Use of Molecular Dynamics for the Refinement of an Electrostatic Model for the In Silico Design of a Polymer Antidote for the Anticoagulant Fondaparinux

PubMed Central

Kwok, Ezra; Gopaluni, Bhushan; Kizhakkedathu, Jayachandran N.

2013-01-01

Molecular dynamics (MD) simulations results are herein incorporated into an electrostatic model used to determine the structure of an effective polymer-based antidote to the anticoagulant fondaparinux. In silico data for the polymer or its cationic binding groups has not, up to now, been available, and experimental data on the structure of the polymer-fondaparinux complex is extremely limited. Consequently, the task of optimizing the polymer structure is a daunting challenge. MD simulations provided a means to gain microscopic information on the interactions of the binding groups and fondaparinux that would have otherwise been inaccessible. This was used to refine the electrostatic model and improve the quantitative model predictions of binding affinity. Once refined, the model provided guidelines to improve electrostatic forces between candidate polymers and fondaparinux in order to increase association rate constants. PMID:27006916

Understanding and Manipulating Electrostatic Fields at the Protein-Protein Interface Using Vibrational Spectroscopy and Continuum Electrostatics Calculations.

PubMed

Ritchie, Andrew W; Webb, Lauren J

2015-11-05

Biological function emerges in large part from the interactions of biomacromolecules in the complex and dynamic environment of the living cell. For this reason, macromolecular interactions in biological systems are now a major focus of interest throughout the biochemical and biophysical communities. The affinity and specificity of macromolecular interactions are the result of both structural and electrostatic factors. Significant advances have been made in characterizing structural features of stable protein-protein interfaces through the techniques of modern structural biology, but much less is understood about how electrostatic factors promote and stabilize specific functional macromolecular interactions over all possible choices presented to a given molecule in a crowded environment. In this Feature Article, we describe how vibrational Stark effect (VSE) spectroscopy is being applied to measure electrostatic fields at protein-protein interfaces, focusing on measurements of guanosine triphosphate (GTP)-binding proteins of the Ras superfamily binding with structurally related but functionally distinct downstream effector proteins. In VSE spectroscopy, spectral shifts of a probe oscillator's energy are related directly to that probe's local electrostatic environment. By performing this experiment repeatedly throughout a protein-protein interface, an experimental map of measured electrostatic fields generated at that interface is determined. These data can be used to rationalize selective binding of similarly structured proteins in both in vitro and in vivo environments. Furthermore, these data can be used to compare to computational predictions of electrostatic fields to explore the level of simulation detail that is necessary to accurately predict our experimental findings.

The two sides of complement C3d: evolution of electrostatics in a link between innate and adaptive immunity.

PubMed

Kieslich, Chris A; Morikis, Dimitrios

2012-01-01

The interaction between complement fragment C3d and complement receptor 2 (CR2) is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor complex, including the C3d-CR2 interaction, is a much more recent adaptation. Human C3d and CR2 have net charges of -1 and +7 respectively, and are believed to have evolved favoring the role of electrostatics in their functions. To investigate the role of electrostatics in the function and evolution of human C3d and CR2, we have applied electrostatic similarity methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2. We also examine the effects of structural perturbation, as introduced through molecular dynamics and mutations, on spatial distributions of electrostatic potential to identify perturbation resistant regions, generated by so-called electrostatic "hot-spots". Distributions of electrostatic similarity based on families of perturbed structures illustrate the presence of electrostatic "hot-spots" at the two functional sites of C3d, while the surface of CR2 lacks electrostatic "hot-spots" despite its excessively positive nature. We propose that the electrostatic "hot-spots" of C3d have evolved to optimize its dual-functionality (covalently attaching to pathogen surfaces and interaction with CR2), which are both necessary for the formation B-cell co-receptor complexes. Comparison of the perturbation resistance of the electrostatic character of the homologues of C3d suggests that there was an emergence of a new role of electrostatics, and a transition in the function of C3d, after the divergence of jawless fish.

The Two Sides of Complement C3d: Evolution of Electrostatics in a Link between Innate and Adaptive Immunity

PubMed Central

Kieslich, Chris A.; Morikis, Dimitrios

2012-01-01

The interaction between complement fragment C3d and complement receptor 2 (CR2) is a key aspect of complement immune system activation, and is a component in a link between innate and adaptive immunities. The complement immune system is an ancient mechanism for defense, and can be found in species that have been on Earth for the last 600 million years. However, the link between the complement system and adaptive immunity, which is formed through the association of the B-cell co-receptor complex, including the C3d-CR2 interaction, is a much more recent adaptation. Human C3d and CR2 have net charges of −1 and +7 respectively, and are believed to have evolved favoring the role of electrostatics in their functions. To investigate the role of electrostatics in the function and evolution of human C3d and CR2, we have applied electrostatic similarity methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2. We also examine the effects of structural perturbation, as introduced through molecular dynamics and mutations, on spatial distributions of electrostatic potential to identify perturbation resistant regions, generated by so-called electrostatic “hot-spots”. Distributions of electrostatic similarity based on families of perturbed structures illustrate the presence of electrostatic “hot-spots” at the two functional sites of C3d, while the surface of CR2 lacks electrostatic “hot-spots” despite its excessively positive nature. We propose that the electrostatic “hot-spots” of C3d have evolved to optimize its dual-functionality (covalently attaching to pathogen surfaces and interaction with CR2), which are both necessary for the formation B-cell co-receptor complexes. Comparison of the perturbation resistance of the electrostatic character of the homologues of C3d suggests that there was an emergence of a new role of electrostatics, and a transition in the function of C3d, after the divergence of jawless fish. PMID:23300422

Electrostatics in protein–protein docking

PubMed Central

Heifetz, Alexander; Katchalski-Katzir, Ephraim; Eisenstein, Miriam

2002-01-01

A novel geometric-electrostatic docking algorithm is presented, which tests and quantifies the electrostatic complementarity of the molecular surfaces together with the shape complementarity. We represent each molecule to be docked as a grid of complex numbers, storing information regarding the shape of the molecule in the real part and information regarding the electrostatic character of the molecule in the imaginary part. The electrostatic descriptors are derived from the electrostatic potential of the molecule. Thus, the electrostatic character of the molecule is represented as patches of positive, neutral, or negative values. The potential for each molecule is calculated only once and stored as potential spheres adequate for exhaustive rotation/translation scans. The geometric-electrostatic docking algorithm is applied to 17 systems, starting form the structures of the unbound molecules. The results—in terms of the complementarity scores of the nearly correct solutions, their ranking in the lists of sorted solutions, and their statistical uniqueness—are compared with those of geometric docking, showing that the inclusion of electrostatic complementarity in docking is very important, in particular in docking of unbound structures. Based on our results, we formulate several "good electrostatic docking rules": The geometric-electrostatic docking procedure is more successful than geometric docking when the potential patches are large and when the potential extends away from the molecular surface and protrudes into the solvent. In contrast, geometric docking is recommended when the electrostatic potential around the molecules to be docked appears homogenous, that is, with a similar sign all around the molecule. PMID:11847280

Impact of electrostatics on the chemodynamics of highly charged metal-polymer nanoparticle complexes.

PubMed

Duval, Jérôme F L; Farinha, José Paulo S; Pinheiro, José P

2013-11-12

In this work, the impact of electrostatics on the stability constant, the rate of association/dissociation, and the lability of complexes formed between Cd(II), Pb(II), and carboxyl-modified polymer nanoparticles (also known as latex particles) of radius ∼ 50 nm is systematically investigated via electroanalytical measurements over a wide range of pHs and NaNO3 electrolyte concentrations. The corresponding interfacial structure and key electrostatic properties of the particles are independently derived from their electrokinetic response, successfully interpreted using soft particle electrohydrodynamic formalism, and complemented by Förster resonance energy transfer (FRET) analysis. The results underpin the presence of an ∼0.7-1 nm thick permeable and highly charged shell layer at the surface of the polymer nanoparticles. Their electrophoretic mobility further exhibits a minimum versus NaNO3 concentration due to strong polarization of the electric double layer. Integrating these structural and electrostatic particle features with recent theory on chemodynamics of particulate metal complexes yields a remarkable recovery of the measured increase in complex stability with increasing pH and/or decreasing solution salinity. In the case of the strongly binding Pb(II), the discrepancy at pH > 5.5 is unambiguously assigned to the formation of multidendate complexes with carboxylate groups located in the particle shell. With increasing pH and/or decreasing electrolyte concentration, the theory further predicts a kinetically controlled formation of metal complexes and a dramatic loss of their lability (especially for lead) on the time-scale of diffusion toward a macroscopic reactive electrode surface. These theoretical findings are again shown to be in agreement with experimental evidence.

Electrostatic design of protein-protein association rates.

PubMed

Schreiber, Gideon; Shaul, Yossi; Gottschalk, Kay E

2006-01-01

De novo design and redesign of proteins and protein complexes have made promising progress in recent years. Here, we give an overview of how to use available computer-based tools to design proteins to bind faster and tighter to their protein-complex partner by electrostatic optimization between the two proteins. Electrostatic optimization is possible because of the simple relation between the Debye-Huckel energy of interaction between a pair of proteins and their rate of association. This can be used for rapid, structure-based calculations of the electrostatic attraction between the two proteins in the complex. Using these principles, we developed two computer programs that predict the change in k(on), and as such the affinity, on introducing charged mutations. The two programs have a web interface that is available at www.weizmann.ac.il/home/bcges/PARE.html and http://bip.weizmann.ac.il/hypare. When mutations leading to charge optimization are introduced outside the physical binding site, the rate of dissociation is unchanged and therefore the change in k(on) parallels that of the affinity. This design method was evaluated on a number of different protein complexes resulting in binding rates and affinities of hundreds of fold faster and tighter compared to wild type. In this chapter, we demonstrate the procedure and go step by step over the methodology of using these programs for protein-association design. Finally, the way to easily implement the principle of electrostatic design for any protein complex of choice is shown.

Methylene blue binding to DNA with alternating AT base sequence: minor groove binding is favored over intercalation.

PubMed

Rohs, Remo; Sklenar, Heinz

2004-04-01

The results presented in this paper on methylene blue (MB) binding to DNA with AT alternating base sequence complement the data obtained in two former modeling studies of MB binding to GC alternating DNA. In the light of the large amount of experimental data for both systems, this theoretical study is focused on a detailed energetic analysis and comparison in order to understand their different behavior. Since experimental high-resolution structures of the complexes are not available, the analysis is based on energy minimized structural models of the complexes in different binding modes. For both sequences, four different intercalation structures and two models for MB binding in the minor and major groove have been proposed. Solvent electrostatic effects were included in the energetic analysis by using electrostatic continuum theory, and the dependence of MB binding on salt concentration was investigated by solving the non-linear Poisson-Boltzmann equation. We find that the relative stability of the different complexes is similar for the two sequences, in agreement with the interpretation of spectroscopic data. Subtle differences, however, are seen in energy decompositions and can be attributed to the change from symmetric 5'-YpR-3' intercalation to minor groove binding with increasing salt concentration, which is experimentally observed for the AT sequence at lower salt concentration than for the GC sequence. According to our results, this difference is due to the significantly lower non-electrostatic energy for the minor groove complex with AT alternating DNA, whereas the slightly lower binding energy to this sequence is caused by a higher deformation energy of DNA. The energetic data are in agreement with the conclusions derived from different spectroscopic studies and can also be structurally interpreted on the basis of the modeled complexes. The simple static modeling technique and the neglect of entropy terms and of non-electrostatic solute-solvent interactions, which are assumed to be nearly constant for the compared complexes of MB with DNA, seem to be justified by the results.

A Printing-Centric Approach to the Electrostatic Modification of Polymer/Clay Composites for use in 3D Direct-Ink Writing

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

Rauzan, Brittany; Lehman, Sean; McCracken, Josell

Polymer/clay composite inks are exceptionally useful materials for fabrication processes based on 3D direct-ink writing, however, there remains an insufficient understanding of how their physiochemical dynamics impact printability. Using a model system, N-isopropylacrylamide/Laponite, the electrostatic interactions between Laponite platelets are modified to tune critical rheological properties in order to improve printability. Rheological measurements and X-ray scattering experiments are carried out to monitor the nano/micro-structural dynamics and complex physicochemical interactions of Laponite as it impacts complex modulus in the linear region, flow behavior, thixotropy, and yield stress of the composite ink. Modification of the electrostatic interactions between platelets reduces the yieldmore » stress of the material, while maintaining a complex microstructure that allows for sufficient recovery times upon removal of stress to form stable, and thus printable, filaments. A printing-centric approach is established based on a fundamental understanding of electrostatic inter-particle interactions, harnessing the innate microstructure of Laponite in 3D direct-ink writing of composites.« less

Chromatin ionic atmosphere analyzed by a mesoscale electrostatic approach.

PubMed

Gan, Hin Hark; Schlick, Tamar

2010-10-20

Characterizing the ionic distribution around chromatin is important for understanding the electrostatic forces governing chromatin structure and function. Here we develop an electrostatic model to handle multivalent ions and compute the ionic distribution around a mesoscale chromatin model as a function of conformation, number of nucleosome cores, and ionic strength and species using Poisson-Boltzmann theory. This approach enables us to visualize and measure the complex patterns of counterion condensation around chromatin by examining ionic densities, free energies, shielding charges, and correlations of shielding charges around the nucleosome core and various oligonucleosome conformations. We show that: counterions, especially divalent cations, predominantly condense around the nucleosomal and linker DNA, unburied regions of histone tails, and exposed chromatin surfaces; ionic screening is sensitively influenced by local and global conformations, with a wide ranging net nucleosome core screening charge (56-100e); and screening charge correlations reveal conformational flexibility and interactions among chromatin subunits, especially between the histone tails and parental nucleosome cores. These results provide complementary and detailed views of ionic effects on chromatin structure for modest computational resources. The electrostatic model developed here is applicable to other coarse-grained macromolecular complexes. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Bimodal pair f-KdV dynamics in star-forming clouds

NASA Astrophysics Data System (ADS)

Karmakar, Pralay Kumar; Haloi, Archana; Roy, Supriya

2018-04-01

A theoretical formalism for investigating the bimodal conjugational mode dynamics of hybrid source, dictated by a unique pair of forced Korteweg-de Vries (f-KdV) equations in a complex turbo-magnetized star-forming cloud, is reported. It uses a standard multi-scale analysis executed over the cloud-governing equations in a closure form to derive the conjugated pair f-KdV system. We numerically see the structural features of two distinctive classes of eigenmode patterns stemming from the conjoint gravito-electrostatic interplay. The electrostatic compressive monotonic aperiodic shock-like patterns and gravitational compressive non-monotonic oscillatory shock-like structures are excitable. It is specifically revealed that the constitutive grain-charge (grain-mass) acts as electrostatic stabilizer (gravitational destabilizer) against the global cloud collapse dynamics. The basic features of the nonlinear coherent structures are confirmed in systematic phase-plane landscapes, indicating electrostatic irregular non-homoclinic open trajectories and gravitational atypical non-chaotic homoclinic fixed-point attractors. The relevance in the real astro-cosmic scenarios of the early phases of structure formation via wave-driven fluid-accretive transport processes is summarily emphasized.

Magnitude and nature of carbohydrate-aromatic interactions in fucose-phenol and fucose-indole complexes: CCSD(T) level interaction energy calculations.

PubMed

Tsuzuki, Seiji; Uchimaru, Tadafumi; Mikami, Masuhiro

2011-10-20

The CH/π contact structures of the fucose-phenol and fucose-indole complexes and the stabilization energies by formation of the complexes (E(form)) were studied by ab initio molecular orbital calculations. The three types of interactions (CH/π and OH/π interactions and OH/O hydrogen bonds) were compared and evaluated in a single molecular system and at the same level of theory. The E(form) calculated for the most stable CH/π contact structure of the fucose-phenol complex at the CCSD(T) level (-4.9 kcal/mol) is close to that for the most stable CH/π contact structure of the fucose-benzene complex (-4.5 kcal/mol). On the other hand the most stable CH/π contact structure of the fucose-indole complex has substantially larger E(form) (-6.5 kcal/mol). The dispersion interaction is the major source of the attraction in the CH/π contact structures of the fucose-phenol and fucose-indole complexes as in the case of the fucose-benzene complex. The electrostatic interactions in the CH/π contact structures are small (less than 1.5 kcal/mol). The nature of the interactions between the nonpolar surface of the carbohydrate and aromatic rings is completely different from that of the conventional hydrogen bonds where the electrostatic interaction is the major source of the attraction. The distributed multipole analysis and DFT-SATP analysis show that the dispersion interactions in the CH/π contact structure of fucose-indole complex are substantially larger than those in the CH/π contact structures of fucose-benzene and fucose-phenol complexes. The large dispersion interactions are responsible for the large E(form) for the fucose-indole complex.

In situ Investigation of Magnetism in Metastable Phases of Levitated Fe83 B17 During Solidification

NASA Astrophysics Data System (ADS)

Quirinale, D. G.; Messina, D.; Rustan, G. E.; Kreyssig, A.; Prozorov, R.; Goldman, A. I.

2017-11-01

In situ measurements of structure, density, and magnetization on samples of Fe83 B17 using an electrostatic levitation furnace allow us to identify and correlate the magnetic and structural transitions in this system during its complex solidification process. In particular, we identify magnetic ordering in the metastable Fe23 B6 /fcc Fe coherently grown structures and primitive tetragonal Fe3 B metastable phase in addition to characterizing the equilibrium Fe2 B phase. Our measurements demonstrate that the incorporation of a tunnel-diode oscillator circuit within an electrostatic levitation furnace enables investigations of the physical properties of high-temperature metastable structures.

Comparative density functional study of the complexes [UO2(CO3)3]4- and [(UO2)3(CO3)6]6- in aqueous solution.

PubMed

Schlosser, Florian; Moskaleva, Lyudmila V; Kremleva, Alena; Krüger, Sven; Rösch, Notker

2010-06-28

With a relativistic all-electron density functional method, we studied two anionic uranium(VI) carbonate complexes that are important for uranium speciation and transport in aqueous medium, the mononuclear tris(carbonato) complex [UO(2)(CO(3))(3)](4-) and the trinuclear hexa(carbonato) complex [(UO(2))(3)(CO(3))(6)](6-). Focusing on the structures in solution, we applied for the first time a full solvation treatment to these complexes. We approximated short-range effects by explicit aqua ligands and described long-range electrostatic interactions via a polarizable continuum model. Structures and vibrational frequencies of "gas-phase" models with explicit aqua ligands agree best with experiment. This is accidental because the continuum model of the solvent to some extent overestimates the electrostatic interactions of these highly anionic systems with the bulk solvent. The calculated free energy change when three mono-nuclear complexes associate to the trinuclear complex, agrees well with experiment and supports the formation of the latter species upon acidification of a uranyl carbonate solution.

eF-seek: prediction of the functional sites of proteins by searching for similar electrostatic potential and molecular surface shape.

PubMed

Kinoshita, Kengo; Murakami, Yoichi; Nakamura, Haruki

2007-07-01

We have developed a method to predict ligand-binding sites in a new protein structure by searching for similar binding sites in the Protein Data Bank (PDB). The similarities are measured according to the shapes of the molecular surfaces and their electrostatic potentials. A new web server, eF-seek, provides an interface to our search method. It simply requires a coordinate file in the PDB format, and generates a prediction result as a virtual complex structure, with the putative ligands in a PDB format file as the output. In addition, the predicted interacting interface is displayed to facilitate the examination of the virtual complex structure on our own applet viewer with the web browser (URL: http://eF-site.hgc.jp/eF-seek).

Vibrational Stark effect spectroscopy at the interface of Ras and Rap1A bound to the Ras binding domain of RalGDS reveals an electrostatic mechanism for protein-protein interaction.

PubMed

Stafford, Amy J; Ensign, Daniel L; Webb, Lauren J

2010-11-25

Electrostatic fields at the interface of the Ras binding domain of the protein Ral guanine nucleotide dissociation stimulator (RalGDS) with the structurally analogous GTPases Ras and Rap1A were measured with vibrational Stark effect (VSE) spectroscopy. Eleven residues on the surface of RalGDS that participate in this protein-protein interaction were systematically mutated to cysteine and subsequently converted to cyanocysteine in order to introduce a nitrile VSE probe in the form of the thiocyanate (SCN) functional group. The measured SCN absorption energy on the monomeric protein was compared with solvent-accessible surface area (SASA) calculations and solutions to the Poisson-Boltzmann equation using Boltzmann-weighted structural snapshots from molecular dynamics simulations. We found a weak negative correlation between SASA and measured absorption energy, indicating that water exposure of protein surface amino acids can be estimated from experimental measurement of the magnitude of the thiocyanate absorption energy. We found no correlation between calculated field and measured absorption energy. These results highlight the complex structural and electrostatic nature of the protein-water interface. The SCN-labeled RalGDS was incubated with either wild-type Ras or wild-type Rap1A, and the formation of the docked complex was confirmed by measurement of the dissociation constant of the interaction. The change in absorption energy of the thiocyanate functional group due to complex formation was related to the change in electrostatic field experienced by the nitrile functional group when the protein-protein interface forms. At some locations, the nitrile experiences the same shift in field when bound to Ras and Rap1A, but at others, the change in field is dramatically different. These differences identify residues on the surface of RalGDS that direct the specificity of RalGDS binding to its in vivo binding partner, Rap1A, through an electrostatic mechanism.

Investigating protein-protein interaction surfaces using a reduced stereochemical and electrostatic model.

PubMed

Warwicker, J

1989-03-20

A method of calculating the electrostatic potential energy between two molecules, using finite difference potential, is presented. A reduced charge set is used so that the interaction energy can be calculated as the two static molecules explore their full six-dimensional configurational space. The energies are contoured over surfaces fixed to each molecule with an interactive computer graphics program. For two crystal structures (trypsin-trypsin inhibitor and anti-lysozyme Fab-lysozyme), it is found that the complex corresponds to highly favourable interacting regions in the contour plots. These matches arise from a small number of protruding basic residues interacting with enhanced negative potential in each case. The redox pair cytochrome c peroxidase-cytochrome c exhibits an extensive favourably interacting surface within which a possible electron transfer complex may be defined by an increased electrostatic complementarity, but a decreased electrostatic energy. A possible substrate transfer configuration for the glycolytic enzyme pair glyceraldehyde phosphate dehydrogenase-phosphoglycerate kinase is presented.

Modeling the formation of ordered nano-assemblies comprised by dendrimers and linear polyelectrolytes: The role of Coulombic interactions

NASA Astrophysics Data System (ADS)

Eleftheriou, E.; Karatasos, K.

