated 6-spiroepoxypenicillins are a series of novel semisynthetic β-lactam compounds with highly conformationally restricted side chains incorporating an epoxide. Their biological activity profiles depend crucially on the configuration at position C-3 of that epoxide. In derivatives with aromatic-containing side chains, e.g., anilide, the 3 R-compounds possess notable Gram-positive antibacterial activity and potent β-lactamase inhibitory properties. The comparable 3S-compounds are antibacterially inactive, but retain β-lactamase inhibitory activity. Using the molecular simulation programs COSMIC and ASTRAL, we attempted to map a putative, lipophilic accessory binding site on the PBPs that must interact with the side-chain aromatic residue. Comparative computer-assisted modelling of the 3 R, and 3 S-anilides, along with benzylpenicillin, indicated that the available conformational space at room temperature for the side chains of the 3 R and the 3 S-anilides was mutually exclusive. The conformational space for the more flexible benzylpenicillin could accommodate the side chains of both the constrained penicillin derivatives. By a combination of van der Waals surface calculations and a pharmacophoric distance approach, closely coincident conformers of the 3 R-anilide and benzylpenicillin were identified. These conformers must be related to the antibacterial, `bioactive' conformer for the classical β-lactam antibiotics. From these proposed bioactive conformations, a model for the binding of benzylpenicillin to the PBPs relating the three-dimensional arrangement of a putative lipophilic S2-subsite, specific for the side-chain aromatic moiety, and the 3 α-carboxylate functionality is presented.

Next Generation Solvent Performance in the Modular Caustic Side Solvent Extraction Process - 15495

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Tara E.; Scherman, Carl; Martin, David

Changes to the Modular Caustic Side Solvent Extraction Unit (MCU) flow-sheet were implemented in the facility. Implementation included changing the scrub and strip chemicals and concentrations, modifying the O/A ratios for the strip, scrub, and extraction contactor banks, and blending the current BoBCalixC6 extractant-based solvent in MCU with clean MaxCalix extractant-based solvent. During the successful demonstration period, the MCU process was subject to rigorous oversight to ensure hydraulic stability and chemical/radionuclide analysis of the key process tanks (caustic wash tank, solvent hold tank, strip effluent hold tank, and decontaminated salt solution hold tank) to evaluate solvent carryover to downstream facilitiesmore » and the effectiveness of cesium removal from the liquid salt waste. Results indicated the extraction of cesium was significantly more effective with an average Decontamination Factor (DF) of 1,129 (range was 107 to 1,824) and that stripping was effective. The contactor hydraulic performance was stable and satisfactory, as indicated by contactor vibration, contactor rotational speed, and flow stability; all of which remained at or near target values. Furthermore, the Solvent Hold Tank (SHT) level and specific gravity was as expected, indicating that solvent integrity and organic hydraulic stability were maintained. The coalescer performances were in the range of processing results under the BOBCalixC6 flow sheet, indicating negligible adverse impact of NGS deployment. After the Demonstration period, MCU began processing via routine operations. Results to date reiterate the enhanced cesium extraction and stripping capability of the Next Generation Solvent (NGS) flow sheet. This paper presents process performance results of the NGS Demonstration and continued operations of MCU utilizing the blended BobCalixC6-MaxCalix solvent under the NGS flowsheet.« less

Enhanced bulk heterojunction devices prepared by thermal and solvent vapor annealing processes

DOEpatents

Forrest, Stephen R.; Thompson, Mark E.; Wei, Guodan; Wang, Siyi

2017-09-19

A method of preparing a bulk heterojunction organic photovoltaic cell through combinations of thermal and solvent vapor annealing are described. Bulk heterojunction films may prepared by known methods such as spin coating, and then exposed to one or more vaporized solvents and thermally annealed in an effort to enhance the crystalline nature of the photoactive materials.

Role of Side Chains in β-Sheet Self-Assembly into Peptide Fibrils. IR and VCD Spectroscopic Studies of Glutamic Acid-Containing Peptides.