2012-10-01

Models of mixtures of peripherally charged dendrimers with oppositely charged linear polyelectrolytes in the presence of explicit solvent are studied by means of molecular dynamics simulations. Under the influence of varying strength of electrostatic interactions, these systems appear to form dynamically arrested film-like interconnected structures in the polymer-rich phase. Acting like a pseudo-thermodynamic inverse temperature, the increase of the strength of the Coulombic interactions drive the polymeric constituents of the mixture to a gradual dynamic freezing-in. The timescale of the average density fluctuations of the formed complexes initially increases in the weak electrostatic regime reaching a finite limit as the strength of electrostatic interactions grow. Although the models are overall electrically neutral, during this process the dendrimer/linear complexes develop a polar character with an excess charge mainly close to the periphery of the dendrimers. The morphological characteristics of the resulted pattern are found to depend on the size of the polymer chains on account of the distinct conformational features assumed by the complexed linear polyelectrolytes of different length. In addition, the length of the polymer chain appears to affect the dynamics of the counterions, thus affecting the ionic transport properties of the system. It appears, therefore, that the strength of electrostatic interactions together with the length of the linear polyelectrolytes are parameters to which these systems are particularly responsive, offering thus the possibility for a better control of the resulted structure and the electric properties of these soft-colloidal systems.

Electrostatic forces govern the binding mechanism of intrinsically disordered histone chaperones

PubMed Central

Liu, Chuanbo; Wang, Tianshu; Bai, Yawen; Wang, Jin

2017-01-01

A unified picture to understand the protein recognition and function must include the native binding complex structure ensembles and the underlying binding mechanisms involved in specific biological processes. However, quantifications of both binding complex structures and dynamical mechanisms are still challenging for IDP. In this study, we have investigated the underlying molecular mechanism of the chaperone Chz1 and histone H2A.Z-H2B association by equilibrium and kinetic stopped-flow fluorescence spectroscopy. The dependence of free energy and kinetic rate constant on electrolyte mean activity coefficient and urea concentration are uncovered. Our results indicate a previous unseen binding kinetic intermediate. An initial conformation selection step of Chz1 is also revealed before the formation of this intermediate state. Based on these observations, a mixed mechanism of three steps including both conformation selection and induced fit is proposed. By combination of the ion- and denaturant-induced experiments, we demonstrate that electrostatic forces play a dominant role in the recognition of bipolar charged intrinsically disordered protein Chz1 to its preferred partner H2A.Z-H2B. Both the intra-chain and inter-chain electrostatic interactions have direct impacts on the native collapsed structure and binding mechanism. PMID:28552960

In situ Investigation of Magnetism in Metastable Phases of Levitated Fe 83 B 17 During Solidification

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

Quirinale, D. G.; Messina, D.; Rustan, G. E.

In situ measurements of structure, density, and magnetization on samples of Fe 83 B 17 using an electrostatic levitation furnace allow us to identify and correlate the magnetic and structural transitions in this system during its complex solidification process. In particular, we identify magnetic ordering in the metastable Fe 23 B 6 / fcc Fe coherently grown structures and primitive tetragonal Fe 3 B metastable phase in addition to characterizing the equilibrium Fe 2 B phase. Our measurements demonstrate that the incorporation of a tunnel-diode oscillator circuit within an electrostatic levitation furnace enables investigations of the physical properties of high-temperaturemore » metastable structures.« less

The role of surface electrostatics on the stability, function and regulation of human cystathionine β-synthase, a complex multidomain and oligomeric protein.

PubMed

Pey, Angel L; Majtan, Tomas; Kraus, Jan P

2014-09-01

Human cystathionine β-synthase (hCBS) is a key enzyme of sulfur amino acid metabolism, controlling the commitment of homocysteine to the transsulfuration pathway and antioxidant defense. Mutations in hCBS cause inherited homocystinuria (HCU), a rare inborn error of metabolism characterized by accumulation of toxic homocysteine in blood and urine. hCBS is a complex multidomain and oligomeric protein whose activity and stability are independently regulated by the binding of S-adenosyl-methionine (SAM) to two different types of sites at its C-terminal regulatory domain. Here we study the role of surface electrostatics on the complex regulation and stability of hCBS using biophysical and biochemical procedures. We show that the kinetic stability of the catalytic and regulatory domains is significantly affected by the modulation of surface electrostatics through noticeable structural and energetic changes along their denaturation pathways. We also show that surface electrostatics strongly affect SAM binding properties to those sites responsible for either enzyme activation or kinetic stabilization. Our results provide new insight into the regulation of hCBS activity and stability in vivo with implications for understanding HCU as a conformational disease. We also lend experimental support to the role of electrostatic interactions in the recently proposed binding modes of SAM leading to hCBS activation and kinetic stabilization. Copyright © 2014 Elsevier B.V. All rights reserved.

SIRAH: a structurally unbiased coarse-grained force field for proteins with aqueous solvation and long-range electrostatics.

PubMed

Darré, Leonardo; Machado, Matías Rodrigo; Brandner, Astrid Febe; González, Humberto Carlos; Ferreira, Sebastián; Pantano, Sergio

2015-02-10

Modeling of macromolecular structures and interactions represents an important challenge for computational biology, involving different time and length scales. However, this task can be facilitated through the use of coarse-grained (CG) models, which reduce the number of degrees of freedom and allow efficient exploration of complex conformational spaces. This article presents a new CG protein model named SIRAH, developed to work with explicit solvent and to capture sequence, temperature, and ionic strength effects in a topologically unbiased manner. SIRAH is implemented in GROMACS, and interactions are calculated using a standard pairwise Hamiltonian for classical molecular dynamics simulations. We present a set of simulations that test the capability of SIRAH to produce a qualitatively correct solvation on different amino acids, hydrophilic/hydrophobic interactions, and long-range electrostatic recognition leading to spontaneous association of unstructured peptides and stable structures of single polypeptides and protein-protein complexes.

Exploring the Molecular Design of Protein Interaction Sites with Molecular Dynamics Simulations and Free Energy Calculations†

PubMed Central

Liang, Shide; Li, Liwei; Hsu, Wei-Lun; Pilcher, Meaghan N.; Uversky, Vladimir; Zhou, Yaoqi; Dunker, A. Keith; Meroueh, Samy O.

2009-01-01

The significant work that has been invested toward understanding protein–protein interaction has not translated into significant advances in structure-based predictions. In particular redesigning protein surfaces to bind to unrelated receptors remains a challenge, partly due to receptor flexibility, which is often neglected in these efforts. In this work, we computationally graft the binding epitope of various small proteins obtained from the RCSB database to bind to barnase, lysozyme, and trypsin using a previously derived and validated algorithm. In an effort to probe the protein complexes in a realistic environment, all native and designer complexes were subjected to a total of nearly 400 ns of explicit-solvent molecular dynamics (MD) simulation. The MD data led to an unexpected observation: some of the designer complexes were highly unstable and decomposed during the trajectories. In contrast, the native and a number of designer complexes remained consistently stable. The unstable conformers provided us with a unique opportunity to define the structural and energetic factors that lead to unproductive protein–protein complexes. To that end we used free energy calculations following the MM-PBSA approach to determine the role of nonpolar effects, electrostatics and entropy in binding. Remarkably, we found that a majority of unstable complexes exhibited more favorable electrostatics than native or stable designer complexes, suggesting that favorable electrostatic interactions are not prerequisite for complex formation between proteins. However, nonpolar effects remained consistently more favorable in native and stable designer complexes reinforcing the importance of hydrophobic effects in protein–protein binding. While entropy systematically opposed binding in all cases, there was no observed trend in the entropy difference between native and designer complexes. A series of alanine scanning mutations of hot-spot residues at the interface of native and designer complexes showed less than optimal contacts of hot-spot residues with their surroundings in the unstable conformers, resulting in more favorable entropy for these complexes. Finally, disorder predictions revealed that secondary structures at the interface of unstable complexes exhibited greater disorder than the stable complexes. PMID:19113835

DelPhi Web Server: A comprehensive online suite for electrostatic calculations of biological macromolecules and their complexes

PubMed Central

Sarkar, Subhra; Witham, Shawn; Zhang, Jie; Zhenirovskyy, Maxim; Rocchia, Walter; Alexov, Emil

2011-01-01

Here we report a web server, the DelPhi web server, which utilizes DelPhi program to calculate electrostatic energies and the corresponding electrostatic potential and ionic distributions, and dielectric map. The server provides extra services to fix structural defects, as missing atoms in the structural file and allows for generation of missing hydrogen atoms. The hydrogen placement and the corresponding DelPhi calculations can be done with user selected force field parameters being either Charmm22, Amber98 or OPLS. Upon completion of the calculations, the user is given option to download fixed and protonated structural file, together with the parameter and Delphi output files for further analysis. Utilizing Jmol viewer, the user can see the corresponding structural file, to manipulate it and to change the presentation. In addition, if the potential map is requested to be calculated, the potential can be mapped onto the molecule surface. The DelPhi web server is available from http://compbio.clemson.edu/delphi_webserver. PMID:24683424

Phase behaviour and structure of stable complexes of oppositely charged polyelectrolytes

NASA Astrophysics Data System (ADS)

Mengarelli, V.; Auvray, L.; Zeghal, M.

2009-03-01

We study the formation and structure of stable electrostatic complexes between oppositely charged polyelectrolytes, a long polymethacrylic acid and a shorter polyethylenimine, at low pH, where the polyacid is weakly charged. We explore the phase diagram as a function of the charge and concentration ratio of the constituents. In agreement with theory, turbidity and ζ potential measurements show two distinct regimes of weak and strong complexation, which appear successively as the pH is increased and are separated by a well-defined limit. Weak complexes observed by neutron scattering and contrast matching have an open, non-compact structure, while strong complexes are condensed.

An advanced application of the quantitative structure-activity relationship concept in electrokinetic chromatography of metal complexes.

PubMed

Oszwałdowski, Sławomir; Timerbaev, Andrei R

2008-02-01

The relevance of the quantitative structure-activity relationship (QSAR) principle in MEKC and microemulsion EKC (MEEKC) of metal-ligand complexes was evaluated for a better understanding of analyte migration mechanism. A series of gallium chelates were applied as test solutes with available experimental migration data in order to reveal the molecular properties that govern the separation. The QSAR models operating with n-octanol-water partition coefficients or van der Waals volumes were found to be valid for estimation of the retention factors (log k') of neutral compounds when using only an aqueous MEEKC electrolyte. On the other hand, consistent approximations of log k' for both uncharged and charged complexes in either EKC mode (and also with hydro-organic BGEs) were achievable with two-parametric QSARs in which the dipole moment is additionally incorporated as a structural descriptor, reflecting the electrostatic solute-pseudostationary phase interaction. The theoretical analysis of significant molecular parameters in MEKC systems, in which the micellar BGE is modified with an organic solvent, confirmed that concomitant consideration of hydrophobic, electrostatic, and solvation factors is essential for explaining the migration behavior of neutral metal complexes.

Structure of tropinone reductase-II complexed with NADP+ and pseudotropine at 1.9 A resolution: implication for stereospecific substrate binding and catalysis.

PubMed

Yamashita, A; Kato, H; Wakatsuki, S; Tomizaki, T; Nakatsu, T; Nakajima, K; Hashimoto, T; Yamada, Y; Oda, J

1999-06-15

Tropinone reductase-II (TR-II) catalyzes the NADPH-dependent reduction of the carbonyl group of tropinone to a beta-hydroxyl group. The crystal structure of TR-II complexed with NADP+ and pseudotropine (psi-tropine) has been determined at 1.9 A resolution. A seven-residue peptide near the active site, disordered in the unliganded structure, is fixed in the ternary complex by participation of the cofactor and substrate binding. The psi-tropine molecule is bound in an orientation which satisfies the product configuration and the stereochemical arrangement toward the cofactor. The substrate binding site displays a complementarity to the bound substrate (psi-tropine) in its correct orientation. In addition, electrostatic interactions between the substrate and Glu156 seem to specify the binding position and orientation of the substrate. A comparison between the active sites in TR-II and TR-I shows that they provide different van der Waals surfaces and electrostatic features. These differences likely contribute to the correct binding mode of the substrates, which are in opposite orientations in TR-II and TR-I, and to different reaction stereospecificities. The active site structure in the TR-II ternary complex also suggests that the arrangement of the substrate, cofactor, and catalytic residues is stereoelectronically favorable for the reaction.

Modeling uranium(VI) adsorption onto montmorillonite under varying carbonate concentrations: A surface complexation model accounting for the spillover effect on surface potential

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

Tournassat, C.; Tinnacher, R. M.; Grangeon, S.

The prediction of U(VI) adsorption onto montmorillonite clay is confounded by the complexities of: (1) the montmorillonite structure in terms of adsorption sites on basal and edge surfaces, and the complex interactions between the electrical double layers at these surfaces, and (2) U(VI) solution speciation, which can include cationic, anionic and neutral species. Previous U(VI)-montmorillonite adsorption and modeling studies have typically expanded classical surface complexation modeling approaches, initially developed for simple oxides, to include both cation exchange and surface complexation reactions. However, previous models have not taken into account the unique characteristics of electrostatic surface potentials that occur at montmorillonitemore » edge sites, where the electrostatic surface potential of basal plane cation exchange sites influences the surface potential of neighboring edge sites (‘spillover’ effect).« less

Modeling uranium(VI) adsorption onto montmorillonite under varying carbonate concentrations: A surface complexation model accounting for the spillover effect on surface potential

DOE PAGES

Tournassat, C.; Tinnacher, R. M.; Grangeon, S.; ...

2017-10-06

The prediction of U(VI) adsorption onto montmorillonite clay is confounded by the complexities of: (1) the montmorillonite structure in terms of adsorption sites on basal and edge surfaces, and the complex interactions between the electrical double layers at these surfaces, and (2) U(VI) solution speciation, which can include cationic, anionic and neutral species. Previous U(VI)-montmorillonite adsorption and modeling studies have typically expanded classical surface complexation modeling approaches, initially developed for simple oxides, to include both cation exchange and surface complexation reactions. However, previous models have not taken into account the unique characteristics of electrostatic surface potentials that occur at montmorillonitemore » edge sites, where the electrostatic surface potential of basal plane cation exchange sites influences the surface potential of neighboring edge sites (‘spillover’ effect).« less

The phase behavior of cationic lipid-DNA complexes.

PubMed Central

May, S; Harries, D; Ben-Shaul, A

2000-01-01

We present a theoretical analysis of the phase behavior of solutions containing DNA, cationic lipids, and nonionic (helper) lipids. Our model allows for five possible structures, treated as incompressible macroscopic phases: two lipid-DNA composite (lipoplex) phases, namely, the lamellar (L(alpha)(C)) and hexagonal (H(II)(C)) complexes; two binary (cationic/neutral) lipid phases, that is, the bilayer (L(alpha)) and inverse-hexagonal (H(II)) structures, and uncomplexed DNA. The free energy of the four lipid-containing phases is expressed as a sum of composition-dependent electrostatic, elastic, and mixing terms. The electrostatic free energies of all phases are calculated based on Poisson-Boltzmann theory. The phase diagram of the system is evaluated by minimizing the total free energy of the three-component mixture with respect to all the compositional degrees of freedom. We show that the phase behavior, in particular the preferred lipid-DNA complex geometry, is governed by a subtle interplay between the electrostatic, elastic, and mixing terms, which depend, in turn, on the lipid composition and lipid/DNA ratio. Detailed calculations are presented for three prototypical systems, exhibiting markedly different phase behaviors. The simplest mixture corresponds to a rigid planar membrane as the lipid source, in which case, only lamellar complexes appear in solution. When the membranes are "soft" (i.e., low bending modulus) the system exhibits the formation of both lamellar and hexagonal complexes, sometimes coexisting with each other, and with pure lipid or DNA phases. The last system corresponds to a lipid mixture involving helper lipids with strong propensity toward the inverse-hexagonal phase. Here, again, the phase diagram is rather complex, revealing a multitude of phase transitions and coexistences. Lamellar and hexagonal complexes appear, sometimes together, in different regions of the phase diagram. PMID:10733951

Protein-protein recognition: crystal structural analysis of a barnase-barstar complex at 2.0-A resolution.

PubMed

Buckle, A M; Schreiber, G; Fersht, A R

1994-08-02

We have solved, refined, and analyzed the 2.0-å resolution crystal structure of a 1:1 complex between the bacterial ribonuclease, barnase, and a Cys-->Ala(40,82) double mutant of its intracellular polypeptide inhibitor, barstar. Barstar inhibits barnase by sterically blocking the active site with a helix and adjacent loop segment. Almost half of the 14 hydrogen bonds between barnase and barstar involve two charged residues, and a third involve one charged partner. The electrostatic contribution to the overall binding energy is considerably greater than for other protein-protein interactions. Consequently, the very high rate constant for the barnase-barstar association (10(8) s-1 M-1) is most likely due to electrostatic steering effects. The barnase active-site residue His102 is located in a pocket on the surface of barstar, and its hydrogen bonds with Asp39 and Gly31 residues of barstar are directly responsible for the pH dependence of barnase-barstar binding. There is a high degree of complementarity both of the shape and of the charge of the interacting surfaces, but neither is perfect. The surface complementarity is slightly poorer than in protease-inhibitor complexes but a little better than in antibody-antigen interactions. However, since the burial of solvent in the barnase-barstar interface improves the fit significantly by filling in the majority of gaps, as well as stabilizing unfavorable electrostatic interactions, its role seems to be more important than in other protein-protein complexes. The electrostatic interactions between barnase and barstar are very similar to those between barnase and the tetranucleotide d(CGAC). In the barnase-barstar complex, the two phosphate-binding sites in the barnase active site are occupied by Asp39 and Gly43 of barstar. However, barstar has no equivalent for a guanine base of an RNA substrate, resulting in the occupation of the guanine recognition site in the barnase-barstar complex by nine ordered water molecules. Upon barnase-barstar binding, entropy losses resulting from the immobilization of segments of the protein chain and the energetic costs of conformational changes are minimized due to the essentially preformed active site of barnase. However, a certain degree of flexibility within the barnase active site is required to allow for the structural differences between barnase-barstar binding and barnase-RNA binding. A comparison between the bound and the free barstar structure shows that the overall structural response to barnase-binding is significant. This response can be best described as outwardly oriented, rigid-body movements of the four alpha-helices of barstar, resulting in the structure of bound barstar being somewhat expanded.

Temperature Controlled Electrostatic Disorder and Polymorphism in Ultrathin Films of α-Sexithiophene

NASA Astrophysics Data System (ADS)

Hoffman, Benjamin; Jafari, Sara; McAfee, Terry; Apperson, Aubrey; O'Connor, Brendan; Dougherty, Daniel

Competing phases in well-ordered alpha-sexithiophene (α-6T) are shown to contribute to electrostatic disorder observed by differences in surface potential between mono- and bi-layer crystallites. Ultrathin films are of key importance to devices in which charge transport occurs in the first several monolayers nearest to a dielectric interface (e.g. thin film transistors) and complex structures in this regime impact the general electrostatic landscape. This study is comprised of 1.5 ML sample crystals grown via organic molecular beam deposition onto a temperature controlled hexamethyldisilazane (HMDS) passivated SiO2 substrate to produce well-ordered layer-by-layer type growth. Sample topography and surface potential were characterized simultaneously using Kelvin Probe Force Microscopy to then isolate contact potential differences by first and second layer α-6T regions. Films grown on 70° C, 120° C substrates are observed to have a bilayer with lower, higher potential than the monolayer, respectively. Resulting interlayer potential differences are a clear source of electrostatic disorder and are explained as subtle shifts in tilt-angles between layers relative to the substrate. These empirical results continue our understanding of how co-existing orientations contribute to the complex electrostatics influencing charge transport. NSF CAREER award DMR-1056861.

Symmetry-adapted perturbation theory interaction energy decomposition for some noble gas complexes

NASA Astrophysics Data System (ADS)

Cukras, Janusz; Sadlej, Joanna

2008-06-01

This Letter contains a study of the interaction energy in HArF⋯N 2 and HArF⋯P 2 complexes. Symmetry-adapted perturbation theory (SAPT) has been applied to analyze the electrostatic, induction, dispersion and exchange contributions to the total interaction energy. The interaction energy has also been obtained by supermolecular method at the MP2, MP4, CCSD, CCSD(T) levels. The interaction energy for the studied complexes results from a partial cancelation of large attractive electrostatic, induction, dispersion terms by a strong repulsive exchange contribution. The induction and dispersion effects proved to be crucial in establishing the preference for the colinear HArF⋯N 2 and HArF⋯P 2 structures and shift direction of νHAr stretching vibrations.

Protein-ligand binding free energy estimation using molecular mechanics and continuum electrostatics. Application to HIV-1 protease inhibitors

NASA Astrophysics Data System (ADS)

Zoete, V.; Michielin, O.; Karplus, M.

2003-12-01

A method is proposed for the estimation of absolute binding free energy of interaction between proteins and ligands. Conformational sampling of the protein-ligand complex is performed by molecular dynamics (MD) in vacuo and the solvent effect is calculated a posteriori by solving the Poisson or the Poisson-Boltzmann equation for selected frames of the trajectory. The binding free energy is written as a linear combination of the buried surface upon complexation, SAS bur, the electrostatic interaction energy between the ligand and the protein, Eelec, and the difference of the solvation free energies of the complex and the isolated ligand and protein, ΔGsolv. The method uses the buried surface upon complexation to account for the non-polar contribution to the binding free energy because it is less sensitive to the details of the structure than the van der Waals interaction energy. The parameters of the method are developed for a training set of 16 HIV-1 protease-inhibitor complexes of known 3D structure. A correlation coefficient of 0.91 was obtained with an unsigned mean error of 0.8 kcal/mol. When applied to a set of 25 HIV-1 protease-inhibitor complexes of unknown 3D structures, the method provides a satisfactory correlation between the calculated binding free energy and the experimental pIC 50 without reparametrization.

VASP-E: Specificity Annotation with a Volumetric Analysis of Electrostatic Isopotentials

PubMed Central

Chen, Brian Y.

2014-01-01

Algorithms for comparing protein structure are frequently used for function annotation. By searching for subtle similarities among very different proteins, these algorithms can identify remote homologs with similar biological functions. In contrast, few comparison algorithms focus on specificity annotation, where the identification of subtle differences among very similar proteins can assist in finding small structural variations that create differences in binding specificity. Few specificity annotation methods consider electrostatic fields, which play a critical role in molecular recognition. To fill this gap, this paper describes VASP-E (Volumetric Analysis of Surface Properties with Electrostatics), a novel volumetric comparison tool based on the electrostatic comparison of protein-ligand and protein-protein binding sites. VASP-E exploits the central observation that three dimensional solids can be used to fully represent and compare both electrostatic isopotentials and molecular surfaces. With this integrated representation, VASP-E is able to dissect the electrostatic environments of protein-ligand and protein-protein binding interfaces, identifying individual amino acids that have an electrostatic influence on binding specificity. VASP-E was used to examine a nonredundant subset of the serine and cysteine proteases as well as the barnase-barstar and Rap1a-raf complexes. Based on amino acids established by various experimental studies to have an electrostatic influence on binding specificity, VASP-E identified electrostatically influential amino acids with 100% precision and 83.3% recall. We also show that VASP-E can accurately classify closely related ligand binding cavities into groups with different binding preferences. These results suggest that VASP-E should prove a useful tool for the characterization of specific binding and the engineering of binding preferences in proteins. PMID:25166865

Conceptual design and analysis of a large antenna utilizing electrostatic membrane management

NASA Technical Reports Server (NTRS)

Brooks, A. L.; Coyner, J. V.; Gardner, W. J.; Mihora, D. J.