PubMed

Tobias, Fernando; Keiderling, Timothy A

2016-05-10

Poly(glutamic acid) at low pH self-assembles after incubation at higher temperature into fibrils composed of antiparallel sheets that are stacked in a β2-type structure whose amide carbonyls have bifurcated H-bonds involving the side chains from the next sheet. Oligomers of Glu can also form such structures, and isotope labeling has provided insight into their out-of-register antiparallel structure [ Biomacromolecules 2013 , 14 , 3880 - 3891 ]. In this paper we report IR and VCD spectra and transmission electron micrograph (TEM) images for a series of alternately sequenced oligomers, Lys-(Aaa-Glu)5-Lys-NH2, where Aaa was varied over a variety of polar, aliphatic, or aromatic residues. Their spectral and TEM data show that these oligopeptides self-assemble into different structures, both local and morphological, that are dependent on both the nature of the Aaa side chains and growth conditions employed. Such alternate peptides substituted with small or polar residues, Ala and Thr, do not yield fibrils; but with β-branched aliphatic residues, Val and Ile, that could potentially pack with Glu side chains, these oligopeptides do show evidence of β2-stacking. By contrast, for Leu, with longer side chains, only β1-stacking is seen while with even larger Phe side chains, either β-form can be detected separately, depending on preparation conditions. These structures are dependent on high temperature incubation after reducing the pH and in some cases after sonication of initial fibril forms and reincubation. Some of these fibrillar peptides, but not all, show enhanced VCD, which can offer evidence for formation of long, multistrand, often twisted structures. Substitution of Glu with residues having selected side chains yields a variety of morphologies, leading to both β1- and β2-structures, that overall suggests two different packing modes for the hydrophobic side chains depending on size and type.

Role of Rhodobacter sphaeroides photosynthetic reaction center residue M214 in the composition, absorbance properties, and conformations of H(A) and B(A) cofactors.

PubMed

Saer, Rafael G; Hardjasa, Amelia; Rosell, Federico I; Mauk, A Grant; Murphy, Michael E P; Beatty, J Thomas

2013-04-02

In the native reaction center (RC) of Rhodobacter sphaeroides, the side chain of (M)L214 projects orthogonally toward the plane and into the center of the A branch bacteriopheophytin (BPhe) macrocycle. The possibility that this side chain is responsible for the dechelation of the central Mg(2+) of bacteriochlorophyll (BChl) was investigated by replacement of (M)214 with residues possessing small, nonpolar side chains that can neither coordinate nor block access to the central metal ion. The (M)L214 side chain was also replaced with Cys, Gln, and Asn to evaluate further the requirements for assembly of the RC with BChl in the HA pocket. Photoheterotrophic growth studies showed no difference in growth rates of the (M)214 nonpolar mutants at a low light intensity, but the growth of the amide-containing mutants was impaired. The absorbance spectra of purified RCs indicated that although absorbance changes are associated with the nonpolar mutations, the nonpolar mutant RC pigment compositions are the same as in the wild-type protein. Crystal structures of the (M)L214G, (M)L214A, and (M)L214N mutants were determined (determined to 2.2-2.85 Å resolution), confirming the presence of BPhe in the HA pocket and revealing alternative conformations of the phytyl tail of the accessory BChl in the BA site of these nonpolar mutants. Our results demonstrate that (i) BChl is converted to BPhe in a manner independent of the aliphatic side chain length of nonpolar residues replacing (M)214, (ii) BChl replaces BPhe if residue (M)214 has an amide-bearing side chain, (iii) (M)214 side chains containing sulfur are not sufficient to bind BChl in the HA pocket, and (iv) the (M)214 side chain influences the conformation of the phytyl tail of the BA BChl.

Organic solvent exposure and contrast sensitivity: comparing men and women

PubMed Central

Oliveira, A.R.; Campos, A.A.; de Andrade, M.J.O.; de Medeiros, P.C.B.; dos Santos, N.A.