1982-01-01

Conceptual designs and associated technologies for deployment 100 m class radiometer antennas were developed. An electrostatically suspended and controlled membrane mirror and the supporting structure are discussed. The integrated spacecraft including STS cargo bay stowage and development were analyzed. An antenna performance evaluation was performed as a measure of the quality of the membrane/spacecraft when used as a radiometer in the 1 GHz to 5 GHz region. Several related LSS structural dynamic models differing by their stiffness property (and therefore, lowest modal frequencies) are reported. Control system whose complexity varies inversely with increasing modal frequency regimes are also reported. Interactive computer-aided-design software is discussed.

Electrostatic Interactions in the Binding Pathway of a Transient Protein Complex Studied by NMR and Isothermal Titration Calorimetry*

PubMed Central

Meneses, Erick; Mittermaier, Anthony

2014-01-01

Much of our knowledge of protein binding pathways is derived from extremely stable complexes that interact very tightly, with lifetimes of hours to days. Much less is known about weaker interactions and transient complexes because these are challenging to characterize experimentally. Nevertheless, these types of interactions are ubiquitous in living systems. The combination of NMR relaxation dispersion Carr–Purcell–Meiboom–Gill (CPMG) experiments and isothermal titration calorimetry allows the quantification of rapid binding kinetics for complexes with submillisecond lifetimes that are difficult to study using conventional techniques. We have used this approach to investigate the binding pathway of the Src homology 3 (SH3) domain from the Fyn tyrosine kinase, which forms complexes with peptide targets whose lifetimes are on the order of about a millisecond. Long range electrostatic interactions have been shown to play a critical role in the binding pathways of tightly binding complexes. The role of electrostatics in the binding pathways of transient complexes is less well understood. Similarly to previously studied tight complexes, we find that SH3 domain association rates are enhanced by long range electrostatics, whereas short range interactions are formed late in the docking process. However, the extent of electrostatic association rate enhancement is several orders of magnitudes less, whereas the electrostatic-free basal association rate is significantly greater. Thus, the SH3 domain is far less reliant on electrostatic enhancement to achieve rapid association kinetics than are previously studied systems. This suggests that there may be overall differences in the role played by electrostatics in the binding pathways of extremely stable versus transient complexes. PMID:25122758

Primary role of the electrostatic contributions in a rational growth of hysteresis loop in spin-crossover Fe(II) complexes.

PubMed

Kepenekian, Mikaël; Le Guennic, Boris; Robert, Vincent

2009-08-19

We report a comprehensive analysis of the hysteresis behavior in a series of well-characterized spin-crossover Fe(II) materials. On the basis of the available X-ray data and multireference CASSCF (complete active space self-consistent field) calculations, we show that the growth of the hysteresis loop is controlled by electrostatic contributions. These environment effects turn out to be deeply modified as the crystal structure changes along the spin transition. Our theoretical inspection demonstrates the synergy between weak bonds and electrostatic interactions in the growth of hysteresis behavior. Quantitatively, it is suggested that the electrostatic contributions significantly enhance the cooperativity factor while weak bonds are determinant in the structuration of the 3D networks. Our picture does not rely on any parametrization but uses the microscopic information to derive an expression for the cooperativity parameter. The calculated values are in very good agreement with the experimental observations. Such inspection can thus be carried out to anticipate the hysteresis behavior of this intriguing class of materials.

Metal-ligand bond directionality in the M2-NH3 complexes (M = Cu, Ag and Au)

NASA Astrophysics Data System (ADS)

Eskandari, K.; Ebadinejad, F.

2018-05-01

The metal-ligand bonds in the M2-NH3 complexes (M = Au, Ag and Cu) are directional and the M-M-N angles tend to be linear. Natural energy decomposition analysis (NEDA) and localised molecular orbital energy decomposition analysis (LMOEDA) approaches indicate that the metal-ligand bonds in these complexes are mainly electrostatic in nature, however, the electrostatic is not the cause of the linearity of M-M-N arrangements. Instead, NEDA shows that the charge transfer and core repulsion are mainly responsible for the directionality of these bonds. In the LMOEDA point of view, the repulsion term is the main reason for the linearity of these complexes. Interacting quantum atoms (IQA) analysis shows that inter-atomic and inter-fragment interactions favour the nonlinear arrangements; however, these terms are compensated by the atomic self-energies, which stabilise the linear structure.

Electrostatic Interactions in Aminoglycoside-RNA Complexes

PubMed Central

Kulik, Marta; Goral, Anna M.; Jasiński, Maciej; Dominiak, Paulina M.; Trylska, Joanna

2015-01-01

Electrostatic interactions often play key roles in the recognition of small molecules by nucleic acids. An example is aminoglycoside antibiotics, which by binding to ribosomal RNA (rRNA) affect bacterial protein synthesis. These antibiotics remain one of the few valid treatments against hospital-acquired infections by Gram-negative bacteria. It is necessary to understand the amplitude of electrostatic interactions between aminoglycosides and their rRNA targets to introduce aminoglycoside modifications that would enhance their binding or to design new scaffolds. Here, we calculated the electrostatic energy of interactions and its per-ring contributions between aminoglycosides and their primary rRNA binding site. We applied either the methodology based on the exact potential multipole moment (EPMM) or classical molecular mechanics force field single-point partial charges with Coulomb formula. For EPMM, we first reconstructed the aspherical electron density of 12 aminoglycoside-RNA complexes from the atomic parameters deposited in the University at Buffalo Databank. The University at Buffalo Databank concept assumes transferability of electron density between atoms in chemically equivalent vicinities and allows reconstruction of the electron densities from experimental structural data. From the electron density, we then calculated the electrostatic energy of interaction using EPMM. Finally, we compared the two approaches. The calculated electrostatic interaction energies between various aminoglycosides and their binding sites correlate with experimentally obtained binding free energies. Based on the calculated energetic contributions of water molecules mediating the interactions between the antibiotic and rRNA, we suggest possible modifications that could enhance aminoglycoside binding affinity. PMID:25650932

Quantum chemical studies on hypothetical Fischer type Mo(CO)5[C(OEt)Me] and Mo(CO)5[C(OMe)Et] carbene complexes

NASA Astrophysics Data System (ADS)

Gövdeli, Nezafet; Karakaş, Duran

2018-07-01

Quantum chemical calculations at B3LYP/LANL2DZ/6-31G(d) level were made on anti-eclipsed, anti-staggered, syn-eclipsed, syn-staggered conformers of hypothetical Fischer type Mo(CO)5[C(OEt)Me] and Mo(CO)5[C(OMe)Et] carbene complexes in the gas phase. The most stable conformer of the complexes was found to be anti-staggered according to the total energy values calculated at given level. Structural parameters, vibration spectra, charge distributions, molecular orbital energy diagrams, contour diagrams of frontier orbitals, molecular electrostatic potential maps and some electronic structure descriptors were obtained for the most stable conformers. NMR spectra of the most stable conformers were calculated at GIAO/B3LYP/LANL2DZ level. The most stable conformer geometry was found to be distorted octahedral. IR and NMR spectra of the complexes are consistent with their geometry. HOMOs of the complexes were found to be center-atomic character and LUMOs were carbene-carbon character. From the calculated charge analysis and molecular electrostatic potential maps, it is found that carbene-carbon acts as electrofil and metal center nucleophile. It is suggested that the catalytic properties of the carbene complexes may be due to the fact that the carbene-carbon behave as electrophile and metal center nucleophile. Some electronic structure descriptors of the complexes were calculated and the molecular properties were estimated.

Identifying DNA-binding proteins using structural motifs and the electrostatic potential

PubMed Central

Shanahan, Hugh P.; Garcia, Mario A.; Jones, Susan; Thornton, Janet M.

2004-01-01

Robust methods to detect DNA-binding proteins from structures of unknown function are important for structural biology. This paper describes a method for identifying such proteins that (i) have a solvent accessible structural motif necessary for DNA-binding and (ii) a positive electrostatic potential in the region of the binding region. We focus on three structural motifs: helix–turn-helix (HTH), helix–hairpin–helix (HhH) and helix–loop–helix (HLH). We find that the combination of these variables detect 78% of proteins with an HTH motif, which is a substantial improvement over previous work based purely on structural templates and is comparable to more complex methods of identifying DNA-binding proteins. Similar true positive fractions are achieved for the HhH and HLH motifs. We see evidence of wide evolutionary diversity for DNA-binding proteins with an HTH motif, and much smaller diversity for those with an HhH or HLH motif. PMID:15356290

Polycation-sodium lauryl ether sulfate-type surfactant complexes: influence of ethylene oxide length.

PubMed

Vleugels, Leo F W; Pollet, Jennifer; Tuinier, Remco

2015-05-21

Polyelectrolyte-surfactant complexes (PESC) are a class of materials which form spontaneously by self-assembly driven by electrostatic and hydrophobic interactions. PESC containing sodium lauryl ether sulfates (SLES) have found wide application in hair care products like shampoo. Typically, SLES with only one or two ethylene oxide (EO) groups are used for this application. We have studied the influence of the size of the EO block (ranging from 0 to 30 EO groups) on complexation with two model polycations: linear polyDADMAC and branched PEI. PESC size and electrostatic properties were determined during stepwise titration of buffered polycation solutions. The critical aggregation concentration (CAC) of PESC was determined by surface tension measurements and fluorescence spectroscopy. For polyDADMAC, there is no influence of the size of the EO block on the complexation behavior; the stiff polycation governs the structure formation. For PEI, it was seen that the EO block size does affect the structure of the complexes. The CAC value of the investigated complexes turns out to be rather independent of the EO block size; however, the CMC/CAC ratio decreases with increasing size of the EO block. This latter observation explains why the Lochhead-Goddard effect is most effective for small EO blocks.

Effects of conformational ordering on protein/polyelectrolyte electrostatic complexation: ionic binding and chain stiffening

PubMed Central

Cao, Yiping; Fang, Yapeng; Nishinari, Katsuyoshi; Phillips, Glyn O.

2016-01-01

Coupling of electrostatic complexation with conformational transition is rather general in protein/polyelectrolyte interaction and has important implications in many biological processes and practical applications. This work studied the electrostatic complexation between κ-carrageenan (κ-car) and type B gelatin, and analyzed the effects of the conformational ordering of κ-car induced upon cooling in the presence of potassium chloride (KCl) or tetramethylammonium iodide (Me4NI). Experimental results showed that the effects of conformational ordering on protein/polyelectrolyte electrostatic complexation can be decomposed into ionic binding and chain stiffening. At the initial stage of conformational ordering, electrostatic complexation can be either suppressed or enhanced due to the ionic bindings of K+ and I− ions, which significantly alter the charge density of κ-car or occupy the binding sites of gelatin. Beyond a certain stage of conformational ordering, i.e., helix content θ > 0.30, the effect of chain stiffening, accompanied with a rapid increase in helix length ζ, becomes dominant and tends to dissociate the electrostatic complexation. The effect of chain stiffening can be theoretically interpreted in terms of double helix association. PMID:27030165

Tuning structure of oppositely charged nanoparticle and protein complexes

NASA Astrophysics Data System (ADS)

Kumar, Sugam; Aswal, V. K.; Callow, P.

2014-04-01

Small-angle neutron scattering (SANS) has been used to probe the structures of anionic silica nanoparticles (LS30) and cationic lyszyme protein (M.W. 14.7kD, I.P. ˜ 11.4) by tuning their interaction through the pH variation. The protein adsorption on nanoparticles is found to be increasing with pH and determined by the electrostatic attraction between two components as well as repulsion between protein molecules. We show the strong electrostatic attraction between nanoparticles and protein molecules leads to protein-mediated aggregation of nanoparticles which are characterized by fractal structures. At pH 5, the protein adsorption gives rise to nanoparticle aggregation having surface fractal morphology with close packing of nanoparticles. The surface fractals transform to open structures of mass fractal morphology at higher pH (7 and 9) on approaching isoelectric point (I.P.).

Reliable aluminum contact formation by electrostatic bonding

NASA Astrophysics Data System (ADS)

Kárpáti, T.; Pap, A. E.; Radnóczi, Gy; Beke, B.; Bársony, I.; Fürjes, P.

2015-07-01

The paper presents a detailed study of a reliable method developed for aluminum fusion wafer bonding assisted by the electrostatic force evolving during the anodic bonding process. The IC-compatible procedure described allows the parallel formation of electrical and mechanical contacts, facilitating a reliable packaging of electromechanical systems with backside electrical contacts. This fusion bonding method supports the fabrication of complex microelectromechanical systems (MEMS) and micro-opto-electromechanical systems (MOEMS) structures with enhanced temperature stability, which is crucial in mechanical sensor applications such as pressure or force sensors. Due to the applied electrical potential of  -1000 V the Al metal layers are compressed by electrostatic force, and at the bonding temperature of 450 °C intermetallic diffusion causes aluminum ions to migrate between metal layers.

Heteroprotein Complex Formation of Bovine Lactoferrin and Pea Protein Isolate: A Multiscale Structural Analysis.

PubMed

Adal, Eda; Sadeghpour, Amin; Connell, Simon; Rappolt, Michael; Ibanoglu, Esra; Sarkar, Anwesha

2017-02-13

Associative electrostatic interactions between two oppositely charged globular proteins, lactoferrin (LF) and pea protein isolate (PPI), the latter being a mixture of vicilin, legumin, and convicilin, was studied with a specific PPI/LF molar ratio at room temperature. Structural aspects of the electrostatic complexes probed at different length scales were investigated as a function of pH by means of different complementary techniques, namely, with dynamic light scattering, small-angle X-ray scattering (SAXS), turbidity measurements, and atomic force microscopy (AFM). Irrespective of the applied techniques, the results consistently displayed that complexation between LF and PPI did occur. In an optimum narrow range of pH 5.0-5.8, a viscous liquid phase of complex coacervate was obtained upon mild centrifugation of the turbid LF-PPI mixture with a maximum R h , turbidity and the ζ-potential being close to zero observed at pH 5.4. In particular, the SAXS data demonstrated that the coacervates were densely assembled with a roughly spherical size distribution exhibiting a maximum extension of ∼80 nm at pH 5.4. Equally, AFM image analysis showed size distributions containing most frequent cluster sizes around 40-80 nm with spherical to elliptical shapes (axis aspect ratio ≤ 2) as well as less frequent elongated to chainlike structures. The most frequently observed compact complexes, we identify as mainly leading to LF-PPI coacervation, whereas for the less frequent chain-like aggregates, we hypothesize that additionally PPI-PPI facilitated complexes exist.

Encapsulation of cisplatin as an anti-cancer drug into boron-nitride and carbon nanotubes: Molecular simulation and free energy calculation.

PubMed

Roosta, Sara; Hashemianzadeh, Seyed Majid; Ketabi, Sepideh

2016-10-01

Encapsulation of cisplatin anticancer drug into the single walled (10, 0) carbon nanotube and (10, 0) boron-nitride nanotube was investigated by quantum mechanical calculations and Monte Carlo Simulation in aqueous solution. Solvation free energies and complexation free energies of the cisplatin@ carbon nanotube and cisplatin@ boron-nitride nanotube complexes was determined as well as radial distribution functions of entitled compounds. Solvation free energies of cisplatin@ carbon nanotube and cisplatin@ boron-nitride nanotube were -4.128kcalmol(-1) and -2457.124kcalmol(-1) respectively. The results showed that cisplatin@ boron-nitride nanotube was more soluble species in water. In addition electrostatic contribution of the interaction of boron- nitride nanotube complex and solvent was -281.937kcalmol(-1) which really more than Van der Waals and so the electrostatic interactions play a distinctive role in the solvation free energies of boron- nitride nanotube compounds. On the other hand electrostatic part of the interaction of carbon nanotube complex and solvent were almost the same as Van der Waals contribution. Complexation free energies were also computed to study the stability of related structures and the free energies were negative (-374.082 and -245.766kcalmol(-1)) which confirmed encapsulation of drug into abovementioned nanotubes. However, boron-nitride nanotubes were more appropriate for encapsulation due to their larger solubility in aqueous solution. Copyright © 2016 Elsevier B.V. All rights reserved.

QM/MM hybrid calculation of biological macromolecules using a new interface program connecting QM and MM engines

NASA Astrophysics Data System (ADS)

Hagiwara, Yohsuke; Ohta, Takehiro; Tateno, Masaru

2009-02-01

An interface program connecting a quantum mechanics (QM) calculation engine, GAMESS, and a molecular mechanics (MM) calculation engine, AMBER, has been developed for QM/MM hybrid calculations. A protein-DNA complex is used as a test system to investigate the following two types of QM/MM schemes. In a 'subtractive' scheme, electrostatic interactions between QM/MM regions are truncated in QM calculations; in an 'additive' scheme, long-range electrostatic interactions within a cut-off distance from QM regions are introduced into one-electron integration terms of a QM Hamiltonian. In these calculations, 338 atoms are assigned as QM atoms using Hartree-Fock (HF)/density functional theory (DFT) hybrid all-electron calculations. By comparing the results of the additive and subtractive schemes, it is found that electronic structures are perturbed significantly by the introduction of MM partial charges surrounding QM regions, suggesting that biological processes occurring in functional sites are modulated by the surrounding structures. This also indicates that the effects of long-range electrostatic interactions involved in the QM Hamiltonian are crucial for accurate descriptions of electronic structures of biological macromolecules.

DelPhi webserver: Comprehensive suite for electrostatic calculations of biological macromolecules and their complexes

NASA Astrophysics Data System (ADS)

Witham, Shawn; Boylen, Brett; Owesen, Barr; Rocchia, Walter; Alexov, Emil

2011-03-01

Electrostatic forces and energies are two of the major components that contribute to the stability, function and interaction of biological macromolecules. The calculations of the electrostatic potential distribution in such systems, which are comprised of irregularly shaped objects immersed in a water phase, is not a trivial task. In addition, an accurate model requires any missing hydrogen atoms of the corresponding structural files (Protein Data Bank, or, PDB files) to be generated in silico and, if necessary, missing atoms or residues to be predicted as well. Here we report a comprehensive suite, an academic DelPhi webserver, which allows the users to upload their structural file, calculate the components of the electrostatic energy, generate the corresponding potential (and/or concentration/dielectric constant) distribution map, and choose the appropriate force field. The webserver utilizes modern technology to take user input and construct an algorithm that suits the users specific needs. The webserver uses Clemson University's Palmetto Supercomputer Cluster to handle the DelPhi calculations, which can range anywhere from small and short computation times, to extensive and computationally demanding runtimes. The work was supported by a grant from NIGMS, NIH, grant number 1R01GM093937-01.

Role of non-native electrostatic interactions in the coupled folding and binding of PUMA with Mcl-1

PubMed Central

Chu, Wen-Ting; Clarke, Jane; Shammas, Sarah L.; Wang, Jin

2017-01-01

PUMA, which belongs to the BH3-only protein family, is an intrinsically disordered protein (IDP). It binds to its cellular partner Mcl-1 through its BH3 motif, which folds upon binding into an α helix. We have applied a structure-based coarse-grained model, with an explicit Debye—Hückel charge model, to probe the importance of electrostatic interactions both in the early and the later stages of this model coupled folding and binding process. This model was carefully calibrated with the experimental data on helical content and affinity, and shown to be consistent with previously published experimental data on binding rate changes with respect to ionic strength. We find that intramolecular electrostatic interactions influence the unbound states of PUMA only marginally. Our results further suggest that intermolecular electrostatic interactions, and in particular non-native electrostatic interactions, are involved in formation of the initial encounter complex. We are able to reveal the binding mechanism in more detail than is possible using experimental data alone however, and in particular we uncover the role of non-native electrostatic interactions. We highlight the potential importance of such electrostatic interactions for describing the binding reactions of IDPs. Such approaches could be used to provide predictions for the results of mutational studies. PMID:28369057

Electrostatically Accelerated Encounter and Folding for Facile Recognition of Intrinsically Disordered Proteins

PubMed Central

Ganguly, Debabani; Zhang, Weihong; Chen, Jianhan

2013-01-01

Achieving facile specific recognition is essential for intrinsically disordered proteins (IDPs) that are involved in cellular signaling and regulation. Consideration of the physical time scales of protein folding and diffusion-limited protein-protein encounter has suggested that the frequent requirement of protein folding for specific IDP recognition could lead to kinetic bottlenecks. How IDPs overcome such potential kinetic bottlenecks to viably function in signaling and regulation in general is poorly understood. Our recent computational and experimental study of cell-cycle regulator p27 (Ganguly et al., J. Mol. Biol. (2012)) demonstrated that long-range electrostatic forces exerted on enriched charges of IDPs could accelerate protein-protein encounter via “electrostatic steering” and at the same time promote “folding-competent” encounter topologies to enhance the efficiency of IDP folding upon encounter. Here, we further investigated the coupled binding and folding mechanisms and the roles of electrostatic forces in the formation of three IDP complexes with more complex folded topologies. The surface electrostatic potentials of these complexes lack prominent features like those observed for the p27/Cdk2/cyclin A complex to directly suggest the ability of electrostatic forces to facilitate folding upon encounter. Nonetheless, similar electrostatically accelerated encounter and folding mechanisms were consistently predicted for all three complexes using topology-based coarse-grained simulations. Together with our previous analysis of charge distributions in known IDP complexes, our results support a prevalent role of electrostatic interactions in promoting efficient coupled binding and folding for facile specific recognition. These results also suggest that there is likely a co-evolution of IDP folded topology, charge characteristics, and coupled binding and folding mechanisms, driven at least partially by the need to achieve fast association kinetics for cellular signaling and regulation. PMID:24278008

Crystal structure of a designed, thermostable, heterotrimeric coiled coil.

PubMed Central

Nautiyal, S.; Alber, T.

1999-01-01

Electrostatic interactions are often critical for determining the specificity of protein-protein complexes. To study the role of electrostatic interactions for assembly of helical bundles, we previously designed a thermostable, heterotrimeric coiled coil, ABC, in which charged residues were employed to drive preferential association of three distinct, 34-residue helices. To investigate the basis for heterotrimer specificity, we have used multiwavelength anomalous diffraction (MAD) analysis to determine the 1.8 A resolution crystal structure of ABC. The structure shows that ABC forms a heterotrimeric coiled coil with the intended arrangement of parallel chains. Over half of the ion pairs engineered to restrict helix associations were apparent in the experimental electron density map. As seen in other trimeric coiled coils, ABC displays acute knobs-into-holes packing and a buried anion coordinated by core polar amino acids. These interactions validate the design strategy and illustrate how packing and polar contacts determine structural uniqueness. PMID:10210186

An Electrostatic Charge Partitioning Model for the Dissociation of Protein Complexes in the Gas Phase

NASA Astrophysics Data System (ADS)

Sciuto, Stephen V.; Liu, Jiangjiang; Konermann, Lars

2011-10-01

Electrosprayed multi-protein complexes can be dissociated by collisional activation in the gas phase. Typically, these processes follow a mechanism whereby a single subunit gets ejected with a disproportionately high amount of charge relative to its mass. This asymmetric behavior suggests that the departing subunit undergoes some degree of unfolding prior to being separated from the residual complex. These structural changes occur concomitantly with charge (proton) transfer towards the subunit that is being unraveled. Charge accumulation takes place up to the point where the subunit loses physical contact with the residual complex. This work develops a simple electrostatic model for studying the relationship between conformational changes and charge enrichment during collisional activation. Folded subunits are described as spheres that carry continuum surface charge. The unfolded chain is envisioned as random coil bead string. Simulations are guided by the principle that the system will adopt the charge configuration with the lowest potential energy for any backbone conformation. A finite-difference gradient algorithm is used to determine the charge on each subunit throughout the dissociation process. Both dimeric and tetrameric protein complexes are investigated. The model reproduces the occurrence of asymmetric charge partitioning for dissociation events that are preceded by subunit unfolding. Quantitative comparisons of experimental MS/MS data with model predictions yield estimates of the structural changes that occur during collisional activation. Our findings suggest that subunit separation can occur over a wide range of scission point structures that correspond to different degrees of unfolding.

The principle of minimal episteric distortion of the water matrix and its steering role in protein folding

NASA Astrophysics Data System (ADS)

Fernández, Ariel

2013-08-01

A significant episteric ("around a solid") distortion of the hydrogen-bond structure of water is promoted by solutes with nanoscale surface detail and physico-chemical complexity, such as soluble natural proteins. These structural distortions defy analysis because the discrete nature of the solvent at the interface is not upheld by the continuous laws of electrostatics. This work derives and validates an electrostatic equation that governs the episteric distortions of the hydrogen-bond matrix. The equation correlates distortions from bulk-like structural patterns with anomalous polarization components that do not align with the electrostatic field of the solute. The result implies that the interfacial energy stored in the orthogonal polarization correlates with the distortion of the water hydrogen-bond network. The result is validated vis-à-vis experimental data on protein interfacial thermodynamics and is interpreted in terms of the interaction energy between the electrostatic field of the solute and the dipole moment induced by the anomalous polarization of interfacial water. Finally, we consider solutes capable of changing their interface through conformational transitions and introduce a principle of minimal episteric distortion (MED) of the water matrix. We assess the importance of the MED principle in the context of protein folding, concluding that the native fold may be identified topologically with the conformation that minimizes the interfacial tension or disruption of the water matrix.

Conserved electrostatic fields at the Ras-effector interface measured through vibrational Stark effect spectroscopy explain the difference in tilt angle in the Ras binding domains of Raf and RalGDS.

PubMed

Walker, David M; Wang, Ruifei; Webb, Lauren J

2014-10-07

Vibrational Stark effect (VSE) spectroscopy was used to measure the electrostatic fields present at the interface of the human guanosine triphosphatase (GTPase) Ras docked with the Ras binding domain (RBD) of the protein kinase Raf. Nine amino acids located on the surface of Raf were selected for labeling with a nitrile vibrational probe. Eight of the probe locations were situated along the interface of Ras and Raf, and one probe was 2 nm away on the opposite side of Raf. Vibrational frequencies of the nine Raf nitrile probes were compared both in the monomeric, solvated protein and when docked with wild-type (WT) Ras to construct a comprehensive VSE map of the Ras-Raf interface. Molecular dynamics (MD) simulations employing an umbrella sampling strategy were used to generate a Boltzmann-weighted ensemble of nitrile positions in both the monomeric and docked complexes to determine the effect that docking has on probe location and orientation and to aid in the interpretation of VSE results. These results were compared to an identical study that was previously conducted on nine nitrile probes on the RBD of Ral guanidine dissociation stimulator (RalGDS) to make comparisons between the docked complexes formed when either of the two effectors bind to WT Ras. This comparison finds that there are three regions of conserved electrostatic fields that are formed upon docking of WT Ras with both downstream effectors. Conservation of this pattern in the docked complex then results in different binding orientations observed in otherwise structurally similar proteins. This work supports an electrostatic cause of the known binding tilt angle between the Ras-Raf and Ras-RalGDS complexes.

Axial iron coordination and spin state change in a heme c upon electrostatic protein-SAM interaction.

PubMed

Di Rocco, Giulia; Ranieri, Antonio; Bortolotti, Carlo Augusto; Battistuzzi, Gianantonio; Bonifacio, Alois; Sergo, Valter; Borsari, Marco; Sola, Marco

2013-08-28

A bacterial di-heme cytochrome c binds electrostatically to a gold electrode surface coated with a negatively charged COOH-terminated SAM adopting a sort of 'perpendicular' orientation. Cyclic voltammetry, Resonance Raman and SERRS spectroscopies indicate that the high-potential C-terminal heme center proximal to the SAM's surface undergoes an adsorption-induced swapping of one axial His ligand with a water molecule, which is probably lost in the reduced form, and a low- to high-spin transition. This coordination change for a bis-His ligated heme center upon an electrostatically-driven molecular recognition is as yet unprecedented, as well as the resulting increase in reduction potential. We discuss it in comparison with the known methionine ligand lability in monoheme cytochromes c occurring upon interaction with charged molecular patches. One possible implication of this finding in biological ET is that mobile redox partners do not behave as rigid and invariant bodies, but in the ET complex are subjected to molecular changes and structural fluctuations that affect in a complex way the thermodynamics and the kinetics of the process.

Self-assembly of polyelectrolyte surfactant complexes using large scale MD simulation

NASA Astrophysics Data System (ADS)

Goswami, Monojoy; Sumpter, Bobby

2014-03-01

Polyelectrolytes (PE) and surfactants are known to form interesting structures with varied properties in aqueous solutions. The morphological details of the PE-surfactant complexes depend on a combination of polymer backbone, electrostatic interactions and hydrophobic interactions. We study the self-assembly of cationic PE and anionic surfactants complexes in dilute condition. The importance of such complexes of PE with oppositely charged surfactants can be found in biological systems, such as immobilization of enzymes in polyelectrolyte complexes or nonspecific association of DNA with protein. Many useful properties of PE surfactant complexes come from the highly ordered structures of surfactant self-assembly inside the PE aggregate which has applications in industry. We do large scale molecular dynamics simulation using LAMMPS to understand the structure and dynamics of PE-surfactant systems. Our investigation shows highly ordered pearl-necklace structures that have been observed experimentally in biological systems. We investigate many different properties of PE-surfactant complexation for different parameter ranges that are useful for pharmaceutical, engineering and biological applications.

Sunitinib: from charge-density studies to interaction with proteins.

PubMed

Malińska, Maura; Jarzembska, Katarzyna N; Goral, Anna M; Kutner, Andrzej; Woźniak, Krzysztof; Dominiak, Paulina M

2014-05-01

Protein kinases are targets for the treatment of a number of diseases. Sunitinib malate is a type I inhibitor of tyrosine kinases and was approved as a drug in 2006. This contribution constitutes the first comprehensive analysis of the crystal structures of sunitinib malate and of complexes of sunitinib with a series of protein kinases. The high-resolution single-crystal X-ray measurement and aspherical atom databank approach served as a basis for reconstruction of the charge-density distribution of sunitinib and its protein complexes. Hirshfeld surface and topological analyses revealed a similar interaction pattern in the sunitinib malate crystal structure to that in the protein binding pockets. Sunitinib forms nine preserved bond paths corresponding to hydrogen bonds and also to the C-H···O and C-H···π contacts common to the VEGRF2, CDK2, G2, KIT and IT kinases. In general, sunitinib interacts with the studied proteins with a similar electrostatic interaction energy and can adjust its conformation to fit the binding pocket in such a way as to enhance the electrostatic interactions, e.g. hydrogen bonds in ligand-kinase complexes. Such behaviour may be responsible for the broad spectrum of action of sunitinib as a kinase inhibitor.

Structural basis of the inhibition of class C acid phosphatases by adenosine 5;#8242;-phosphorothioate

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

Singh, Harkewal; Reilly, Thomas J.; Tanner, John J.

2012-01-20

The inhibition of phosphatases by adenosine 5'-phosphorothioate (AMPS) was first reported in the late 1960s; however, the structural basis for the inhibition has remained unknown. Here, it is shown that AMPS is a submicromolar inhibitor of class C acid phosphatases, a group of bacterial outer membrane enzymes belonging to the haloacid dehalogenase structural superfamily. Furthermore, the 1.35-{angstrom} resolution crystal structure of the inhibited recombinant Haemophilus influenzae class C acid phosphatase was determined; this is the first structure of a phosphatase complexed with AMPS. The conformation of AMPS is identical to that of the substrate 5'-AMP, except that steric factors forcemore » a rotation of the thiophosphoryl out of the normal phosphoryl-binding pocket. This conformation is catalytically nonproductive, because the P atom is not positioned optimally for nucleophilic attack by Asp64, and the O atom of the scissile O-P bond is too far from the Asp (Asp66) that protonates the leaving group. The structure of 5'-AMP complexed with the Asp64 {yields} Asn mutant enzyme was also determined at 1.35-{angstrom} resolution. This mutation induces the substrate to adopt the same nonproductive binding mode that is observed in the AMPS complex. In this case, electrostatic considerations, rather than steric factors, underlie the movement of the phosphoryl. The structures not only provide an explanation for the inhibition by AMPS, but also highlight the precise steric and electrostatic requirements of phosphoryl recognition by class C acid phosphatases. Moreover, the structure of the Asp64 {yields} Asn mutant illustrates how a seemingly innocuous mutation can cause an unexpected structural change.« less

Electrostatic assembly of binary nanoparticle superlattices using protein cages

NASA Astrophysics Data System (ADS)

Kostiainen, Mauri A.; Hiekkataipale, Panu; Laiho, Ari; Lemieux, Vincent; Seitsonen, Jani; Ruokolainen, Janne; Ceci, Pierpaolo

2013-01-01

Binary nanoparticle superlattices are periodic nanostructures with lattice constants much shorter than the wavelength of light and could be used to prepare multifunctional metamaterials. Such superlattices are typically made from synthetic nanoparticles, and although biohybrid structures have been developed, incorporating biological building blocks into binary nanoparticle superlattices remains challenging. Protein-based nanocages provide a complex yet monodisperse and geometrically well-defined hollow cage that can be used to encapsulate different materials. Such protein cages have been used to program the self-assembly of encapsulated materials to form free-standing crystals and superlattices at interfaces or in solution. Here, we show that electrostatically patchy protein cages--cowpea chlorotic mottle virus and ferritin cages--can be used to direct the self-assembly of three-dimensional binary superlattices. The negatively charged cages can encapsulate RNA or superparamagnetic iron oxide nanoparticles, and the superlattices are formed through tunable electrostatic interactions with positively charged gold nanoparticles. Gold nanoparticles and viruses form an AB8fcc crystal structure that is not isostructural with any known atomic or molecular crystal structure and has previously been observed only with large colloidal polymer particles. Gold nanoparticles and empty or nanoparticle-loaded ferritin cages form an interpenetrating simple cubic AB structure (isostructural with CsCl). We also show that these magnetic assemblies provide contrast enhancement in magnetic resonance imaging.

Structural, spectral, NLO and MEP analysis of the [MgO2Ti2(OPri)6], [MgO2Ti2(OPri)2(acac)4] and [MgO2Ti2(OPri)2(bzac)4] by DFT method

NASA Astrophysics Data System (ADS)

Sayin, Koray; Karakaş, Duran

2015-06-01

Quantum chemical calculations are performed on [MgO2Ti2(OPri)6] and [MgO2Ti2(OPri)2(L)4] complexes. L is acetylacetonate (acac) and benzoylacetonate (bzac) anion. The crystal structures of these complexes have not been obtained as experimentally but optimized structures of these complexes are obtained as theoretically in this study. Universal force field (UFF) and DFT/B3LYP method are used to obtain optimized structures. Theoretical spectral analysis (IR, 1H and 13C NMR) is compared with their experimental values. A good agreement is found between experimental and theoretical spectral analysis. These results mean that the optimized structures of mentioned complexes are appropriate. Additionally, the active sites of mentioned complexes are determined by molecular electrostatic potential (MEP) diagrams and non-linear optical (NLO) properties are investigated.

Construction of Matryoshka-type structures from supercharged protein nanocages.

PubMed

Beck, Tobias; Tetter, Stephan; Künzle, Matthias; Hilvert, Donald

2015-01-12

Designing nanoscaled hierarchical structures with increasing levels of complexity is challenging. Here we show that electrostatic interactions between two complementarily supercharged protein nanocages can be effectively utilized to create nested Matryoshka-type structures. Cage-within-cage complexes containing spatially ordered iron oxide nanoparticles spontaneously self-assemble upon mixing positively supercharged ferritin compartments with AaLS-13, a larger shell-forming protein with a negatively supercharged lumen. Exploiting engineered Coulombic interactions and protein dynamics in this way opens up new avenues for creating hierarchically organized supramolecular assemblies for application as delivery vehicles, reaction chambers, and artificial organelles. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimization of binding electrostatics: Charge complementarity in the barnase-barstar protein complex

PubMed Central

lee, Lee-Peng; Tidor, Bruce

2001-01-01

Theoretical and experimental studies have shown that the large desolvation penalty required for polar and charged groups frequently precludes their involvement in electrostatic interactions that contribute strongly to net stability in the folding or binding of proteins in aqueous solution near room temperature. We have previously developed a theoretical framework for computing optimized electrostatic interactions and illustrated use of the algorithm with simplified geometries. Given a receptor and model assumptions, the method computes the ligand-charge distribution that provides the most favorable balance of desolvation and interaction effects on binding. In this paper the method has been extended to treat complexes using actual molecular shapes. The barnase-barstar protein complex was investigated with barnase treated as a target receptor. The atomic point charges of barstar were varied to optimize the electrostatic binding free energy. Barnase and natural barstar form a tight complex (Kd ∼ 10−14 M) with many charged and polar groups near the interface that make this a particularly relevant system for investigating the role of electrostatic effects on binding. The results show that sets of barstar charges (resulting from optimization with different constraints) can be found that give rise to relatively large predicted improvements in electrostatic binding free energy. Principles for enhancing the effect of electrostatic interactions in molecular binding in aqueous environments are discussed in light of the optima. Our findings suggest that, in general, the enhancements in electrostatic binding free energy resulting from modification of polar and charged groups can be substantial. Moreover, a recently proposed definition of electrostatic complementarity is shown to be a useful tool for examining binding interfaces. Finally, calculational results suggest that wild-type barstar is closer to being affinity optimized than is barnase for their mutual binding, consistent with the known roles of these proteins. PMID:11266622

Measurement of net electric charge and dipole moment of dust aggregates in a complex plasma.

PubMed

Yousefi, Razieh; Davis, Allen B; Carmona-Reyes, Jorge; Matthews, Lorin S; Hyde, Truell W

2014-09-01

Understanding the agglomeration of dust particles in complex plasmas requires knowledge of basic properties such as the net electrostatic charge and dipole moment of the dust. In this study, dust aggregates are formed from gold-coated mono-disperse spherical melamine-formaldehyde monomers in a radiofrequency (rf) argon discharge plasma. The behavior of observed dust aggregates is analyzed both by studying the particle trajectories and by employing computer models examining three-dimensional structures of aggregates and their interactions and rotations as induced by torques arising from their dipole moments. These allow the basic characteristics of the dust aggregates, such as the electrostatic charge and dipole moment, as well as the external electric field, to be determined. It is shown that the experimental results support the predicted values from computer models for aggregates in these environments.

Using complexation for the microencapsulation of nisin in biopolymer matrices by spray-drying.

PubMed

Ben Amara, Chedia; Kim, Lanhee; Oulahal, Nadia; Degraeve, Pascal; Gharsallaoui, Adem

2017-12-01

The aim of this study is to investigate the potential of complexation to encapsulate nisin (5g/L concentration) using spray-drying technique and to evaluate how complexation with pectin or alginate (2g/L concentration) can preserve nisin structure and antimicrobial activity. Spray-drying of nisin-low methoxyl pectin or nisin-alginate electrostatic complexes has led to the microencapsulation of the peptide in different networks that were highly influenced by the polysaccharide type. Turbidity and particle size measurements indicated that while spray-drying promoted the aggregation of nisin-pectin complexes, it favored the dissociation of nisin-alginate aggregates to form individual complexes. Structural changes of nisin induced by complexation with pectin or alginate and spray-drying were studied by using UV-Vis absorption and fluorescence spectroscopy. The results showed that complexation with pectin or alginate preserved nisin structure as well as its antimicrobial activity during spray-drying. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nanoporous Anodic Alumina Surface Modification by Electrostatic, Covalent, and Immune Complexation Binding Investigated by Capillary Filling.

PubMed

Eckstein, Chris; Acosta, Laura K; Pol, Laura; Xifré-Pérez, Elisabet; Pallares, Josep; Ferré-Borrull, Josep; Marsal, Lluis F

2018-03-28

The fluid imbibition-coupled laser interferometry (FICLI) technique has been applied to detect and quantify surface changes and pore dimension variations in nanoporous anodic alumina (NAA) structures. FICLI is a noninvasive optical technique that permits the determination of the NAA average pore radius with high accuracy. In this work, the technique is applied after each step of different surface modification paths of the NAA pores: (i) electrostatic immobilization of bovine serum albumin (BSA), (ii) covalent attachment of streptavidin via (3-aminipropyl)-triethoxysilane and glutaraldehyde grafting, and (iii) immune complexation. Results show that BSA attachment can be detected as a reduction in estimated radius from FICLI with high accuracy and reproducibility. In the case of the covalent attachment of streptavidin, FICLI is able to recognize a multilayer formation of the silane and the protein. For immune complexation, the technique is able to detect different antibody-antigen bindings and distinguish different dynamics among different immune species.

cDPD: A new dissipative particle dynamics method for modeling electrokinetic phenomena at the mesoscale

NASA Astrophysics Data System (ADS)

Deng, Mingge; Li, Zhen; Borodin, Oleg; Karniadakis, George Em

2016-10-01

We develop a "charged" dissipative particle dynamics (cDPD) model for simulating mesoscopic electrokinetic phenomena governed by the stochastic Poisson-Nernst-Planck and the Navier-Stokes equations. Specifically, the transport equations of ionic species are incorporated into the DPD framework by introducing extra degrees of freedom and corresponding evolution equations associated with each DPD particle. Diffusion of ionic species driven by the ionic concentration gradient, electrostatic potential gradient, and thermal fluctuations is captured accurately via pairwise fluxes between DPD particles. The electrostatic potential is obtained by solving the Poisson equation on the moving DPD particles iteratively at each time step. For charged surfaces in bounded systems, an effective boundary treatment methodology is developed for imposing both the correct hydrodynamic and electrokinetics boundary conditions in cDPD simulations. To validate the proposed cDPD model and the corresponding boundary conditions, we first study the electrostatic structure in the vicinity of a charged solid surface, i.e., we perform cDPD simulations of the electrostatic double layer and show that our results are in good agreement with the well-known mean-field theoretical solutions. We also simulate the electrostatic structure and capacity densities between charged parallel plates in salt solutions with different salt concentrations. Moreover, we employ the proposed methodology to study the electro-osmotic and electro-osmotic/pressure-driven flows in a micro-channel. In the latter case, we simulate the dilute poly-electrolyte solution drifting by electro-osmotic flow in a micro-channel, hence demonstrating the flexibility and capability of this method in studying complex fluids with electrostatic interactions at the micro- and nano-scales.

Modifications in structure and interaction of nanoparticle-protein-surfactant complexes in electrolyte solution

NASA Astrophysics Data System (ADS)

Mehan, Sumit; Kumar, S.; Aswal, V. K.; Schweins, R.

2016-05-01

SANS experiments of three-component system of anionic silica nanoparticles, anionic BSA protein and anionic SDS surfactants have been carried out without and with electrolyte in aqueous solution. In both the cases, the interaction of surfactant with protein results in formation of bead-necklace structure of protein-surfactant complexes in solution. These protein-surfactant complexes interact very differently with nanoparticles in absence and presence of electrolyte. In absence of electrolyte, nanoparticles remain in dispersed phase in solution, whereas with the addition of electrolyte the nanoparticles fractal aggregates are formed. SANS describes the phase behavior to be governed by competition of electrostatic and depletion interactions among the components solution.

Electrostatic Interactions between Elongated Monomers Drive Filamentation of Drosophila Shrub, a Metazoan ESCRT-III Protein.

PubMed

McMillan, Brian J; Tibbe, Christine; Jeon, Hyesung; Drabek, Andrew A; Klein, Thomas; Blacklow, Stephen C

2016-08-02

The endosomal sorting complex required for transport (ESCRT) is a conserved protein complex that facilitates budding and fission of membranes. It executes a key step in many cellular events, including cytokinesis and multi-vesicular body formation. The ESCRT-III protein Shrub in flies, or its homologs in yeast (Snf7) or humans (CHMP4B), is a critical polymerizing component of ESCRT-III needed to effect membrane fission. We report the structural basis for polymerization of Shrub and define a minimal region required for filament formation. The X-ray structure of the Shrub core shows that individual monomers in the lattice interact in a staggered arrangement using complementary electrostatic surfaces. Mutations that disrupt interface salt bridges interfere with Shrub polymerization and function. Despite substantial sequence divergence and differences in packing interactions, the arrangement of Shrub subunits in the polymer resembles that of Snf7 and other family homologs, suggesting that this intermolecular packing mechanism is shared among ESCRT-III proteins. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Holding the Nucleosome Together: A Quantitative Description of the DNA-Histone Interface in Solution.

PubMed

Elbahnsi, Ahmad; Retureau, Romain; Baaden, Marc; Hartmann, Brigitte; Oguey, Christophe

2018-02-13

The nucleosome is the fundamental unit of eukaryotic genome packaging in the chromatin. In this complex, the DNA wraps around eight histone proteins to form a superhelical double helix. The resulting bending, stronger than anything observed in free DNA, raises the question of how such a distortion is stabilized by the proteic and solvent environments. In this work, the DNA-histone interface in solution was exhaustively analyzed from nucleosome structures generated by molecular dynamics. An original Voronoi tessellation technique, measuring the topology of interacting elements without any empirical or subjective adjustment, was used to characterize the interface in terms of contact area and occurrence. Our results revealed an interface more robust than previously known, combining extensive, long-lived nonelectrostatic and electrostatic interactions between DNA and both structured and unstructured histone regions. Cation accumulation makes the proximity of juxtaposed DNA gyres in the superhelix possible by shielding the strong electrostatic repulsion of the charged phosphate groups. Overall, this study provides new insights on the nucleosome cohesion, explaining how DNA distortions can be maintained in a nucleoprotein complex.