2018-01-01

The goal of this study was to compare the visual contrast sensitivity (CS) of men and women exposed and not exposed to organic solvents. Forty-six volunteers of both genders aged between 18 and 41 years (mean±SD=27.72±6.28) participated. Gas station attendants were exposed to gas containing 46.30 ppm of solvents at a temperature of 304±274.39 K, humidity of 62.25±7.59% and ventilation of 0.69±0.46 m/s (a passive gas chromatography-based sampling method was used considering the microclimate variables). Visual CS was measured via the psychophysical method of two-alternative forced choice using vertical sinusoidal gratings with spatial frequencies of 0.2, 0.5, 1.0, 2.0, 5.0, 10.0, and 16.0 cpd (cycles per degree) and an average luminance of 34.4 cd/m2. The results showed that visual CS was significantly lower (P<0.05) in the following groups: i) exposed men compared to unexposed men at frequencies of 0.2, 0.5, 1.0, and 2.0 cpd; ii) exposed women compared to unexposed women at a frequency of 5.0 cpd; and iii) exposed women compared to exposed men at a frequency of 0.5 cpd, even at exposures below the tolerance limit (300 ppm). These results suggest that the visual CS of exposed men was impaired over a wider range of spatial frequencies than that of exposed women. This difference may have been due to the higher body fat content of women compared to that of men, suggesting that body fat in women can serve as a protective factor against neurotoxic effects. PMID:29340521

Simulation of a cellulose fiber in ionic liquid suggests a synergistic approach to dissolution

DOE PAGES

Mostofian, Barmak; Smith, Jeremy C.; Cheng, Xiaolin

2013-08-11

Ionic liquids dissolve cellulose in a more efficient and environmentally acceptable way than conventional methods in aqueous solution. An understanding of how ionic liquids act on cellulose is essential for improving pretreatment conditions and thus detailed knowledge of the interactions between the cations, anions and cellulose is necessary. Here in this study, to explore ionic liquid effects, we perform all-atom molecular dynamics simulations of a cellulose microfibril in 1-butyl-3-methylimidazolium chloride and analyze site–site interactions and cation orientations at the solute–solvent interface. The results indicate that Cl - anions predominantly interact with cellulose surface hydroxyl groups but with differences between chainsmore » of neighboring cellulose layers, referred to as center and origin chains; Cl- binds to C3-hydroxyls on the origin chains but to C2- and C6-hydroxyls on the center chains, thus resulting in a distinct pattern along glucan chains of the hydrophilic fiber surfaces. In particular, Cl - binding disrupts intrachain O3H–O5 hydrogen bonds on the origin chains but not those on the center chains. In contrast, Bmim + cations stack preferentially on the hydrophobic cellulose surface, governed by non-polar interactions with cellulose. Complementary to the polar interactions between Cl - and cellulose, the stacking interaction between solvent cation rings and cellulose pyranose rings can compensate the interaction between stacked cellulose layers, thus stabilizing detached cellulose chains. Moreover, a frequently occurring intercalation of Bmim + on the hydrophilic surface is observed, which by separating cellulose layers can also potentially facilitate the initiation of fiber disintegration. The results provide a molecular description why ionic liquids are ideal cellulose solvents, the concerted action of anions and cations on the hydrophobic and hydrophilic surfaces being key to the efficient dissolution of the amphiphilic carbohydrate.« less

Molecular dynamics simulation study of solvent effects on conformation and dynamics of polyethylene oxide and polypropylene oxide chains in water and in common organic solvents.

PubMed

Hezaveh, Samira; Samanta, Susruta; Milano, Giuseppe; Roccatano, Danilo

2012-03-28

In this paper, the conformation and dynamics properties of polyethylene oxide (PEO) and polypropylene oxide (PPO) polymer chains at 298 K have been studied in the melt and at infinite dilution condition in water, methanol, chloroform, carbon tetrachloride, and n-heptane using molecular dynamics simulations. The calculated density of PEO melt with chain lengths of n = 2, 3, 4, 5 and, for PPO, n = 7 are in good agreement with the available experimental data. The conformational properties of PEO and PPO show an increasing gauche preference for the O-C-C-O dihedral in the following order water>methanol>chloroform>carbon tetrachloride = n-heptane. On the contrary, the preference for trans conformation has a maximum in carbon tetrachloride and n-heptane followed in the order by chloroform, methanol, and water. The PEO conformational preferences are in qualitative agreement with results of NMR studies. PEO chains formed different types of hydrogen bonds with polar solvent molecules. In particular, the occurrence of bifurcated hydrogen bonding in chloroform was also observed. Radii of gyration of PEO chains of length larger than n = 9 monomers showed a good agreement with light scattering data in water and in methanol. For the shorter chains the observed deviations are probably due to the enhanced hydrophobic effects caused by the terminal methyl groups. For PEO the fitting of end-to-end distance distributions with the semi-flexible chain model at 298 K provided persistence lengths of 0.375 and 0.387 nm in water and methanol, respectively. Finally, the radius of gyration of Pluronic P85 turned out to be 2.25 ± 0.4 nm at 293 K in water in agreement with experimental data.