Free energy decomposition of protein-protein interactions.

PubMed

Noskov, S Y; Lim, C

2001-08-01

A free energy decomposition scheme has been developed and tested on antibody-antigen and protease-inhibitor binding for which accurate experimental structures were available for both free and bound proteins. Using the x-ray coordinates of the free and bound proteins, the absolute binding free energy was computed assuming additivity of three well-defined, physical processes: desolvation of the x-ray structures, isomerization of the x-ray conformation to a nearby local minimum in the gas-phase, and subsequent noncovalent complex formation in the gas phase. This free energy scheme, together with the Generalized Born model for computing the electrostatic solvation free energy, yielded binding free energies in remarkable agreement with experimental data. Two assumptions commonly used in theoretical treatments; viz., the rigid-binding approximation (which assumes no conformational change upon complexation) and the neglect of vdW interactions, were found to yield large errors in the binding free energy. Protein-protein vdW and electrostatic interactions between complementary surfaces over a relatively large area (1400--1700 A(2)) were found to drive antibody-antigen and protease-inhibitor binding.

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

Romano, Keith P.; Laine, Jennifer M.; Deveau, Laura M.

Hepatitis C NS3/4A protease is a prime therapeutic target that is responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A, and 5A5B and two host cell adaptor proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host cell cleavage sites were determined and compared to the crystal structures of viral substrates. Two distinct protease conformations were observed and correlated with substrate specificity: (i) 3-4A, 4A4B, 5A5B, and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease, and (ii) TRIF andmore » 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes. These findings provide mechanistic insights into NS3/4A substrate recognition, which may assist in a more rational approach to inhibitor design in the face of the rapid acquisition of resistance.« less

Electrostatic study of Alanine mutational effects on transcription: application to GATA-3:DNA interaction complex.

PubMed

El-Assaad, Atlal; Dawy, Zaher; Nemer, Georges

2015-01-01

Protein-DNA interaction is of fundamental importance in molecular biology, playing roles in functions as diverse as DNA transcription, DNA structure formation, and DNA repair. Protein-DNA association is also important in medicine; understanding Protein-DNA binding kinetics can assist in identifying disease root causes which can contribute to drug development. In this perspective, this work focuses on the transcription process by the GATA Transcription Factor (TF). GATA TF binds to DNA promoter region represented by `G,A,T,A' nucleotides sequence, and initiates transcription of target genes. When proper regulation fails due to some mutations on the GATA TF protein sequence or on the DNA promoter sequence (weak promoter), deregulation of the target genes might lead to various disorders. In this study, we aim to understand the electrostatic mechanism behind GATA TF and DNA promoter interactions, in order to predict Protein-DNA binding in the presence of mutations, while elaborating on non-covalent binding kinetics. To generate a family of mutants for the GATA:DNA complex, we replaced every charged amino acid, one at a time, with a neutral amino acid like Alanine (Ala). We then applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations, for each mutation. These calculations delineate the contribution to binding from each Ala-replaced amino acid in the GATA:DNA interaction. After analyzing the obtained data in view of a two-step model, we are able to identify potential key amino acids in binding. Finally, we applied the model to GATA-3:DNA (crystal structure with PDB-ID: 3DFV) binding complex and validated it against experimental results from the literature.

On the Importance of Polar Interactions for Complexes Containing Intrinsically Disordered Proteins

PubMed Central

Wong, Eric T. C.; Na, Dokyun; Gsponer, Jörg

2013-01-01

There is a growing recognition for the importance of proteins with large intrinsically disordered (ID) segments in cell signaling and regulation. ID segments in these proteins often harbor regions that mediate molecular recognition. Coupled folding and binding of the recognition regions has been proposed to confer high specificity to interactions involving ID segments. However, researchers recently questioned the origin of the interaction specificity of ID proteins because of the overrepresentation of hydrophobic residues in their interaction interfaces. Here, we focused on the role of polar and charged residues in interactions mediated by ID segments. Making use of the extended nature of most ID segments when in complex with globular proteins, we first identified large numbers of complexes between globular proteins and ID segments by using radius-of-gyration-based selection criteria. Consistent with previous studies, we found the interfaces of these complexes to be enriched in hydrophobic residues, and that these residues contribute significantly to the stability of the interaction interface. However, our analyses also show that polar interactions play a larger role in these complexes than in structured protein complexes. Computational alanine scanning and salt-bridge analysis indicate that interfaces in ID complexes are highly complementary with respect to electrostatics, more so than interfaces of globular proteins. Follow-up calculations of the electrostatic contributions to the free energy of binding uncovered significantly stronger Coulombic interactions in complexes harbouring ID segments than in structured protein complexes. However, they are counter-balanced by even higher polar-desolvation penalties. We propose that polar interactions are a key contributing factor to the observed high specificity of ID segment-mediated interactions. PMID:23990768

Evidence for a ternary complex formed between flavodoxin and cytochrome c3: 1H-NMR and molecular modeling studies.

PubMed

Palma, P N; Moura, I; LeGall, J; Van Beeumen, J; Wampler, J E; Moura, J J

1994-05-31

Small electron-transfer proteins such as flavodoxin (16 kDa) and the tetraheme cytochrome c3 (13 kDa) have been used to mimic, in vitro, part of the complex electron-transfer chain operating between substrate electron donors and respiratory electron acceptors, in sulfate-reducing bacteria (Desulfovibrio species). The nature and properties of the complex formed between these proteins are revealed by 1H-NMR and molecular modeling approaches. Our previous study with the Desulfovibrio vulgaris proteins [Moura, I., Moura, J.J. G., Santos, M.H., & Xavier, A. V. (1980) Cienc. Biol. (Portugal) 5, 195-197; Stewart, D.E. LeGall, J., Moura, I., Moura, J. J. G., Peck, H.D. Jr., Xavier, A. V., Weiner, P. K., & Wampler, J.E. (1988) Biochemistry 27, 2444-2450] indicated that the complex between cytochrome c3 and flavodoxin could be monitored by changes in the NMR signals of the heme methyl groups of the cytochrome and that the electrostatic surface charge (Coulomb's law) on the two proteins favored interaction between one unique heme of the cytochrome with flavodoxin. If the interaction is indeed driven by the electrostatic complementarity between the acidic flavodoxin and a unique positive region of the cytochrome c3, other homologous proteins from these two families of proteins might be expected to interact similarly. In this study, three homologous Desulfovibrio cytochromes c3 were used, which show a remarkable variation in their individual isoelectric points (ranging from 5.5 to 9.5). On the basis of data obtained from protein-protein titrations followed at specific proton NMR signals (i.e., heme methyl resonances), a binding model for this complex has been developed with evaluation of stoichiometry and binding constants. This binding model involves one site on the cytochromes c3 and two sites on the flavodoxin, with formation of a ternary complex at saturation. In order to understand the potential chemical form of the binding model, a structural model for the hypothetical ternary complex, formed between one molecule of Desulfovibrio salexigens flavodoxin and two molecules of cytochrome c3, is proposed. These molecular models of the complexes were constructed on the basis of complementarity of Coulombic electrostatic surface potentials, using the available X-ray structures of the isolated proteins and, when required, model structures (D. salexigens flavodoxin and Desulfovibrio desulfuricans ATCC 27774 cytochrome c3) predicted by homology modeling.

The establishment and application of direct coupled electrostatic-structural field model in electrostatically controlled deployable membrane antenna

NASA Astrophysics Data System (ADS)

Gu, Yongzhen; Duan, Baoyan; Du, Jingli

2018-05-01

The electrostatically controlled deployable membrane antenna (ECDMA) is a promising space structure due to its low weight, large aperture and high precision characteristics. However, it is an extreme challenge to describe the coupled field between electrostatic and membrane structure accurately. A direct coupled method is applied to solve the coupled problem in this paper. Firstly, the membrane structure and electrostatic field are uniformly described by energy, considering the coupled problem is an energy conservation phenomenon. Then the direct coupled electrostatic-structural field governing equilibrium equations are obtained by energy variation approach. Numerical results show that the direct coupled method improves the computing efficiency by 36% compared with the traditional indirect coupled method with the same level accuracy. Finally, the prototype has been manufactured and tested and the ECDMA finite element simulations show good agreement with the experiment results as the maximum surface error difference is 6%.

A Method for the Calculation of Lattice Energies of Complex Crystals with Application to the Oxides of Molybdenum

NASA Technical Reports Server (NTRS)

Chaney, William S.

1961-01-01

A theoretical study has been made of molybdenum dioxide and molybdenum trioxide in order to extend the knowledge of factors Involved in the oxidation of molybdenum. New methods were developed for calculating the lattice energies based on electrostatic valence theory, and the coulombic, polarization, Van der Waals, and repulsion energie's were calculated. The crystal structure was examined and structure details were correlated with lattice energy.

Electrostatic interactions lead to the formation of asymmetric collagen-phosphophoryn aggregates.

PubMed

Dahl, Thomas; Veis, Arthur

2003-01-01

In bone and dentin the formation and mineralization of the extra cellular matrix structure is a complex process highly dependent on intermolecular interactions. In dentin, the phosphophoryns (PP) and type I collagen (COL1) are the major constituents implicated in mineralization. Thus, as a first step in understanding the tissue organization, we have initiated a study of their interaction as a function of pH, ionic strength, and relative concentrations or mixing ratios. Complex formation has been analyzed by dynamic light scattering to detect aggregate formation and by rotary shadowing electron microscopy (EM) to determine aggregate shape. The EM data showed that at the pH values studied, the PP-COL1 interaction leads to the formation of large fibrillar aggregates in which the PP are present along the fibril surfaces. The quantitative phase distribution data showed a 1/1 molar equivalence at the maximum aggregation point, not at electrostatic PP-COL1 equivalence. As the ionic strength was raised, the PP-COL1 aggregates became smaller but the binding and asymmetric fibrillar aggregation persisted. In EM, the PP appear as dense spheres. Along the surfaces of the collagen aggregates, the PP are larger and more open or extended, suggesting that COL1-bound PP may undergo a conformational change, opening up so that a single PP molecule might interact with and electrostatically link several COL1 molecules. This might have important implications for dentin structure, stability, and mineralization.

Nonlinear eigen-structures in star-forming gyratory nonthermal complex molecular clouds

NASA Astrophysics Data System (ADS)

Karmakar, Pralay Kumar; Dutta, Pranamika

2018-01-01

This paper deals with the nonlinear gravito-electrostatic fluctuations in star-forming rotating complex partially ionized dust molecular clouds, evolutionarily well-governed by a derived pair of the Korteweg-de Vries (KdV) equations of a unique analytical shape, in a bi-fluidic-model fabric. The lighter constituent species, such as electrons and ions, are considered thermo-statistically as the nonthermal ones in nature, governed by the anti-equilibrium kappa-distribution laws, due to inherent nonlocal gradient effects stemming from large-scale inhomogeneity. The heavier species, such as the constitutive identical neutral and charged dust micro-spheres, are treated as separate turbulent viscous fluids in the Larson logatropic tapestry. Application of a standard technique of multiple scale analysis over the nonlinearly perturbed cloud procedurally yields the pair KdV system. It comprises of the gravitational KdV and electrostatic KdV equations with exclusive constructs of diversified multi-parametric coefficients. A numerical constructive platform is provided to see the excitation and propagatory dynamics of gravitational rarefactive periodic soliton-trains and electrostatic rarefactive aperiodic damped soliton-trains of distinctive patterns as the pair-KdV-supported discrete coherent eigen-mode structures illustratively. The varied key stabilizing and tonality destabilizing factors behind the cloud dynamics are identified. An elaborated contrast of the eigen-mode conjugacy is reconnoitered. The main implications and applications of the semi-analytical results explored here are summarily outlined in the real astro-space-cosmic statuses.

Preparation, structure and analysis of the bonding in the molecular entity (OSO)2Li{[AlF(ORF)3]Li[Al(ORF)4]} (RF = C(CF3)3).

PubMed

Cameron, T Stanley; Nikiforov, Grigory B; Passmore, Jack; Rautiainen, J Mikko

2010-03-14

The (SO(2))(2)Li[AlF(OR(F))(3)]Li[Al(OR(F))(4)] (1) (R(F) = C(CF(3))(3)) molecular entity was obtained by thermal decomposition of Li[Al(OR(F))(4)] followed by crystallization from liquid SO(2). 1, containing two SO(2) molecules eta(1)-O coordinated to Li(+), was structurally characterized by single crystal X-ray diffraction and NMR spectroscopy in SO(2)(l). Bonding analyses of 1 (bond valency units, AIM analysis, atomic charges, bond orders) show that 1 can be either considered as a Li(OSO)(2)(+) complex stabilized by the large WCA [AlF(OR(F))(3)](-)Li(+)[Al(OR(F))(4)](-) or as consisting of 2 SO(2), 2 Li(+), [AlF(OR(F))(3)](-), and [Al(OR(F))(4)](-) joined by electrostatic interactions into the discrete molecular entity 1. The bonding between Li(+) and SO(2) molecules is shown to be almost completely attributable to monopole-induced dipole electrostatic interactions. Theoretical gas phase lithium ion affinity of SO(2) is determined to be stronger than its silver(I) ion affinity owing largely to the shorter lithium SO(2) contacts in the calculated structures that increase the electrostatic interaction.

A novel MEMS inertial switch with a reinforcing rib structure and electrostatic power assist to prolong the contact time

NASA Astrophysics Data System (ADS)

Li, Jian; Wang, Yan; Yang, Zhuoqing; Ding, Guifu; Zhao, Xiaolin; Wang, Hong

2018-03-01

The MEMS inertial switch is widely used in various industries owing to its advantage of small size, high integration, low power consumption and low costs, especially in the timing of Internet of things, such as toys, handheld devices, accessories and vibration testing. This paper provided a novel inertial switch with a reinforcing rib structure and electrostatic power assist. The designed inertial switch can reduce the complexity of the post-processing circuit and broaden its application prospect. The continuous electrostatic force can extend the contact time of the designed inertia switch before the leakage of electricity ends. The moving electrode with a reinforcing rib structure can effectively restrain the bending of the lower surface of moving electrode caused by residual stress. The array-type fixed electrode can ensure stable contact between the electrodes when the device is sensitive to external shocks. The dynamic displacement-time curve can be simulated by the COMSOL finite element simulation software. The laminated plating process is used to produce the designed inertial switch and the drop hammer acceleration monitoring system is used to test the fabricated device. The results indicate that, compared with the traditional design, the bouncing phenomenon can be prevented and extend the contact time to 336μs.

Electrostatic roles in electron transfer from [NiFe] hydrogenase to cytochrome c3 from Desulfovibrio vulgaris Miyazaki F.

PubMed

Sugimoto, Yu; Kitazumi, Yuki; Shirai, Osamu; Nishikawa, Koji; Higuchi, Yoshiki; Yamamoto, Masahiro; Kano, Kenji

2017-05-01

Electrostatic interactions between proteins are key factors that govern the association and reaction rate. We spectroscopically determine the second-order reaction rate constant (k) of electron transfer from [NiFe] hydrogenase (H 2 ase) to cytochrome (cyt) c 3 at various ionic strengths (I). The k value decreases with I. To analyze the results, we develop a semi-analytical formula for I dependence of k based on the assumptions that molecules are spherical and the reaction proceeds via a transition state. Fitting of the formula to the experimental data reveals that the interaction occurs in limited regions with opposite charges and with radii much smaller than those estimated from crystal structures. This suggests that local charges in H 2 ase and cyt c 3 play important roles in the reaction. Although the crystallographic data indicate a positive electrostatic potential over almost the entire surface of the proteins, there exists a small region with negative potential on H 2 ase at which the electron transfer from H 2 ase to cyt c 3 may occur. This local negative potential region is identical to the hypothetical interaction sphere predicted by the analysis. Furthermore, I dependence of k is predicted by the Adaptive Poisson-Boltzmann Solver considering all charges of the amino acids in the proteins and the configuration of H 2 ase/cyt c 3 complex. The calculation reproduces the experimental results except at extremely low I. These results indicate that the stabilization derived from the local electrostatic interaction in the H 2 ase/cyt c 3 complex overcomes the destabilization derived from the electrostatic repulsion of the overall positive charge of both proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

Interaction of DNA with Simple and Mixed Ligand Copper(II) Complexes of 1,10-Phenanthrolines as Studied by DNA-Fiber EPR Spectroscopy

PubMed Central

Chikira, Makoto; Ng, Chew Hee; Palaniandavar, Mallayan

2015-01-01

The interaction of simple and ternary Cu(II) complexes of 1,10-phenanthrolines with DNA has been studied extensively because of their various interesting and important functions such as DNA cleavage activity, cytotoxicity towards cancer cells, and DNA based asymmetric catalysis. Such functions are closely related to the DNA binding modes of the complexes such as intercalation, groove binding, and electrostatic surface binding. A variety of spectroscopic methods have been used to study the DNA binding mode of the Cu(II) complexes. Of all these methods, DNA-fiber electron paramagnetic resonance (EPR) spectroscopy affords unique information on the DNA binding structures of the complexes. In this review we summarize the results of our DNA-fiber EPR studies on the DNA binding structure of the complexes and discuss them together with the data accumulated by using other measurements. PMID:26402668

Dynamic torsional motion of a diruthenium complex with four homo-catecholates and first synthesis of a diruthenium complex with mixed-catecholates

NASA Astrophysics Data System (ADS)

Chang, Ho-Chol; Mochizuki, Katsunori; Kitagawa, Susumu

2008-11-01

Dynamic properties of a diruthenium complex with ligand-unsupported Ru-Ru triple bonds, Na 2[Ru 2(3,6-DTBCat) 4] ( 1), were studied using variable-temperature 1H NMR. Structural freedom derived from the ligand-unsupported structure leads to torsional motion about the Ru-Ru bonds in THF and in DMF. The observed solvent dependency corresponds to the electrostatic interactions between the diruthenium complex and Na + counter cations, which are sensitive to the polarity of solvents. In addition, a new diruthenium complex, [{Na(THF) 2(H 2O)}{Na(THF) 0.5(H 2O)}{Ru 2(3,6-DTBCat) 2(H 4Cat) 2}] ( 2·2.5THF·2H 2O), with a ligand-unsupported Ru-Ru bond surrounded by two different kinds of catecholate derivatives, has been synthesized and crystallographically characterized. The complex, which was characterized by single-crystal structural analysis, will provide an opportunity to investigate not only static molecular structures but also dynamic physicochemical properties in comparison with analogues containing four identical catecholate derivatives.

Influence of electric field on interwell tunneling rate in quasi two dimensional organic quantum wells

NASA Astrophysics Data System (ADS)

Donovan, K. J.; Elliott, J. E.; Jeong, I. S.; Scott, K.; Wilson, E. G.

2000-11-01

The tunneling rate of photocreated charge carriers between layers in Langmuir-Blodgett multilayer structures is measured indirectly using the novel technique of bimolecular recombination quenching. The tunneling rate is demonstrated to be dependent upon the applied electrostatic potential difference between the layers. This dependence is explored in light of the Marcus theory of charge transfer. That theory was developed to describe redox reactions where the driving force is supplied by a chemical potential difference between two chemically different parts of a more complex system. In the current work the electrostatic potential replaces the chemical potential as the driving potential. The field dependence of the exciton dissociation probability is also determined.

Optimization design combined with coupled structural-electrostatic analysis for the electrostatically controlled deployable membrane reflector

NASA Astrophysics Data System (ADS)

Liu, Chao; Yang, Guigeng; Zhang, Yiqun

2015-01-01

The electrostatically controlled deployable membrane reflector (ECDMR) is a promising scheme to construct large size and high precision space deployable reflector antennas. This paper presents a novel design method for the large size and small F/D ECDMR considering the coupled structure-electrostatic problem. First, the fully coupled structural-electrostatic system is described by a three field formulation, in which the structure and passive electrical field is modeled by finite element method, and the deformation of the electrostatic domain is predicted by a finite element formulation of a fictitious elastic structure. A residual formulation of the structural-electrostatic field finite element model is established and solved by Newton-Raphson method. The coupled structural-electrostatic analysis procedure is summarized. Then, with the aid of this coupled analysis procedure, an integrated optimization method of membrane shape accuracy and stress uniformity is proposed, which is divided into inner and outer iterative loops. The initial state of relatively high shape accuracy and uniform stress distribution is achieved by applying the uniform prestress on the membrane design shape and optimizing the voltages, in which the optimal voltage is computed by a sensitivity analysis. The shape accuracy is further improved by the iterative prestress modification using the reposition balance method. Finally, the results of the uncoupled and coupled methods are compared and the proposed optimization method is applied to design an ECDMR. The results validate the effectiveness of this proposed methods.

Formation of stable nanoparticles via electrostatic complexation between sodium caseinate and gum arabic.

PubMed

Ye, Aiqian; Flanagan, John; Singh, Harjinder

2006-06-05

The formation of electrostatic complexes between sodium caseinate and gum arabic (GA) was studied as a function of pH (2.0-7.0), using slow acidification in situ with glucono-delta-lactone (GDL) or titration with HCl. The colloidal behavior of the complexes under specific conditions was investigated using absorbance measurements (at 515 or 810 nm) and dynamic light scattering (DLS). In contrast to the sudden increase in absorbance and subsequent precipitation of sodium caseinate solutions at pH < 5.4, the absorbance values of mixtures of sodium caseinate and GA increased to a level that was dependent on GA concentration at pH 5.4 (pH(c)). The absorbance values remained constant with further decreases in pH until a sudden increase in absorbance was observed (at pH(phi)). The pH(phi) was also dependent upon the GA concentration. Dynamic light scattering (DLS) data showed that the sizes of the particles formed by the complexation of sodium caseinate and GA between pH(c) and pH(phi) were between 100 and 150 nm and these nanoparticles were visualized using negative staining transmission electron microscopy (TEM). Below pH(phi), the nanoparticles associated to form larger particles, causing phase separation. zeta-Potential measurements of the nanoparticles and chemical analysis after phase separation showed that phase separation was a consequence of charge neutralization. The formation of complexes between sodium caseinate and GA was inhibited at high ionic strength (>50 mM NaCl). It is postulated that the structure of the nanoparticles comprises an aggregated caseinate core, protected from further aggregation by steric repulsion of one, or more, electrostatically attached GA molecules. Copyright 2005 Wiley Periodicals, Inc.

Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold

PubMed Central

Huber, Roland G.; Bond, Peter J.

2017-01-01

An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners. PMID:29016650

Protein-protein interactions in paralogues: Electrostatics modulates specificity on a conserved steric scaffold.