Molecular dynamics simulation study of solvent effects on conformation and dynamics of polyethylene oxide and polypropylene oxide chains in water and in common organic solvents

NASA Astrophysics Data System (ADS)

Hezaveh, Samira; Samanta, Susruta; Milano, Giuseppe; Roccatano, Danilo

2012-03-01

In this paper, the conformation and dynamics properties of polyethylene oxide (PEO) and polypropylene oxide (PPO) polymer chains at 298 K have been studied in the melt and at infinite dilution condition in water, methanol, chloroform, carbon tetrachloride, and n-heptane using molecular dynamics simulations. The calculated density of PEO melt with chain lengths of n = 2, 3, 4, 5 and, for PPO, n = 7 are in good agreement with the available experimental data. The conformational properties of PEO and PPO show an increasing gauche preference for the O-C-C-O dihedral in the following order water>methanol>chloroform>carbon tetrachloride = n-heptane. On the contrary, the preference for trans conformation has a maximum in carbon tetrachloride and n-heptane followed in the order by chloroform, methanol, and water. The PEO conformational preferences are in qualitative agreement with results of NMR studies. PEO chains formed different types of hydrogen bonds with polar solvent molecules. In particular, the occurrence of bifurcated hydrogen bonding in chloroform was also observed. Radii of gyration of PEO chains of length larger than n = 9 monomers showed a good agreement with light scattering data in water and in methanol. For the shorter chains the observed deviations are probably due to the enhanced hydrophobic effects caused by the terminal methyl groups. For PEO the fitting of end-to-end distance distributions with the semi-flexible chain model at 298 K provided persistence lengths of 0.375 and 0.387 nm in water and methanol, respectively. Finally, the radius of gyration of Pluronic P85 turned out to be 2.25 ± 0.4 nm at 293 K in water in agreement with experimental data.

Service life of counter-current chromatography coils.

PubMed

Conway, Walter D

2007-06-01

A multilayer coil of PTFE tubing, which failed after being used each workday for about 3 years in a type J centrifuge, was examined. Two types of defects were found. One, called crazes, occurs throughout the coil and does not leak initially, but may eventually lead to a short, axially oriented slit. Another, called indentations, is seen primarily in the innermost and other nearby layers. They are elongated, about 5 mm, indentations, usually on the central side of the tubing. These eventually crack and leak. PTFE tubing is permeable to air and hexane and expands by more than 1% when immersed in hexane, heptane or chloroform for a few days. It is suggested that the crazes result from exposure of the somewhat flexible tubing to the undulating centripetal force field in the coil-planet centrifuge, especially when further softened by solvent absorption. The indentations may result from carriage of the excess tubing length, created by solvent absorption, from the coil periphery to the coil center by the centripetal force field, which continuously travels from the peripheral tail to the central head of the coil. A 1% increase in coil length creates 74 cm of excess tubing in the 160-ml coils examined in this study. It is suggested that fluorinated ethylene propylene (FEP) tubing, especially when etched on the outside, may provide more stable CCC coils, since its expansion when exposed to organic solvents is 0.1 or less than that of PTFE.

Effect of solvent additives and P3HT on PDTSTTz/PCBM-based bulk heterojunction solar cells

NASA Astrophysics Data System (ADS)