PubMed

Ivanov, Stefan M; Cawley, Andrew; Huber, Roland G; Bond, Peter J; Warwicker, Jim

2017-01-01

An improved knowledge of protein-protein interactions is essential for better understanding of metabolic and signaling networks, and cellular function. Progress tends to be based on structure determination and predictions using known structures, along with computational methods based on evolutionary information or detailed atomistic descriptions. We hypothesized that for the case of interactions across a common interface, between proteins from a pair of paralogue families or within a family of paralogues, a relatively simple interface description could distinguish between binding and non-binding pairs. Using binding data for several systems, and large-scale comparative modeling based on known template complex structures, it is found that charge-charge interactions (for groups bearing net charge) are generally a better discriminant than buried non-polar surface. This is particularly the case for paralogue families that are less divergent, with more reliable comparative modeling. We suggest that electrostatic interactions are major determinants of specificity in such systems, an observation that could be used to predict binding partners.

Breakdown of the Debye polarization ansatz at protein-water interfaces

NASA Astrophysics Data System (ADS)

Fernández Stigliano, Ariel

2013-06-01

The topographical and physico-chemical complexity of protein-water interfaces scales down to the sub-nanoscale range. At this level of confinement, we demonstrate that the dielectric structure of interfacial water entails a breakdown of the Debye ansatz that postulates the alignment of polarization with the protein electrostatic field. The tendencies to promote anomalous polarization are determined for each residue type and a particular kind of structural defect is shown to provide the predominant causal context.

Using Programmable Calculators to Solve Electrostatics Problems.

ERIC Educational Resources Information Center

Yerian, Stephen C.; Denker, Dennis A.

1985-01-01

Provides a simple routine which allows first-year physics students to use programmable calculators to solve otherwise complex electrostatic problems. These problems involve finding electrostatic potential and electric field on the axis of a uniformly charged ring. Modest programing skills are required of students. (DH)

An electrostatic Particle-In-Cell code on multi-block structured meshes

NASA Astrophysics Data System (ADS)

Meierbachtol, Collin S.; Svyatskiy, Daniil; Delzanno, Gian Luca; Vernon, Louis J.; Moulton, J. David

2017-12-01

We present an electrostatic Particle-In-Cell (PIC) code on multi-block, locally structured, curvilinear meshes called Curvilinear PIC (CPIC). Multi-block meshes are essential to capture complex geometries accurately and with good mesh quality, something that would not be possible with single-block structured meshes that are often used in PIC and for which CPIC was initially developed. Despite the structured nature of the individual blocks, multi-block meshes resemble unstructured meshes in a global sense and introduce several new challenges, such as the presence of discontinuities in the mesh properties and coordinate orientation changes across adjacent blocks, and polyjunction points where an arbitrary number of blocks meet. In CPIC, these challenges have been met by an approach that features: (1) a curvilinear formulation of the PIC method: each mesh block is mapped from the physical space, where the mesh is curvilinear and arbitrarily distorted, to the logical space, where the mesh is uniform and Cartesian on the unit cube; (2) a mimetic discretization of Poisson's equation suitable for multi-block meshes; and (3) a hybrid (logical-space position/physical-space velocity), asynchronous particle mover that mitigates the performance degradation created by the necessity to track particles as they move across blocks. The numerical accuracy of CPIC was verified using two standard plasma-material interaction tests, which demonstrate good agreement with the corresponding analytic solutions. Compared to PIC codes on unstructured meshes, which have also been used for their flexibility in handling complex geometries but whose performance suffers from issues associated with data locality and indirect data access patterns, PIC codes on multi-block structured meshes may offer the best compromise for capturing complex geometries while also maintaining solution accuracy and computational efficiency.

An electrostatic Particle-In-Cell code on multi-block structured meshes

DOE PAGES

Meierbachtol, Collin S.; Svyatskiy, Daniil; Delzanno, Gian Luca; ...

2017-09-14

We present an electrostatic Particle-In-Cell (PIC) code on multi-block, locally structured, curvilinear meshes called Curvilinear PIC (CPIC). Multi-block meshes are essential to capture complex geometries accurately and with good mesh quality, something that would not be possible with single-block structured meshes that are often used in PIC and for which CPIC was initially developed. In spite of the structured nature of the individual blocks, multi-block meshes resemble unstructured meshes in a global sense and introduce several new challenges, such as the presence of discontinuities in the mesh properties and coordinate orientation changes across adjacent blocks, and polyjunction points where anmore » arbitrary number of blocks meet. In CPIC, these challenges have been met by an approach that features: (1) a curvilinear formulation of the PIC method: each mesh block is mapped from the physical space, where the mesh is curvilinear and arbitrarily distorted, to the logical space, where the mesh is uniform and Cartesian on the unit cube; (2) a mimetic discretization of Poisson's equation suitable for multi-block meshes; and (3) a hybrid (logical-space position/physical-space velocity), asynchronous particle mover that mitigates the performance degradation created by the necessity to track particles as they move across blocks. The numerical accuracy of CPIC was verified using two standard plasma–material interaction tests, which demonstrate good agreement with the corresponding analytic solutions. And compared to PIC codes on unstructured meshes, which have also been used for their flexibility in handling complex geometries but whose performance suffers from issues associated with data locality and indirect data access patterns, PIC codes on multi-block structured meshes may offer the best compromise for capturing complex geometries while also maintaining solution accuracy and computational efficiency.« less

An electrostatic Particle-In-Cell code on multi-block structured meshes

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

Meierbachtol, Collin S.; Svyatskiy, Daniil; Delzanno, Gian Luca

We present an electrostatic Particle-In-Cell (PIC) code on multi-block, locally structured, curvilinear meshes called Curvilinear PIC (CPIC). Multi-block meshes are essential to capture complex geometries accurately and with good mesh quality, something that would not be possible with single-block structured meshes that are often used in PIC and for which CPIC was initially developed. In spite of the structured nature of the individual blocks, multi-block meshes resemble unstructured meshes in a global sense and introduce several new challenges, such as the presence of discontinuities in the mesh properties and coordinate orientation changes across adjacent blocks, and polyjunction points where anmore » arbitrary number of blocks meet. In CPIC, these challenges have been met by an approach that features: (1) a curvilinear formulation of the PIC method: each mesh block is mapped from the physical space, where the mesh is curvilinear and arbitrarily distorted, to the logical space, where the mesh is uniform and Cartesian on the unit cube; (2) a mimetic discretization of Poisson's equation suitable for multi-block meshes; and (3) a hybrid (logical-space position/physical-space velocity), asynchronous particle mover that mitigates the performance degradation created by the necessity to track particles as they move across blocks. The numerical accuracy of CPIC was verified using two standard plasma–material interaction tests, which demonstrate good agreement with the corresponding analytic solutions. And compared to PIC codes on unstructured meshes, which have also been used for their flexibility in handling complex geometries but whose performance suffers from issues associated with data locality and indirect data access patterns, PIC codes on multi-block structured meshes may offer the best compromise for capturing complex geometries while also maintaining solution accuracy and computational efficiency.« less

On the role of electrostatics in protein-protein interactions

NASA Astrophysics Data System (ADS)

Zhang, Zhe; Witham, Shawn; Alexov, Emil

2011-06-01

The role of electrostatics in protein-protein interactions and binding is reviewed in this paper. A brief outline of the computational modeling, in the framework of continuum electrostatics, is presented and the basic electrostatic effects occurring upon the formation of the complex are discussed. The effect of the salt concentration and pH of the water phase on protein-protein binding free energy is demonstrated which indicates that the increase of the salt concentration tends to weaken the binding, an observation that is attributed to the optimization of the charge-charge interactions across the interface. It is pointed out that the pH-optimum (pH of optimal binding affinity) varies among the protein-protein complexes, and perhaps is a result of their adaptation to particular subcellular compartments. The similarities and differences between hetero- and homo-complexes are outlined and discussed with respect to the binding mode and charge complementarity.

On the role of electrostatics on protein-protein interactions

PubMed Central

Zhang, Zhe; Witham, Shawn; Alexov, Emil

2011-01-01

The role of electrostatics on protein-protein interactions and binding is reviewed in this article. A brief outline of the computational modeling, in the framework of continuum electrostatics, is presented and basic electrostatic effects occurring upon the formation of the complex are discussed. The role of the salt concentration and pH of the water phase on protein-protein binding free energy is demonstrated and indicates that the increase of the salt concentration tends to weaken the binding, an observation that is attributed to the optimization of the charge-charge interactions across the interface. It is pointed out that the pH-optimum (pH of optimal binding affinity) varies among the protein-protein complexes, and perhaps is a result of their adaptation to particular subcellular compartment. At the end, the similarities and differences between hetero- and homo-complexes are outlined and discussed with respect to the binding mode and charge complementarity. PMID:21572182

A quantum mechanical analysis of the light-harvesting complex 2 (LH2) from purple photosynthetic bacteria: insights into the electrostatic effects of transmembrane helices.

PubMed

Pichierri, Fabio

2011-02-01

We perform a quantum mechanical study of the peptides that are part of the LH2 complex from Rhodopseudomonas acidophila, a non-sulfur purple bacteria that has the ability of producing chemical energy from photosynthesis. The electronic structure calculations indicate that the transmembrane helices of these peptides are characterized by dipole moments with a magnitude of about 150D. When the full nonamer assembly made of 18 peptides is considered, then a macrodipole of magnitude 806D is built up from the vector sum of each monomer dipole. The macrodipole is oriented normal to the membrane plane and with the positive tip toward the cytoplasm thereby indicating that the electronic charge of the protein scaffold is polarized toward the periplasm. The results obtained here suggest that the asymmetric charge distribution of the protein scaffold contributes an anisotropic electrostatic environment which differentiates the absorption properties of the bacteriochlorophyll pigments, B800 and B850, embedded in the LH2 complex. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Electrostatic and structural similarity of classical and non-classical lactam compounds

NASA Astrophysics Data System (ADS)

Coll, Miguel; Frau, Juan; Vilanova, Bartolomé; Donoso, Josefa; Muñoz, Francisco

2001-09-01

Various electrostatic and structural parameters for a series of classical and non-classical β-lactams were determined and compared in order to ascertain whether some specific β-lactams possess antibacterial or β-lactamase inhibitory properties. The electrostatic parameters obtained, based on the Distributed Multipole Analysis (DMA) of high-quality wavefunctions for the studied structures, suggest that some non-classical β-lactams effectively inhibit the action of β-lactamases. As shown in this work, such electrostatic parameters provide much more reliable information about the antibacterial and inhibitory properties of β-lactams than do structural parameters.

Electrostatic contribution to the binding stability of protein-protein complexes.

PubMed

Dong, Feng; Zhou, Huan-Xiang

2006-10-01

To investigate roles of electrostatic interactions in protein binding stability, electrostatic calculations were carried out on a set of 64 mutations over six protein-protein complexes. These mutations alter polar interactions across the interface and were selected for putative dominance of electrostatic contributions to the binding stability. Three protocols of implementing the Poisson-Boltzmann model were tested. In vdW4 the dielectric boundary between the protein low dielectric and the solvent high dielectric is defined as the protein van der Waals surface and the protein dielectric constant is set to 4. In SE4 and SE20, the dielectric boundary is defined as the surface of the protein interior inaccessible to a 1.4-A solvent probe, and the protein dielectric constant is set to 4 and 20, respectively. In line with earlier studies on the barnase-barstar complex, the vdW4 results on the large set of mutations showed the closest agreement with experimental data. The agreement between vdW4 and experiment supports the contention of dominant electrostatic contributions for the mutations, but their differences also suggest van der Waals and hydrophobic contributions. The results presented here will serve as a guide for future refinement in electrostatic calculation and inclusion of nonelectrostatic effects. Proteins 2006. (c) 2006 Wiley-Liss, Inc.

Spacecraft Electrostatic Radiation Shielding

NASA Technical Reports Server (NTRS)

2008-01-01

This project analyzed the feasibility of placing an electrostatic field around a spacecraft to provide a shield against radiation. The concept was originally proposed in the 1960s and tested on a spacecraft by the Soviet Union in the 1970s. Such tests and analyses showed that this concept is not only feasible but operational. The problem though is that most of this work was aimed at protection from 10- to 100-MeV radiation. We now appreciate that the real problem is 1- to 2-GeV radiation. So, the question is one of scaling, in both energy and size. Can electrostatic shielding be made to work at these high energy levels and can it protect an entire vehicle? After significant analysis and consideration, an electrostatic shield configuration was proposed. The selected architecture was a torus, charged to a high negative voltage, surrounding the vehicle, and a set of positively charged spheres. Van de Graaff generators were proposed as the mechanism to move charge from the vehicle to the torus to generate the fields necessary to protect the spacecraft. This design minimized complexity, residual charge, and structural forces and resolved several concerns raised during the internal critical review. But, it still is not clear if such a system is costeffective or feasible, even though several studies have indicated usefulness for radiation protection at energies lower than that of the galactic cosmic rays. Constructing such a system will require power supplies that can generate voltages 10 times that of the state of the art. Of more concern is the difficulty of maintaining the proper net charge on the entire structure and ensuring that its interaction with solar wind will not cause rapid discharge. Yet, if these concerns can be resolved, such a scheme may provide significant radiation shielding to future vehicles, without the excessive weight or complexity of other active shielding techniques.

CPdock: the complementarity plot for docking of proteins: implementing multi-dielectric continuum electrostatics.

PubMed

Basu, Sankar

2017-12-07

The complementarity plot (CP) is an established validation tool for protein structures, applicable to both globular proteins (folding) as well as protein-protein complexes (binding). It computes the shape and electrostatic complementarities (S m , E m ) for amino acid side-chains buried within the protein interior or interface and plots them in a two-dimensional plot having knowledge-based probabilistic quality estimates for the residues as well as for the whole structure. The current report essentially presents an upgraded version of the plot with the implementation of the advanced multi-dielectric functionality (as in Delphi version 6.2 or higher) in the computation of electrostatic complementarity to make the validation tool physico-chemically more realistic. The two methods (single- and multi-dielectric) agree decently in their resultant E m values, and hence, provisions for both methods have been kept in the software suite. So to speak, the global electrostatic balance within a well-folded protein and/or a well-packed interface seems only marginally perturbed by the choice of different internal dielectric values. However, both from theoretical as well as practical grounds, the more advanced multi-dielectric version of the plot is certainly recommended for potentially producing more reliable results. The report also presents a new methodology and a variant plot, namely CP dock , based on the same principles of complementarity specifically designed to be used in the docking of proteins. The efficacy of the method to discriminate between good and bad docked protein complexes has been tested on a recent state-of-the-art docking benchmark. The results unambiguously indicate that CP dock can indeed be effective in the initial screening phase of a docking scoring pipeline before going into more sophisticated and computationally expensive scoring functions. CP dock has been made available at https://github.com/nemo8130/CPdock . Graphical Abstract An example showing the efficacy of CP dock to be used in the initial screening phase of a protein-protein docking scoring pipeline.

Gels of sodium alginate‒chitosan interpolyelectrolyte complexes

NASA Astrophysics Data System (ADS)

Brovko, O. S.; Palamarchuk, I. A.; Val'chuk, N. A.; Chukhchin, D. G.; Bogolitsyn, K. G.; Boitsova, T. A.

2017-08-01

Aspects of the formation of gels of interpolyelectrolyte complexes (IPECs) based on sodium alginate (NaAlg) and chitosan are studied. The effect the conditions of synthesis and complex composition have on the morphological structure and functional properties of these complexes is examined. It is established that complexation in this system proceeds according to a mechanism of electrostatic interaction between the oppositely charged carboxylic groups of the L-hyaluronic acid pyranose cycles of NaAlg proximal polymer chains and chitosan's amino groups, along with a multitude of hydrogen bonds and dispersion forces. We show that the mechanism of IPEC formation is strongly influenced by the conformational state of a lyophilizing component that is present in the system in excess. The inner surfaces of cryogels based on NaAlg‒chitosan IPECs is found to be strongly influenced by the degree of conversion between the parental polyelectrolytes. The most developed mesoporous structure is obtained when a denser gel forms in the system.

Variable stiffness sandwich panels using electrostatic interlocking core

NASA Astrophysics Data System (ADS)

Heath, Callum J. C.; Bond, Ian P.; Potter, Kevin D.

2016-04-01

Structural topology has a large impact on the flexural stiffness of a beam structure. Reversible attachment between discrete substructures allows for control of shear stress transfer between structural elements, thus stiffness modulation. Electrostatic adhesion has shown promise for providing a reversible latching mechanism for controllable internal connectivity. Building on previous research, a thin film copper polyimide laminate has been used to incorporate high voltage electrodes to Fibre Reinforced Polymer (FRP) sandwich structures. The level of electrostatic holding force across the electrode interface is key to the achievable level of stiffness modulation. The use of non-flat interlocking core structures can allow for a significant increase in electrode contact area for a given core geometry, thus a greater electrostatic holding force. Interlocking core geometries based on cosine waves can be Computer Numerical Control (CNC) machined from Rohacell IGF 110 Foam core. These Interlocking Core structures could allow for enhanced variable stiffness functionality compared to basic planar electrodes. This novel concept could open up potential new applications for electrostatically induced variable stiffness structures.

Physical nature of ethidium and proflavine interactions with nucleic acid bases in the intercalation plane.

PubMed

Langner, Karol M; Kedzierski, Pawel; Sokalski, W Andrzej; Leszczynski, Jerzy

2006-05-18

On the basis of the crystallographic structures of three nucleic acid intercalation complexes involving ethidium and proflavine, we have analyzed the interaction energies between intercalator chromophores and their four nearest bases, using a hybrid variation-perturbation method at the second-order Møller-Plesset theory level (MP2) with a 6-31G(d,p) basis set. A total MP2 interaction energy minimum precisely reproduces the crystallographic position of the ethidium chromophore in the intercalation plane between UA/AU bases. The electrostatic component constitutes the same fraction of the total energy for all three studied structures. The multipole electrostatic interaction energy, calculated from cumulative atomic multipole moments (CAMMs), was found to converge only after including components above the fifth order. CAMM interaction surfaces, calculated on grids in the intercalation planes of these structures, reasonably reproduce the alignment of intercalators in crystal structures; they exhibit additional minima in the direction of the DNA grooves, however, which also need to be examined at higher theory levels if no crystallographic data are given.

Hydrogen bonding and pi-stacking: how reliable are force fields? A critical evaluation of force field descriptions of nonbonded interactions.

PubMed

Paton, Robert S; Goodman, Jonathan M

2009-04-01

We have evaluated the performance of a set of widely used force fields by calculating the geometries and stabilization energies for a large collection of intermolecular complexes. These complexes are representative of a range of chemical and biological systems for which hydrogen bonding, electrostatic, and van der Waals interactions play important roles. Benchmark energies are taken from the high-level ab initio values in the JSCH-2005 and S22 data sets. All of the force fields underestimate stabilization resulting from hydrogen bonding, but the energetics of electrostatic and van der Waals interactions are described more accurately. OPLSAA gave a mean unsigned error of 2 kcal mol(-1) for all 165 complexes studied, and outperforms DFT calculations employing very large basis sets for the S22 complexes. The magnitude of hydrogen bonding interactions are severely underestimated by all of the force fields tested, which contributes significantly to the overall mean error; if complexes which are predominantly bound by hydrogen bonding interactions are discounted, the mean unsigned error of OPLSAA is reduced to 1 kcal mol(-1). For added clarity, web-based interactive displays of the results have been developed which allow comparisons of force field and ab initio geometries to be performed and the structures viewed and rotated in three dimensions.

Electrostatics in pharmaceutical aerosols for inhalation.

PubMed

Wong, Jennifer; Chan, Hak-Kim; Kwok, Philip Chi Lip

2013-08-01

Electrostatics continues to play an important role in pharmaceutical aerosols for inhalation. Despite its ubiquitous nature, the charging process is complex and not well understood. Nonetheless, significant advances in the past few years continue to improve understanding and lead to better control of electrostatics. The purpose of this critical review is to present an overview of the literature, with an emphasis on how electrostatic charge can be useful in improving pulmonary drug delivery.

Design evaluation of graphene nanoribbon nanoelectromechanical devices

NASA Astrophysics Data System (ADS)

Lam, Kai-Tak; Stephen Leo, Marie; Lee, Chengkuo; Liang, Gengchiau

2011-07-01

Computational studies on nanoelectromechanical switches based on bilayer graphene nanoribbons (BGNRs) with different designs are presented in this work. By varying the interlayer distance via electrostatic means, the conductance of the BGNR can be changed in order to achieve ON-states and OFF-states, thereby mimicking the function of a switch. Two actuator designs based on the modified capacitive parallel plate (CPP) model and the electrostatic repulsive force (ERF) model are discussed for different applications. Although the CPP design provides a simple electrostatic approach to changing the interlayer distance of the BGNR, their switching gate bias VTH strongly depends on the gate area, which poses a limitation on the size of the device. In addition, there exists a risk of device failure due to static fraction between the mobile and fixed electrodes. In contrast, the ERF design can circumvent both issues with a more complex structure. Finally, optimizations of the devices are carried out in order to provide insights into the design considerations of these nanoelectromechanical switches.

Electrostatic similarity of proteins: Application of three dimensional spherical harmonic decomposition

PubMed Central

Długosz, Maciej; Trylska, Joanna

2008-01-01

We present a method for describing and comparing global electrostatic properties of biomolecules based on the spherical harmonic decomposition of electrostatic potential data. Unlike other approaches our method does not require any prior three dimensional structural alignment. The electrostatic potential, given as a volumetric data set from a numerical solution of the Poisson or Poisson–Boltzmann equation, is represented with descriptors that are rotation invariant. The method can be applied to large and structurally diverse sets of biomolecules enabling to cluster them according to their electrostatic features. PMID:18624502

Electrostatic Forces as Dominant Interactions Between Proteins and Polyanions: an ESI MS Study of Fibroblast Growth Factor Binding to Heparin Oligomers

NASA Astrophysics Data System (ADS)

Minsky, Burcu Baykal; Dubin, Paul L.; Kaltashov, Igor A.

2017-04-01

The interactions between fibroblast growth factors (FGFs) and their receptors (FGFRs) are facilitated by heparan sulfate (HS) and heparin (Hp), highly sulfated biological polyelectrolytes. The molecular basis of FGF interactions with these polyelectrolytes is highly complex due to the structural heterogeneity of HS/Hp, and many details still remain elusive, especially the significance of charge density and minimal chain length of HS/Hp in growth factor recognition and multimerization. In this work, we use electrospray ionization mass spectrometry (ESI MS) to investigate the association of relatively homogeneous oligoheparins (octamer, dp8, and decamer, dp10) with acidic fibroblast growth factor (FGF-1). This growth factor forms 1:1, 2:1, and 3:1 protein/heparinoid complexes with both dp8 and dp10, and the fraction of bound protein is highly dependent on protein/heparinoid molar ratio. Multimeric complexes are preferentially formed on the highly sulfated Hp oligomers. Although a variety of oligomers appear to be binding-competent, there is a strong correlation between the affinity and the overall level of sulfation (the highest charge density polyanions binding FGF most strongly via multivalent interactions). These results show that the interactions between FGF-1 and Hp oligomers are primarily directed by electrostatics, and also demonstrate the power of ESI MS as a tool to study multiple binding equilibria between proteins and structurally heterogeneous polyanions.