Ergete, Assegid; Sabir, Fedlu K.; Li, Yongfang; Yohannes, Teketel

2015-01-01

In this investigation, photovoltaic (PV) parameters improvements in poly[2,6-(4,4‧-bis(2-ethylhexyl)dithieno[3,2-b:2‧,3‧-d]silole)-alt-5,5‧-(3,6-bis[4-(2-ethylhexyl)thienyl-2-yl]-s-tetrazine] and fullerene derivative [6,6]-phenyl-C61-butyric acid methyl ester (PDTSTTz:PCBM) blend were made through solvent additives and secondary donor addition. Short carbon chain solvent additives such as iodomethane (IMe), iodoethane (IEt), iodobutane (IBu), and diiodomethane (DIMe) were used. The results have shown that the short circuit current density (Jsc), as well as power conversion efficiency (PCE) of PDTSTTz:PCBM blend cell increased with the increase in length of carbon chains of the additives. IBu, with relatively the longest carbon chain, has better performance-improving impact than IMe (with the shortest carbon chain). The same trend was observed for fill factor. The other PV parameter, open circuit voltages (Voc), did not show significant change following these solvent additives. The effect of a secondary (additional) donor on the PDTSTTz/PCBM system was investigated by adding different proportions of poly(3-hexylthiophene-2,5-diyl) (P3HT). Because P3HT (secondary donor) and PDTSTTz (hosting donor) complement each other in light absorption, the PDTSTTz/PCBM system containing an optimum proportion of P3HT could provide a wider range of light absorption, and as a result it exhibited a higher short circuit current (11.08 mA/cm2) and then a PCE of 2.42%.

Single crystal growth in spin-coated films of polymorphic phthalocyanine derivative under solvent vapor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Higashi, T.; Ohmori, M.; Ramananarivo, M. F.

2015-12-01

The effects of solvent vapor on spin-coated films of a polymorphic phthalocyanine derivative were investigated. Growth of single crystal films via redissolving organic films under solvent vapor was revealed by in situ microscopic observations of the films. X-ray diffraction measurement of the films after exposing to solvent vapor revealed the phase transition of polymorphs under solvent vapor. The direction of crystal growth was clarified by measuring the crystal orientation in a grown monodomain film. The mechanism of crystal growth based on redissolving organic films under solvent vapor was discussed in terms of the different solubilities of the polymorphs.

Laser amplifier chain

DOEpatents

Hackel, R.P.

1992-10-20

A laser amplifier chain has a plurality of laser amplifiers arranged in a chain to sequentially amplify a low-power signal beam to produce a significantly higher-power output beam. Overall efficiency of such a chain is improved if high-gain, low efficiency amplifiers are placed on the upstream side of the chain where only a very small fraction of the total pumped power is received by the chain and low-gain, high-efficiency amplifiers are placed on the downstream side where a majority of pumping energy is received by the chain. 6 figs.

Comparison of the nutrient content of children's menu items at US restaurant chains, 2010-2014.

PubMed

Deierlein, Andrea L; Peat, Kay; Claudio, Luz

2015-08-15

To determine changes in the nutritional content of children's menu items at U.S. restaurant chains between 2010 and 2014. The sample consisted of 13 sit down and 16 fast-food restaurant chains ranked within the top 50 US chains in 2009. Nutritional information was accessed in June-July 2010 and 2014. Descriptive statistics were calculated for nutrient content of main dishes and side dishes, as well as for those items that were added, removed, or unchanged during the study period. Nutrient content of main dishes did not change significantly between 2010 and 2014. Approximately one-third of main dishes at fast-food restaurant chains and half of main dishes at sit down restaurant chains exceeded the 2010 Dietary Guidelines for Americans recommended levels for sodium, fat, and saturated fat in 2014. Improvements in nutrient content were observed for side dishes. At sit down restaurant chains, added side dishes contained over 50% less calories, fat, saturated fat, and sodium, and were more likely to contain fruits/vegetables compared to removed sides (p < 0.05 for all comparisons). Added side dishes at fast-food restaurant chains contained less saturated fat (p < 0.05). The majority of menu items, especially main dishes, available to children still contain high amounts of calories, fat, saturated fat, and sodium. Efforts must be made by the restaurant industry and policy makers to improve the nutritional content of children's menu items at restaurant chains to align with the Dietary Guidelines for Americans. Additional efforts are necessary to help parents and children make informed choices when ordering at restaurant chains.

In Vitro Enzymatic Synthesis of New Penicillins Containing Keto Acids as Side Chains

PubMed Central

Ferrero, Miguel A.; Reglero, Angel; Martínez-Blanco, Honorina; Fernández-Valverde, Martiniano; Luengo, Jose M.

1991-01-01

Seven different penicillins containing α-ketobutyric, β-ketobutyric, γ-ketovaleric, α-ketohexanoic, δ-ketohexanoic, ε-ketoheptanoic, and α-ketooctanoic acids as side chains have been synthesized in vitro by incubating the enzymes phenylacetyl coenzyme A (CoA) ligase from Pseudomonas putida and acyl-CoA:6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum with CoA, ATP, Mg2+, dithiothreitol, 6-aminopenicillanic acid, and the corresponding side chain precursor. PMID:1952871

[Study on anti-bacterium activity of ginkgolic acids and their momomers].

PubMed

Yang, Xiaoming; Zhu, Wei; Chen, Jun; Qian, Zhiyu; Xie, Jimin

2004-09-01

Ginkgolic acids and their three monomers were separated from ginkgo sarcotestas. The anti-bacterium activity of ginkgolic acids were tested. The relation between the anti-bacterium activity and side chain of ginkgolic acid were studied. The MIC of ginkgolic acids and their three monomers and salicylic acid were tested. Ginkgolic acid has strong inhibitive effect on G+-bacterium. Salicylic acid has no side chain, so no anti-bacterial activity. When the length of gingkolic acid side chain is C13:0, it has the strongest anti-bacterial activity in three monomers. The side chain of ginkgolic acid is the key functional group that possessed anti-bacterial activity. The length of Ginkgolic acid was the main effective factor of anti-bacterial activity.

Decomposition of total solvation energy into core, side-chains and water contributions: Role of cross correlations and protein conformational fluctuations in dynamics of hydration layer

NASA Astrophysics Data System (ADS)

Mondal, Sayantan; Mukherjee, Saumyak; Bagchi, Biman

2017-09-01

Dynamical coupling between water and amino acid side-chain residues in solvation dynamics is investigated by selecting residues often used as natural probes, namely tryptophan, tyrosine and histidine, located at different positions on protein surface. Such differently placed residues are found to exhibit different timescales of relaxation. The total solvation response measured by the probe is decomposed in terms of its interactions with (i) protein core, (ii) side-chain and (iii) water. Significant anti cross-correlation among these contributions are observed. When the motion of the protein side-chains is quenched, solvation either becomes faster or slower depending on the location of the probe.

Unfolding of globular polymers by external force

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bell, Samuel; Terentjev, Eugene M., E-mail: emt1000@cam.ac.uk

2015-11-14

We examine the problem of a polymer chain, folded into a globule in poor solvent, subjected to a constant tensile force. Such a situation represents a Gibbs thermodynamic ensemble and is useful for analysing force-clamp atomic force microscopy measurements, now very common in molecular biophysics. Using a basic Flory mean-field theory, we account for surface interactions of monomers with solvent. Under an increasing tensile force, a first-order phase transition occurs from a compact globule to a fully extended chain, in an “all-or-nothing” unfolding event. This contrasts with the regime of imposed extension, first studied by Halperin and Zhulina [Europhys. Lett.more » 15, 417 (1991)], where there is a regime of coexistence of a partial globule with an extended chain segment. We relate the transition forces in this problem to the solvent quality and degree of polymerisation, and also find analytical expressions for the energy barriers present in the problem. Using these expressions, we analyse the kinetic problem of a force-ramp experiment and show that the force at which a globule ruptures depends on the rate of loading.« less

Selective Template Wetting Routes to Hierarchical Polymer Films: Polymer Nanotubes from Phase-Separated Films via Solvent Annealing.

PubMed

Ko, Hao-Wen; Cheng, Ming-Hsiang; Chi, Mu-Huan; Chang, Chun-Wei; Chen, Jiun-Tai

2016-03-01

We demonstrate a novel wetting method to prepare hierarchical polymer films with polymer nanotubes on selective regions. This strategy is based on the selective wetting abilities of polymer chains, annealed in different solvent vapors, into the nanopores of porous templates. Phase-separated films of polystyrene (PS) and poly(methyl methacrylate) (PMMA), two commonly used polymers, are prepared as a model system. After anodic aluminum oxide (AAO) templates are placed on the films, the samples are annealed in vapors of acetic acid, in which the PMMA chains are swollen and wet the nanopores of the AAO templates selectively. As a result, hierarchical polymer films containing PMMA nanotubes can be obtained after the AAO templates are removed. The distribution of the PMMA nanotubes of the hierarchical polymer films can also be controlled by changing the compositions of the polymer blends. This work not only presents a novel method to fabricate hierarchical polymer films with polymer nanotubes on selective regions, but also gives a deeper understanding in the selective wetting ability of polymer chains in solvent vapors.