A computational study of anion-modulated cation-π interactions.

PubMed

Carrazana-García, Jorge A; Rodríguez-Otero, Jesús; Cabaleiro-Lago, Enrique M

2012-05-24

The interaction of anions with cation-π complexes formed by the guanidinium cation and benzene was thoroughly studied by means of computational methods. Potential energy surface scans were performed in order to evaluate the effect of the anion coming closer to the cation-π pair. Several structures of guanidinium-benzene complexes and anion approaching directions were examined. Supermolecule calculations were performed on ternary complexes formed by guanidinium, benzene, and one anion and the interaction energy was decomposed into its different two- and three-body contributions. The interaction energies were further dissected into their electrostatic, exchange, repulsion, polarization and dispersion contributions by means of local molecular orbital energy decomposition analysis. The results confirm that, besides the electrostatic cation-anion attraction, the effect of the anion over the cation-π interaction is mainly due to polarization and can be rationalized following the changes in the anion-π and the nonadditive (three-body) terms of the interaction. When the cation and the anion are on the same side of the π system, the three-body interaction is anticooperative, but when the anion and the cation are on opposite sides of the π system, the three-body interaction is cooperative. As far as we know, this is the first study where this kind of analysis is carried out with a structured cation as guanidinium with a significant biological interest.

Aqueous Molecular Dynamics Simulations of the M. tuberculosis Enoyl-ACP Reductase-NADH System and Its Complex with a Substrate Mimic or Diphenyl Ethers Inhibitors

PubMed Central

da Silva Lima, Camilo Henrique; de Alencastro, Ricardo Bicca; Kaiser, Carlos Roland; de Souza, Marcus Vinícius Nora; Rodrigues, Carlos Rangel; Albuquerque, Magaly Girão

2015-01-01

Molecular dynamics (MD) simulations of 12 aqueous systems of the NADH-dependent enoyl-ACP reductase from Mycobacterium tuberculosis (InhA) were carried out for up to 20–40 ns using the GROMACS 4.5 package. Simulations of the holoenzyme, holoenzyme-substrate, and 10 holoenzyme-inhibitor complexes were conducted in order to gain more insight about the secondary structure motifs of the InhA substrate-binding pocket. We monitored the lifetime of the main intermolecular interactions: hydrogen bonds and hydrophobic contacts. Our MD simulations demonstrate the importance of evaluating the conformational changes that occur close to the active site of the enzyme-cofactor complex before and after binding of the ligand and the influence of the water molecules. Moreover, the protein-inhibitor total steric (ELJ) and electrostatic (EC) interaction energies, related to Gly96 and Tyr158, are able to explain 80% of the biological response variance according to the best linear equation, pKi = 7.772 − 0.1885 × Gly96 + 0.0517 × Tyr158 (R2 = 0.80; n = 10), where interactions with Gly96, mainly electrostatic, increase the biological response, while those with Tyr158 decrease. These results will help to understand the structure-activity relationships and to design new and more potent anti-TB drugs. PMID:26457706

Computational analysis of aspartic protease plasmepsin II complexed with EH58 inhibitor: a QM/MM MD study.

PubMed

de Farias Silva, Natália; Lameira, Jerônimo; Alves, Cláudio Nahum

2011-10-01

Plasmepsin (PM) II is one of four enzymes in the food vacuole of Plasmodium falciparum. It has become an attractive target for combating malaria through research regarding its importance in the P. falciparum metabolism and life cycle, making it the target of choice for structure-based drug design. This paper reports the results of hybrid quantum mechanics / molecular mechanics (QM/MM) molecular dynamics (MD) simulations employed to study the details of the interactions established between PM II and N-(3-{(2-benzo[1, 3]dioxol-5-yl-ethyl)[3-(1-methyl-3-oxo-1,3-dihydro-isoindol-2-yl) propionyl]-amino}-1-benzyl-2-(hydroxyl-propyl)-4-benzyloxy-3,5dimethoxy-benzamide (EH58), a well-known potent inhibitor for this enzyme. Electrostatic binding free energy and energy terms decomposition have been computed for PM II complexed with the EH58 inhibitor. The results reveal that there is a strong interaction between Asp34, Val78, Ser79, Tyr192 and Asp214 residues and the EH58 inhibitor. In addition, we have computed the potential of the mean force (PMF) profile in order to assign the protonation state of the two catalytic aspartates in PM II-EH58 complex. The results indicate that the protonation of Asp214 favors a stable active site structure, which is consistent with our electrostatic binding free energy calculation and with previous published works.

High-resolution neutron and X-ray diffraction room-temperature studies of an H-FABP-oleic acid complex: study of the internal water cluster and ligand binding by a transferred multipolar electron-density distribution.

PubMed

Howard, E I; Guillot, B; Blakeley, M P; Haertlein, M; Moulin, M; Mitschler, A; Cousido-Siah, A; Fadel, F; Valsecchi, W M; Tomizaki, Takashi; Petrova, T; Claudot, J; Podjarny, A

2016-03-01

Crystal diffraction data of heart fatty acid binding protein (H-FABP) in complex with oleic acid were measured at room temperature with high-resolution X-ray and neutron protein crystallography (0.98 and 1.90 Å resolution, respectively). These data provided very detailed information about the cluster of water molecules and the bound oleic acid in the H-FABP large internal cavity. The jointly refined X-ray/neutron structure of H-FABP was complemented by a transferred multipolar electron-density distribution using the parameters of the ELMAMII library. The resulting electron density allowed a precise determination of the electrostatic potential in the fatty acid (FA) binding pocket. Bader's quantum theory of atoms in molecules was then used to study interactions involving the internal water molecules, the FA and the protein. This approach showed H⋯H contacts of the FA with highly conserved hydrophobic residues known to play a role in the stabilization of long-chain FAs in the binding cavity. The determination of water hydrogen (deuterium) positions allowed the analysis of the orientation and electrostatic properties of the water molecules in the very ordered cluster. As a result, a significant alignment of the permanent dipoles of the water molecules with the protein electrostatic field was observed. This can be related to the dielectric properties of hydration layers around proteins, where the shielding of electrostatic interactions depends directly on the rotational degrees of freedom of the water molecules in the interface.

pyDockWEB: a web server for rigid-body protein-protein docking using electrostatics and desolvation scoring.

PubMed

Jiménez-García, Brian; Pons, Carles; Fernández-Recio, Juan

2013-07-01

pyDockWEB is a web server for the rigid-body docking prediction of protein-protein complex structures using a new version of the pyDock scoring algorithm. We use here a new custom parallel FTDock implementation, with adjusted grid size for optimal FFT calculations, and a new version of pyDock, which dramatically speeds up calculations while keeping the same predictive accuracy. Given the 3D coordinates of two interacting proteins, pyDockWEB returns the best docking orientations as scored mainly by electrostatics and desolvation energy. The server does not require registration by the user and is freely accessible for academics at http://life.bsc.es/servlet/pydock. Supplementary data are available at Bioinformatics online.

Electrostatic effects in the collapse transition of phospholiquid monolayer

NASA Astrophysics Data System (ADS)

Nguyen, Toan T.; Gopal, Ajaykumar; Lee, Ka Yee C.; Witten, Thomas A.

2004-03-01

We study the collapse transition of fluidic phospholipid surfactant monolayers under lateral compression. DMPC, DPPC or POPG surfactants and their binary mixtures are used. Various collapsed structures (circular discs, cylinderical tubes and pearls-on-a-string) were observed during the transition. We show that electrostatics plays an important role in the formation of these structures. By changing the composition of charged surfactant (POGP) or the screening condition of the solution, one can change the dominant collapsed structure from discs to tubes to pearls in the order of increasing the strength of electrostatic interactions, in accordance with theoretical estimates. We also study a complimentary electrostatic effect due charge relaxation in the transitions between these structures. It is shown that free energy gained from relaxations of charge molecule is small and can be neglected when considering electrostatics of these systems.

Electrostatic modification of novel materials

NASA Astrophysics Data System (ADS)

Ahn, C. H.; Bhattacharya, A.; di Ventra, M.; Eckstein, J. N.; Frisbie, C. Daniel; Gershenson, M. E.; Goldman, A. M.; Inoue, I. H.; Mannhart, J.; Millis, Andrew J.; Morpurgo, Alberto F.; Natelson, Douglas; Triscone, Jean-Marc

2006-10-01

Application of the field-effect transistor principle to novel materials to achieve electrostatic doping is a relatively new research area. It may provide the opportunity to bring about modifications of the electronic and magnetic properties of materials through controlled and reversible changes of the carrier concentration without modifying the level of disorder, as occurs when chemical composition is altered. As well as providing a basis for new devices, electrostatic doping can in principle serve as a tool for studying quantum critical behavior, by permitting the ground state of a system to be tuned in a controlled fashion. In this paper progress in electrostatic doping of a number of materials systems is reviewed. These include structures containing complex oxides, such as cuprate superconductors and colossal magnetoresistive compounds, organic semiconductors, in the form of both single crystals and thin films, inorganic layered compounds, single molecules, and magnetic semiconductors. Recent progress in the field is discussed, including enabling experiments and technologies, open scientific issues and challenges, and future research opportunities. For many of the materials considered, some of the results can be anticipated by combining knowledge of macroscopic or bulk properties and the understanding of the field-effect configuration developed during the course of the evolution of conventional microelectronics. However, because electrostatic doping is an interfacial phenomenon, which is largely an unexplored field, real progress will depend on the development of a better understanding of lattice distortion and charge transfer at interfaces in these systems.

Free energy landscapes of encounter complexes in protein-protein association.

PubMed

Camacho, C J; Weng, Z; Vajda, S; DeLisi, C

1999-03-01

We report the computer generation of a high-density map of the thermodynamic properties of the diffusion-accessible encounter conformations of four receptor-ligand protein pairs, and use it to study the electrostatic and desolvation components of the free energy of association. Encounter complex conformations are generated by sampling the translational/rotational space of the ligand around the receptor, both at 5-A and zero surface-to-surface separations. We find that partial desolvation is always an important effect, and it becomes dominant for complexes in which one of the reactants is neutral or weakly charged. The interaction provides a slowly varying attractive force over a small but significant region of the molecular surface. In complexes with no strong charge complementarity this region surrounds the binding site, and the orientation of the ligand in the encounter conformation with the lowest desolvation free energy is similar to the one observed in the fully formed complex. Complexes with strong opposite charges exhibit two types of behavior. In the first group, represented by barnase/barstar, electrostatics exerts strong orientational steering toward the binding site, and desolvation provides some added adhesion within the local region of low electrostatic energy. In the second group, represented by the complex of kallikrein and pancreatic trypsin inhibitor, the overall stability results from the rather nonspecific electrostatic attraction, whereas the affinity toward the binding region is determined by desolvation interactions.

Structure of 1:1 complex of 1-naphthylmethyl ester of monensin A with sodium perchlorate studied by X-ray, FT-IR and ab initio methods

NASA Astrophysics Data System (ADS)

Huczyński, Adam; Janczak, Jan; Brzezinski, Bogumil

2012-12-01

A new crystalline complex formed between 1-naphthylmethyl ester of the naturally occurring antibiotic - monensin A (MON8) with sodium perchlorate has been obtained and studied using X-ray crystallography and FT-IR spectroscopy. The X-ray data of the complex show that MON8 forms a pseudo-cyclic structure stabilised by one weak intramolecular hydrogen bond and the sodium cation co-ordinated by two oxygen atoms of hydroxyl groups and four etheric oxygen atoms in the hydrophilic sphere. Within this structure the oxygen atoms of the ester groups are not involved in the coordination of sodium cation. In contrast to the solid state structure of the complex, in acetonitrile solution an equilibrium between two structures, in which the oxygen atom of the carbonyl ester group is either involved or not involved in the complexation of the sodium cation, is found. In acetonitrile this equilibrium is shifted towards the latter structure i.e. the structure existing in the solid state. The gas-phase structure of [MON8sbnd Na]+ cation as shown the ab initio MO calculations is comparable with the crystal one. Three-dimensional molecular electrostatic potential calculated for the neutral MON8 and [MON8sbnd Na]+ molecules is helpful for understanding the structural aspects of the sodium complex formation.

Experimental study of electrostatic discharges of spacecraft solar array protective coatings under radiation

NASA Astrophysics Data System (ADS)

Khasanshin, Rashid; Novikov, Lev

Action of charged particles on low-conductive dielectrics causes formation of areas with a high charge density inside; their fields may give rise to development of electrostatic discharge between the charged area and the surface of the dielectric. Discharge channels are growing due to breakdown of dielectric and formation of a conducting phase. Generation of the channels is a complex stochastic process accompanied by such physical and chemical processes as ionization, gas formation, heating, and so on, which cause formation of conducting phase in a glass. That is why no quantitative theory describing formation of conductive channels has been formulated yet. The study of electrostatic discharges in dielectrics under radiation is essential both from a scientific point of view and for the solution of applied problems. In particular, interaction of a spacecraft with ambient plasma causes accumulation of electric charges on its surface producing, as a consequence, electric potential between the spacecraft surface and the plasma. For example, potentials on the surface of satellites operating on a geostationary orbit reach up to 20 kV. Elec-trostatic discharges caused by such potentials can produce not only the considerable electromag-netic interference, but also lead to the destruction of hardware components and structural ele-ments. Electrostatic charging due to electrons from the Earth’s radiation belts causes degradation of solar arrays as a result of surface and internal electrostatic discharges. In the work, surface of K-208 spacecraft solar array protective coatings irradiated by 20 and 40 keV electrons and protons has studied using by AFM methods. Traces of electrostatic dis-charges at different radiation flux densities were analyzed.

Compact electrostatic comb actuator

DOEpatents

Rodgers, M. Steven; Burg, Michael S.; Jensen, Brian D.; Miller, Samuel L.; Barnes, Stephen M.

2000-01-01

A compact electrostatic comb actuator is disclosed for microelectromechanical (MEM) applications. The actuator is based upon a plurality of meshed electrostatic combs, some of which are stationary and others of which are moveable. One or more restoring springs are fabricated within an outline of the electrostatic combs (i.e. superposed with the moveable electrostatic combs) to considerably reduce the space required for the actuator. Additionally, a truss structure is provided to support the moveable electrostatic combs and prevent bending or distortion of these combs due to unbalanced electrostatic forces or external loading. The truss structure formed about the moveable electrostatic combs allows the spacing between the interdigitated fingers of the combs to be reduced to about one micron or less, thereby substantially increasing the number of active fingers which can be provided in a given area. Finally, electrostatic shields can be used in the actuator to substantially reduce unwanted electrostatic fields to further improve performance of the device. As a result, the compact electrostatic comb actuator of the present invention occupies only a fraction of the space required for conventional electrostatic comb actuators, while providing a substantial increase in the available drive force (up to one-hundred times).

Insight into the structure of photosynthetic LH2 aggregate from spectroscopy simulations.

PubMed

Rancova, Olga; Sulskus, Juozas; Abramavicius, Darius

2012-07-12

Using the electrostatic model of intermolecular interactions, we obtain the Frenkel exciton Hamiltonian parameters for the chlorophyll Qy band of a photosynthetic peripheral light harvesting complex LH2 of a purple bacteria Rhodopseudomonas acidophila from structural data. The intermolecular couplings are mostly determined by the chlorophyll relative positions, whereas the molecular transition energies are determined by the background charge distribution of the whole complex. The protonation pattern of titratable residues is used as a tunable parameter. By studying several protonation state scenarios for distinct protein groups and comparing the simulated absorption and circular dichroism spectra to experiment, we determine the most probable configuration of the protonation states of various side groups of the protein.

Defining protein electrostatic recognition processes

NASA Astrophysics Data System (ADS)

Getzoff, Elizabeth D.; Roberts, Victoria A.

The objective is to elucidate the nature of electrostatic forces controlling protein recognition processes by using a tightly coupled computational and interactive computer graphics approach. The TURNIP program was developed to determine the most favorable precollision orientations for two molecules by systematic search of all orientations and evaluation of the resulting electrostatic interactions. TURNIP was applied to the transient interaction between two electron transfer metalloproteins, plastocyanin and cytochrome c. The results suggest that the productive electron-transfer complex involves interaction of the positive region of cytochrome c with the negative patch of plastocyanin, consistent with experimental data. Application of TURNIP to the formation of the stable complex between the HyHEL-5 antibody and its protein antigen lysozyme showed that long-distance electrostatic forces guide lysozyme toward the HyHEL-5 binding site, but do not fine tune its orientation. Determination of docked antigen/antibody complexes requires including steric as well as electrostatic interactions, as was done for the U10 mutant of the anti-phosphorylcholine antibody S107. The graphics program Flex, a convenient desktop workstation program for visualizing molecular dynamics and normal mode motions, was enhanced. Flex now has a user interface and was rewritten to use standard graphics libraries, so as to run on most desktop workstations.

T-Cell Receptors Binding Orientation over Peptide/MHC Class I Is Driven by Long-Range Interactions

PubMed Central

Ferber, Mathias; Zoete, Vincent; Michielin, Olivier

2012-01-01

Crystallographic data about T-Cell Receptor – peptide – major histocompatibility complex class I (TCRpMHC) interaction have revealed extremely diverse TCR binding modes triggering antigen recognition. Understanding the molecular basis that governs TCR orientation over pMHC is still a considerable challenge. We present a simplified rigid approach applied on all non-redundant TCRpMHC crystal structures available. The CHARMM force field in combination with the FACTS implicit solvation model is used to study the role of long-distance interactions between the TCR and pMHC. We demonstrate that the sum of the coulomb interactions and the electrostatic solvation energies is sufficient to identify two orientations corresponding to energetic minima at 0° and 180° from the native orientation. Interestingly, these results are shown to be robust upon small structural variations of the TCR such as changes induced by Molecular Dynamics simulations, suggesting that shape complementarity is not required to obtain a reliable signal. Accurate energy minima are also identified by confronting unbound TCR crystal structures to pMHC. Furthermore, we decompose the electrostatic energy into residue contributions to estimate their role in the overall orientation. Results show that most of the driving force leading to the formation of the complex is defined by CDR1,2/MHC interactions. This long-distance contribution appears to be independent from the binding process itself, since it is reliably identified without considering neither short-range energy terms nor CDR induced fit upon binding. Ultimately, we present an attempt to predict the TCR/pMHC binding mode for a TCR structure obtained by homology modeling. The simplicity of the approach and the absence of any fitted parameters make it also easily applicable to other types of macromolecular protein complexes. PMID:23251658

T-cell receptors binding orientation over peptide/MHC class I is driven by long-range interactions.

PubMed

Ferber, Mathias; Zoete, Vincent; Michielin, Olivier

2012-01-01

Crystallographic data about T-Cell Receptor - peptide - major histocompatibility complex class I (TCRpMHC) interaction have revealed extremely diverse TCR binding modes triggering antigen recognition. Understanding the molecular basis that governs TCR orientation over pMHC is still a considerable challenge. We present a simplified rigid approach applied on all non-redundant TCRpMHC crystal structures available. The CHARMM force field in combination with the FACTS implicit solvation model is used to study the role of long-distance interactions between the TCR and pMHC. We demonstrate that the sum of the coulomb interactions and the electrostatic solvation energies is sufficient to identify two orientations corresponding to energetic minima at 0° and 180° from the native orientation. Interestingly, these results are shown to be robust upon small structural variations of the TCR such as changes induced by Molecular Dynamics simulations, suggesting that shape complementarity is not required to obtain a reliable signal. Accurate energy minima are also identified by confronting unbound TCR crystal structures to pMHC. Furthermore, we decompose the electrostatic energy into residue contributions to estimate their role in the overall orientation. Results show that most of the driving force leading to the formation of the complex is defined by CDR1,2/MHC interactions. This long-distance contribution appears to be independent from the binding process itself, since it is reliably identified without considering neither short-range energy terms nor CDR induced fit upon binding. Ultimately, we present an attempt to predict the TCR/pMHC binding mode for a TCR structure obtained by homology modeling. The simplicity of the approach and the absence of any fitted parameters make it also easily applicable to other types of macromolecular protein complexes.

Molecular Basis for Structural Heterogeneity of an Intrinsically Disordered Protein Bound to a Partner by Combined ESI-IM-MS and Modeling

NASA Astrophysics Data System (ADS)

D'Urzo, Annalisa; Konijnenberg, Albert; Rossetti, Giulia; Habchi, Johnny; Li, Jinyu; Carloni, Paolo; Sobott, Frank; Longhi, Sonia; Grandori, Rita

2015-03-01

Intrinsically disordered proteins (IDPs) form biologically active complexes that can retain a high degree of conformational disorder, escaping structural characterization by conventional approaches. An example is offered by the complex between the intrinsically disordered NTAIL domain and the phosphoprotein X domain (PXD) from measles virus (MeV). Here, distinct conformers of the complex are detected by electrospray ionization-mass spectrometry (ESI-MS) and ion mobility (IM) techniques yielding estimates for the solvent-accessible surface area (SASA) in solution and the average collision cross-section (CCS) in the gas phase. Computational modeling of the complex in solution, based on experimental constraints, provides atomic-resolution structural models featuring different levels of compactness. The resulting models indicate high structural heterogeneity. The intermolecular interactions are predominantly hydrophobic, not only in the ordered core of the complex, but also in the dynamic, disordered regions. Electrostatic interactions become involved in the more compact states. This system represents an illustrative example of a hydrophobic complex that could be directly detected in the gas phase by native mass spectrometry. This work represents the first attempt to modeling the entire NTAIL domain bound to PXD at atomic resolution.

Rheological and structural characterization of agar/whey proteins insoluble complexes.

PubMed

Rocha, Cristina M R; Souza, Hiléia K S; Magalhães, Natália F; Andrade, Cristina T; Gonçalves, Maria Pilar

2014-09-22

Complex coacervation between whey proteins and carboxylated or highly sulphated polysaccharides has been widely studied. The aim of this work was to characterise a slightly sulphated polysaccharide (agar) and whey protein insoluble complexes in terms of yield, composition and physicochemical properties as well as to study their rheological behaviour for better understanding their structure. Unlike other sulphated polysaccharides, complexation of agar and whey protein at pH 3 in the absence of a buffering agent resulted in a coacervate that was a gel at 20°C with rheological properties and structure similar to those of simple agar gels, reinforced by proteins electrostatically aggregated to the agar network. The behaviour towards heat treatment was similar to that of agar alone, with a high thermal hysteresis and almost full reversibility. In the presence of citrate buffer, the result was a "flocculated solid", with low water content (75-81%), whose properties were governed by protein behaviour. Copyright © 2014 Elsevier Ltd. All rights reserved.