Improved packing of protein side chains with parallel ant colonies

PubMed Central

2014-01-01

Introduction The accurate packing of protein side chains is important for many computational biology problems, such as ab initio protein structure prediction, homology modelling, and protein design and ligand docking applications. Many of existing solutions are modelled as a computational optimisation problem. As well as the design of search algorithms, most solutions suffer from an inaccurate energy function for judging whether a prediction is good or bad. Even if the search has found the lowest energy, there is no certainty of obtaining the protein structures with correct side chains. Methods We present a side-chain modelling method, pacoPacker, which uses a parallel ant colony optimisation strategy based on sharing a single pheromone matrix. This parallel approach combines different sources of energy functions and generates protein side-chain conformations with the lowest energies jointly determined by the various energy functions. We further optimised the selected rotamers to construct subrotamer by rotamer minimisation, which reasonably improved the discreteness of the rotamer library. Results We focused on improving the accuracy of side-chain conformation prediction. For a testing set of 442 proteins, 87.19% of X1 and 77.11% of X12 angles were predicted correctly within 40° of the X-ray positions. We compared the accuracy of pacoPacker with state-of-the-art methods, such as CIS-RR and SCWRL4. We analysed the results from different perspectives, in terms of protein chain and individual residues. In this comprehensive benchmark testing, 51.5% of proteins within a length of 400 amino acids predicted by pacoPacker were superior to the results of CIS-RR and SCWRL4 simultaneously. Finally, we also showed the advantage of using the subrotamers strategy. All results confirmed that our parallel approach is competitive to state-of-the-art solutions for packing side chains. Conclusions This parallel approach combines various sources of searching intelligence and energy functions to pack protein side chains. It provides a frame-work for combining different inaccuracy/usefulness objective functions by designing parallel heuristic search algorithms. PMID:25474164

Exploration on effects of 15 nm SiO2 filler on miscibility, thermal stability and ionic conductivity of PMMA/ENR 50 electrolytes

NASA Astrophysics Data System (ADS)

Zamri, S. F. M.; Latif, F. A.; Ali, A. M. M.; Ibrahim, R.; Azuan, S. I. H. M.; Kamaluddin, N.; Hadip, F.

2017-02-01

The effects of silicon dioxide (SiO2) (15 nm) filler on miscibility, thermal stability and ionic conductivity of polymethyl methacrylate/50% epoxidized narural rubber (PMMA/ENR 50) electrolytes were successfully explored. Samples were prepared by solvent casting method with tetrahydrofuran (THF) as solvent and doped with lithium tetrafluoroborate (LiBF4). Fourier transform infrared spectroscopy (FTIR) confirmed the present of hydrogen bond between PMMA and ENR 50. However, the hydrogen bond was reduced when SiO2 was added. Differential scanning calorimeter (DSC) analysis shows that PMMA/ENR 50 blends exhibit two glass transition temperatures (Tgs) recorded at -35 and 89 °C corresponding to the Tg of ENR 50 rich phase (Tg1) and PMMA rich phase (Tg2), respectively. However, the two Tgs almost merging and reduced when SiO2 was added. Tg1 was found increases as SiO2 weight percent increased. Thermogravimetric analysis (TGA) revealed that thermal degradation temperatures (Tds) of SiO2 filled PMMA/ENR 50 was similar as PMMA/ENR 50. Interestingly, thermal degradation temperatures of the loss of impurities (Td1) and thermal degradation temperatures of PMMA side chain (Td2) were increased when SiO2 was added. Meanwhile thermal degradation temperatures of main PMMA and ENR 50 main chain (Td3) was decreased as SiO2 was added. There was no significant change in Td1, Td2 and Td3 as SiO2 weight percent was varied. Electrochemical impedence spectroscopy (EIS) analysis shows that room temperature ionic conductivity of SiO2 filled PMMA/ENR 50 electrolytes were higher compaed PMMA/ENR 50 electrolyte with two conductivity maxima.

Molecular description of the LCST behavior of an elastin-like polypeptide.

PubMed

Li, Nan K; García Quiroz, Felipe; Hall, Carol K; Chilkoti, Ashutosh; Yingling, Yaroslava G

2014-10-13

Elastin-like polypeptides (ELPs) with the repeat sequence of VPGVG are widely used as a model system for investigation of lower critical solution temperature (LCST) transition behavior. In this paper, the effect of temperature on the structure, dynamics and association of (VPGVG)18 in aqueous solution is investigated using atomistic molecular dynamics simulations. Our simulations show that as the temperature increases the ELP backbones undergo gradual conformational changes, which are attributed to the formation of more ordered secondary structures such as β-strands. In addition, increasing temperature changes the hydrophobicity of the ELP by exposure of hydrophobic valine-side chains to the solvent and hiding of proline residues. Based on our simulations, we conclude that the transition behavior of (VPGVG)18 can be attributed to a combination of thermal disruption of the water network that surrounds the polypeptide, reduction of solvent accessible surface area of the polypeptide, and increase in its hydrophobicity. Simulations of the association of two (VPGVG)18 molecules demonstrated that the observed gradual changes in the structural properties of the single polypeptide chain are enough to cause the aggregation of polypeptides above the LCST. These results lead us to propose that the LCST phase behavior of poly(VPGVG) is a collective phenomenon that originates from the correlated gradual changes in single polypeptide structure and the abrupt change in properties of hydration water around the peptide and is a result of a competition between peptide-peptide and peptide-water interactions. This is a computational study of an important intrinsically disordered peptide system that provides an atomic-level description of structural features and interactions that are relevant in the LCST phase behavior.

Exploring backbone-cation alkyl spacers for multi-cation side chain anion exchange membranes

NASA Astrophysics Data System (ADS)

Zhu, Liang; Yu, Xuedi; Hickner, Michael A.

2018-01-01

In order to systematically study how the arrangement of cations on the side chain and length of alkyl spacers between cations impact the performance of multi-cation AEMs for alkaline fuel cells, a series of polyphenylene oxide (PPO)-based AEMs with different cationic side chains were synthesized. This work resulted in samples with two or three cations in a side chain pendant to the PPO backbone. More importantly, the length of the spacer between cations varied from 3 methylene (-CH2-) (C3) groups to 8 methylene (C8) groups. The highest conductivity, up to 99 mS/cm in liquid water at room temperature, was observed for the triple-cation side chain AEM with pentyl (C5) or hexyl (C6) spacers. The multi-cation AEMs were found to have decreased water uptake and ionic conductivity when the spacer chains between cations were lengthened from pentyl (C5) or hexyl (C6) to octyl (C8) linking groups. The triple-cation membranes with pentyl (C5) or hexyl (C6) groups between cations showed greatest stability after immersion in 1 M NaOH at 80 °C for 500 h.

Handbook for Repairing Nonconventional Roofing Systems

DTIC Science & Technology

1988-12-01

membrane. 61 PIMB (solvent) Figure 71. Apply welding solvent to the PIB patch. Figure 72. Work the solvent Into the P113 patch. Pila 62 (solvent) Figure 73...when exposed to flame but will not burn nor support combustion . PVC repair techniques are basically the same as for a new application of a PVC fully...granules (if desired) before the final coat dries. 83 PUF F4gue 102. Remove the damaged material and bevel the s! des of the hole. 4󈧵, Figure 103. Trim th

Method for removing contaminants from plastic resin

DOEpatents

Bohnert, George W [Harrisonville, MO; Hand, Thomas E [Lee's Summit, MO; DeLaurentiis, Gary M [Jamestown, CA

2008-12-09

A resin recycling method that produces essentially contaminant-free synthetic resin material in an environmentally safe and economical manner. The method includes receiving the resin in container form. The containers are then ground into resin particles. The particles are exposed to a solvent, the solvent contacting the resin particles and substantially removing contaminants on the resin particles. After separating the particles and the resin, a solvent removing agent is used to remove any residual solvent remaining on the resin particles after separation.

29 CFR 1915.32 - Toxic cleaning solvents.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS FOR SHIPYARD EMPLOYMENT Surface Preparation and... or more of the following measures to safeguard the health of employees exposed to these solvents. (1...