Roles of Long-range Electrostatic Domain Interactions and K+ in Phosphoenzyme Transition of Ca2+-ATPase*

PubMed Central

Yamasaki, Kazuo; Daiho, Takashi; Danko, Stefania; Suzuki, Hiroshi

2013-01-01

Sarcoplasmic reticulum Ca2+-ATPase couples the motions and rearrangements of three cytoplasmic domains (A, P, and N) with Ca2+ transport. We explored the role of electrostatic force in the domain dynamics in a rate-limiting phosphoenzyme (EP) transition by a systematic approach combining electrostatic screening with salts, computer analysis of electric fields in crystal structures, and mutations. Low KCl concentration activated and increasing salt above 0.1 m inhibited the EP transition. A plot of the logarithm of the transition rate versus the square of the mean activity coefficient of the protein gave a linear relationship allowing division of the activation energy into an electrostatic component and a non-electrostatic component in which the screenable electrostatic forces are shielded by salt. Results show that the structural change in the transition is sterically restricted, but that strong electrostatic forces, when K+ is specifically bound at the P domain, come into play to accelerate the reaction. Electric field analysis revealed long-range electrostatic interactions between the N and P domains around their hinge. Mutations of the residues directly involved and other charged residues at the hinge disrupted in parallel the electric field and the structural transition. Favorable electrostatics evidently provides a low energy path for the critical N domain motion toward the P domain, overcoming steric restriction. The systematic approach employed here is, in general, a powerful tool for understanding the structural mechanisms of enzymes. PMID:23737524

Mechanics of the Cell

NASA Astrophysics Data System (ADS)

Boal, David

2012-01-01

Preface; List of symbols; 1. Introduction to the cell; 2. Soft materials and fluids; Part I. Rods and Ropes: 3. Polymers; 4. Complex filaments; 5. Two-dimensional networks; 6. Three-dimensional networks; Part II. Membranes: 7. Biomembranes; 8. Membrane undulations; 9. Intermembrane and electrostatic forces; Part III. The Whole Cell: 10. Structure of the simplest cells; 11. Dynamic filaments; 12. Growth and division; 13. Signals and switches; Appendixes; Glossary; References; Index.

Full-Particle Simulations on Electrostatic Plasma Environment near Lunar Vertical Holes

NASA Astrophysics Data System (ADS)

Miyake, Y.; Nishino, M. N.

2015-12-01

The Kaguya satellite and the Lunar Reconnaissance Orbiter have observed a number of vertical holes on the terrestrial Moon [Haruyama et al., GRL, 2009; Robinson et al., PSS, 2012], which have spatial scales of tens of meters and are possible lava tube skylights. The hole structure has recently received particular attention, because the structure gives an important clue to the complex volcanic history of the Moon. The holes also have high potential as locations for constructing future lunar bases, because of fewer extra-lunar rays/particles and micrometeorites reaching the hole bottoms. In this sense, these holes are not only interesting in selenology, but are also significant from the viewpoint of electrostatic environments. The subject can also be an interesting resource of research in comparative planetary science, because hole structures have been found in other solar system bodies such as the Mars. The lunar dayside electrostatic environment is governed by electrodynamic interactions among the solar wind plasma, photoelectrons, and the charged lunar surface, providing topologically complex boundaries to the plasma. We use the three-dimensional, massively-parallelized, particle-in-cell simulation code EMSES [Miyake and Usui, POP, 2009] to simulate the near-hole plasma environment on the Moon [Miyake and Nishino, Icarus, 2015]. We took into account the solar wind plasma downflow, photoelectron emission from the sunlit part of the lunar surface, and plasma charge deposition on the surface. The simulation domain consists of 400×400×2000 grid points and contains about 25 billion plasma macro-particles. Thus, we need to use supercomputers for the simulations. The vertical wall of the hole introduces a new boundary for both photo and solar wind electrons. The current balance condition established at a hole bottom is altered by the limited solar wind electron penetration into the hole and complex photoelectron current paths inside the hole. The self-consistent modeling not only reproduces intense differential charging between sunlit and shadowed surfaces, but also reveals the potential difference between sunlit surfaces inside and outside the hole. The results demonstrate the uniqueness of the near-hole plasma environment as well as provide useful knowledge for future landing missions.

Role of electrostatic interactions in binding of peptides and intrinsically disordered proteins to their folded targets. 1. NMR and MD characterization of the complex between the c-Crk N-SH3 domain and the peptide Sos.

PubMed

Xue, Yi; Yuwen, Tairan; Zhu, Fangqiang; Skrynnikov, Nikolai R

2014-10-21

Intrinsically disordered proteins (IDPs) often rely on electrostatic interactions to bind their structured targets. To obtain insight into the mechanism of formation of the electrostatic encounter complex, we investigated the binding of the peptide Sos (PPPVPPRRRR), which serves as a minimal model for an IDP, to the c-Crk N-terminal SH3 domain. Initially, we measured ¹⁵N relaxation rates at two magnetic field strengths and determined the binding shifts for the complex of Sos with wild-type SH3. We have also recorded a 3 μs molecular dynamics (MD) trajectory of this complex using the Amber ff99SB*-ILDN force field. The comparison of the experimental and simulated data shows that MD simulation consistently overestimates the strength of salt bridge interactions at the binding interface. The series of simulations using other advanced force fields also failed to produce any satisfactory results. To address this issue, we have devised an empirical correction to the Amber ff99SB*-ILDN force field whereby the Lennard-Jones equilibrium distance for the nitrogen-oxygen pair across the Arg-to-Asp and Arg-to-Glu salt bridges has been increased by 3%. Implementing this correction resulted in a good agreement between the simulations and the experiment. Adjusting the strength of salt bridge interactions removed a certain amount of strain contained in the original MD model, thus improving the binding of the hydrophobic N-terminal portion of the peptide. The arginine-rich C-terminal portion of the peptide, freed from the effect of the overstabilized salt bridges, was found to interconvert more rapidly between its multiple conformational states. The modified MD protocol has also been successfully used to simulate the entire binding process. In doing so, the peptide was initially placed high above the protein surface. It then arrived at the correct bound pose within ∼2 Å of the crystallographic coordinates. This simulation allowed us to analyze the details of the dynamic binding intermediate, i.e., the electrostatic encounter complex. However, an experimental characterization of this transient, weakly populated state remains out of reach. To overcome this problem, we designed the double mutant of c-Crk N-SH3 in which mutations Y186L and W169F abrogate tight Sos binding and shift the equilibrium toward the intermediate state resembling the electrostatic encounter complex. The results of the combined NMR and MD study of this engineered system will be reported in the next part of this paper.

Structure and Electronic Spectra of Purine-Methyl Viologen Charge Transfer Complexes

PubMed Central

Jalilov, Almaz S.; Patwardhan, Sameer; Singh, Arunoday; Simeon, Tomekia; Sarjeant, Amy A.; Schatz, George C.; Lewis, Frederick D.

2014-01-01

The structure and properties of the electron donor-acceptor complexes formed between methyl viologen (MV) and purine nucleosides and nucleotides in water and the solid state have been investigated using a combination of experimental and theoretical methods. Solution studies were performed using UV-vis and 1H NMR spectroscopy. Theoretical calculations were performed within the framework of density functional theory (DFT). Energy decomposition analysis indicates that dispersion and induction (charge-transfer) interactions dominate the total binding energy, whereas electrostatic interactions are largely repulsive. The appearance of charge transfer bands in the absorption spectra of the complexes are well described by time-dependent (TD) DFT and are further explained in terms of the redox properties of purine monomers and solvation effects. Crystal structures are reported for complexes of methyl viologen with the purines 2′-deoxyguanosine 3′-monophosphate GMP (DAD′DAD′ type) and 7-deazaguanosine zG (DAD′ADAD′ type). Comparison of the structures determined in the solid state and by theoretical methods in solution provides valuable insights into the nature of charge-transfer interactions involving purine bases as electron donors. PMID:24294996

Sorption Mechanisms of Antibiotic Cephapirin onto Quartz and Feldspar by Raman Spectroscopy

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

Peterson, Jonathan; Wang, Wei; Gu, Baohua

2009-01-01

Raman spectroscopy was used to investigate the sorption mechanisms of cephapirin (CHP), a veterinary antibiotic, onto quartz (SiO2) and feldspar (KAlSi3O8) at different pH values. Depending on the charge and surface properties of the mineral, different reaction mechanisms including electrostatic attraction, monodentate and bidentate complexation were found to be responsible for CHP sorption. The zwitterion (CHPo) adsorbs to a quartz(+) surface by electrostatic attraction of the carboxylate anion group ( COO-) at a low pH, but adsorbs to a quartz(-) surface through electrostatic attraction of the pyridinium cation and possibly COO- bridge complexes at relatively higher pH conditions. CHP- bondsmore » to a quartz(-) surface by bidentate complexation between one oxygen of COO- and oxygen from the carbonyl (C=O) of the acetoxymethyl group. On a feldspar surface of mixed charge, CHPo forms monodentate complexes between C=O as well as COO- bridging complexes or electrostatically attached to localized edge (hydr)oxy-Al surfaces. CHP- adsorbs to feldspar(-) through monodentate C=O complexation, and similar mechanisms may operate for the sorption of other cephalosporins. This research demonstrates, for the first time, that Raman spectroscopic techniques can be effective for evaluating the sorption processes and mechanisms of cephalosporin antibiotics even at relatively low sorbed concentrations (97-120 μmol/kg).« less

MM-ISMSA: An Ultrafast and Accurate Scoring Function for Protein-Protein Docking.

PubMed

Klett, Javier; Núñez-Salgado, Alfonso; Dos Santos, Helena G; Cortés-Cabrera, Álvaro; Perona, Almudena; Gil-Redondo, Rubén; Abia, David; Gago, Federico; Morreale, Antonio

2012-09-11

An ultrafast and accurate scoring function for protein-protein docking is presented. It includes (1) a molecular mechanics (MM) part based on a 12-6 Lennard-Jones potential; (2) an electrostatic component based on an implicit solvent model (ISM) with individual desolvation penalties for each partner in the protein-protein complex plus a hydrogen bonding term; and (3) a surface area (SA) contribution to account for the loss of water contacts upon protein-protein complex formation. The accuracy and performance of the scoring function, termed MM-ISMSA, have been assessed by (1) comparing the total binding energies, the electrostatic term, and its components (charge-charge and individual desolvation energies), as well as the per residue contributions, to results obtained with well-established methods such as APBSA or MM-PB(GB)SA for a set of 1242 decoy protein-protein complexes and (2) testing its ability to recognize the docking solution closest to the experimental structure as that providing the most favorable total binding energy. For this purpose, a test set consisting of 15 protein-protein complexes with known 3D structure mixed with 10 decoys for each complex was used. The correlation between the values afforded by MM-ISMSA and those from the other methods is quite remarkable (r(2) ∼ 0.9), and only 0.2-5.0 s (depending on the number of residues) are spent on a single calculation including an all vs all pairwise energy decomposition. On the other hand, MM-ISMSA correctly identifies the best docking solution as that closest to the experimental structure in 80% of the cases. Finally, MM-ISMSA can process molecular dynamics trajectories and reports the results as averaged values with their standard deviations. MM-ISMSA has been implemented as a plugin to the widely used molecular graphics program PyMOL, although it can also be executed in command-line mode. MM-ISMSA is distributed free of charge to nonprofit organizations.

Cation and anion dependence of stable geometries and stabilization energies of alkali metal cation complexes with FSA(-), FTA(-), and TFSA(-) anions: relationship with physicochemical properties of molten salts.

PubMed

Tsuzuki, Seiji; Kubota, Keigo; Matsumoto, Hajime

2013-12-19

Stable geometries and stabilization energies (Eform) of the alkali metal complexes with bis(fluorosulfonyl)amide, (fluorosulfonyl)(trifluoromethylslufonyl)amide and bis(trifluoromethylsulfonyl)amide (FSA(-), FTA(-) and TFSA(-)) were studied by ab initio molecular orbital calculations. The FSA(-) complexes prefer the bidentate structures in which two oxygen atoms of two SO2 groups have contact with the metal cation. The FTA(-) and TFSA(-) complexes with Li(+) and Na(+) prefer the bidentate structures, while the FTA(-) and TFSA(-) complexes with Cs(+) prefer tridentate structures in which the metal cation has contact with two oxygen atoms of an SO2 group and one oxygen atom of another SO2 group. The two structures are nearly isoenergetic in the FTA(-) and TFSA(-) complexes with K(+) and Rb(+). The magnitude of Eform depends on the alkali metal cation significantly. The Eform calculated for the most stable TFSA(-) complexes with Li(+), Na(+), K(+), Rb(+) and Cs(+) cations at the MP2/6-311G** level are -137.2, -110.5, -101.1, -89.6, and -84.1 kcal/mol, respectively. The viscosity and ionic conductivity of the alkali TFSA molten salts have strong correlation with the magnitude of the attraction. The viscosity increases and the ionic conductivity decreases with the increase of the attraction. The melting points of the alkali TFSA and alkali BETA molten salts also have correlation with the magnitude of the Eform, which strongly suggests that the magnitude of the attraction play important roles in determining the melting points of these molten salts. The anion dependence of the Eform calculated for the complexes is small (less than 2.9 kcal/mol). This shows that the magnitude of the attraction is not the cause of the low melting points of alkali FTA molten salts compared with those of corresponding alkali TFSA molten salts. The electrostatic interactions are the major source of the attraction in the complexes. The electrostatic energies for the most stable TFSA(-) complexes with the five alkali metal cations are -140.3, -119.4, -104.1, -96.9, and -91.1 kcal/mol, respectively. The induction interactions also contribute to the attraction. In particular, the induction interactions are large in the Li(+) complexes. The induction energies for the five complexes are -46.6, -25.2, -17.5, -13.3, and -10.4 kcal/mol, respectively.

The polarized Debye sheath effect on Kadomtsev-Petviashvili electrostatic structures in strongly coupled dusty plasma

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

Shahmansouri, M.; Alinejad, H.

2015-04-15

We give a theoretical investigation on the dynamics of nonlinear electrostatic waves in a strongly coupled dusty plasma with strong electrostatic interaction between dust grains in the presence of the polarization force (i.e., the force due to the polarized Debye sheath). Adopting a reductive perturbation method, we derived a three-dimensional Kadomtsev-Petviashvili equation that describes the evolution of weakly nonlinear electrostatic localized waves. The energy integral equation is used to study the existence domains of the localized structures. The analysis provides the localized structure existence region, in terms of the effects of strong interaction between the dust particles and polarization force.

Influence of pea protein aggregates on the structure and stability of pea protein/soybean polysaccharide complex emulsions.

PubMed

Yin, Baoru; Zhang, Rujing; Yao, Ping

2015-03-20

The applications of plant proteins in the food and beverage industry have been hampered by their precipitation in acidic solution. In this study, pea protein isolate (PPI) with poor dispersibility in acidic solution was used to form complexes with soybean soluble polysaccharide (SSPS), and the effects of PPI aggregates on the structure and stability of PPI/SSPS complex emulsions were investigated. Under acidic conditions, high pressure homogenization disrupts the PPI aggregates and the electrostatic attraction between PPI and SSPS facilitates the formation of dispersible PPI/SSPS complexes. The PPI/SSPS complex emulsions prepared from the PPI containing aggregates prove to possess similar droplet structure and similar stability compared with the PPI/SSPS emulsions produced from the PPI in which the aggregates have been previously removed by centrifugation. The oil droplets are protected by PPI/SSPS complex interfacial films and SSPS surfaces. The emulsions show long-term stability against pH and NaCl concentration changes. This study demonstrates that PPI aggregates can also be used to produce stable complex emulsions, which may promote the applications of plant proteins in the food and beverage industry.

Reintroducing electrostatics into macromolecular crystallographic refinement: application to neutron crystallography and DNA hydration.

PubMed

Fenn, Timothy D; Schnieders, Michael J; Mustyakimov, Marat; Wu, Chuanjie; Langan, Paul; Pande, Vijay S; Brunger, Axel T

2011-04-13

Most current crystallographic structure refinements augment the diffraction data with a priori information consisting of bond, angle, dihedral, planarity restraints, and atomic repulsion based on the Pauli exclusion principle. Yet, electrostatics and van der Waals attraction are physical forces that provide additional a priori information. Here, we assess the inclusion of electrostatics for the force field used for all-atom (including hydrogen) joint neutron/X-ray refinement. Two DNA and a protein crystal structure were refined against joint neutron/X-ray diffraction data sets using force fields without electrostatics or with electrostatics. Hydrogen-bond orientation/geometry favors the inclusion of electrostatics. Refinement of Z-DNA with electrostatics leads to a hypothesis for the entropic stabilization of Z-DNA that may partly explain the thermodynamics of converting the B form of DNA to its Z form. Thus, inclusion of electrostatics assists joint neutron/X-ray refinements, especially for placing and orienting hydrogen atoms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reintroducing Electrostatics into Macromolecular Crystallographic Refinement: Application to Neutron Crystallography and DNA Hydration

PubMed Central

Fenn, Timothy D.; Schnieders, Michael J.; Mustyakimov, Marat; Wu, Chuanjie; Langan, Paul; Pande, Vijay S.; Brunger, Axel T.

2011-01-01

Summary Most current crystallographic structure refinements augment the diffraction data with a priori information consisting of bond, angle, dihedral, planarity restraints and atomic repulsion based on the Pauli exclusion principle. Yet, electrostatics and van der Waals attraction are physical forces that provide additional a priori information. Here we assess the inclusion of electrostatics for the force field used for all-atom (including hydrogen) joint neutron/X-ray refinement. Two DNA and a protein crystal structure were refined against joint neutron/X-ray diffraction data sets using force fields without electrostatics or with electrostatics. Hydrogen bond orientation/geometry favors the inclusion of electrostatics. Refinement of Z-DNA with electrostatics leads to a hypothesis for the entropic stabilization of Z-DNA that may partly explain the thermodynamics of converting the B form of DNA to its Z form. Thus, inclusion of electrostatics assists joint neutron/X-ray refinements, especially for placing and orienting hydrogen atoms. PMID:21481775

Modeling of protein binary complexes using structural mass spectrometry data

PubMed Central

Kamal, J.K. Amisha; Chance, Mark R.

2008-01-01

In this article, we describe a general approach to modeling the structure of binary protein complexes using structural mass spectrometry data combined with molecular docking. In the first step, hydroxyl radical mediated oxidative protein footprinting is used to identify residues that experience conformational reorganization due to binding or participate in the binding interface. In the second step, a three-dimensional atomic structure of the complex is derived by computational modeling. Homology modeling approaches are used to define the structures of the individual proteins if footprinting detects significant conformational reorganization as a function of complex formation. A three-dimensional model of the complex is constructed from these binary partners using the ClusPro program, which is composed of docking, energy filtering, and clustering steps. Footprinting data are used to incorporate constraints—positive and/or negative—in the docking step and are also used to decide the type of energy filter—electrostatics or desolvation—in the successive energy-filtering step. By using this approach, we examine the structure of a number of binary complexes of monomeric actin and compare the results to crystallographic data. Based on docking alone, a number of competing models with widely varying structures are observed, one of which is likely to agree with crystallographic data. When the docking steps are guided by footprinting data, accurate models emerge as top scoring. We demonstrate this method with the actin/gelsolin segment-1 complex. We also provide a structural model for the actin/cofilin complex using this approach which does not have a crystal or NMR structure. PMID:18042684

Origin of attraction in p-benzoquinone complexes with benzene and p-hydroquinone.

PubMed

Tsuzuki, Seiji; Uchimaru, Tadafumi; Ono, Taizo

2017-08-30

The origin of the attraction in charge-transfer complexes (a p-hydroquinone-p-benzoquinone complex and benzene complexes with benzoquinone, tetracyanoethylene and Br 2 ) was analyzed using distributed multipole analysis and symmetry-adapted perturbation theory. Both methods show that the dispersion interactions are the primary source of the attraction in these charge-transfer complexes followed by the electrostatic interactions. The natures of the intermolecular interactions in these complexes are close to the π/π interactions of neutral aromatic molecules. The electrostatic interactions play important roles in determining the magnitude of the attraction. The contribution of charge-transfer interactions to the attraction is not large compared with the dispersion interactions in these complexes.

Electrostatic effects on hyaluronic acid configuration

NASA Astrophysics Data System (ADS)

Berezney, John; Saleh, Omar

2015-03-01

In systems of polyelectrolytes, such as solutions of charged biopolymers, the electrostatic repulsion between charged monomers plays a dominant role in determining the molecular conformation. Altering the ionic strength of the solvent thus affects the structure of such a polymer. Capturing this electrostatically-driven structural dependence is important for understanding many biological systems. Here, we use single molecule manipulation experiments to collect force-extension behavior on hyaluronic acid (HA), a polyanion which is a major component of the extracellular matrix in all vertebrates. By measuring HA elasticity in a variety of salt conditions, we are able to directly assess the contribution of electrostatics to the chain's self-avoidance and local stiffness. Similar to recent results from our group on single-stranded nucleic acids, our data indicate that HA behaves as a swollen chain of electrostatic blobs, with blob size proportional to the solution Debye length. Our data indicate that the chain structure within the blob is not worm-like, likely due to long-range electrostatic interactions. We discuss potential models of this effect.

A unified electrostatic and cavitation model for first-principles molecular dynamics in solution

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

Scherlis, D A; Fattebert, J; Gygi, F

2005-11-14

The electrostatic continuum solvent model developed by Fattebert and Gygi is combined with a first-principles formulation of the cavitation energy based on a natural quantum-mechanical definition for the surface of a solute. Despite its simplicity, the cavitation contribution calculated by this approach is found to be in remarkable agreement with that obtained by more complex algorithms relying on a large set of parameters. The model allows for very efficient Car-Parrinello simulations of finite or extended systems in solution, and demonstrates a level of accuracy as good as that of established quantum-chemistry continuum solvent methods. They apply this approach to themore » study of tetracyanoethylene dimers in dichloromethane, providing valuable structural and dynamical insights on the dimerization phenomenon.« less

Spontaneous polarization induced electric field in zinc oxide nanowires and nanostars

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

Farid, S., E-mail: sfarid3@uic.edu; Choi, M.; Datta, D.

We report on the detection mechanism of spontaneous polarization using electrostatic force microscopy in zinc oxide nanowires and nanostars grown by vapor-liquid-solid technique. Optical and structural properties are investigated in detail to understand the complex ZnO nanostructures comprehensively. Calculations are carried out to estimate the electric field from the change in interleave amplitude induced by the electrostatic force due to the spontaneous polarization effects. Attraction of the probe between the tip and the sample varies for different structures with a stronger attraction for nanostars as compared to nanowires. Strength of electric field is dependent on the orientation of nanowires andmore » nanostars c-axis with measured magnitude of electric field to be ∼10{sup 7 }V/m and 10{sup 8 }V/m respectively. This technique presents a unique detection mechanism of built-in spontaneous polarization and electric field from polar ZnO nanowires with applications in voltage gated ion channels, nano-bio interfaces, optoelectronic and photonic devices.« less

Two heads are better than one: crystal structure of the insect derived double domain Kazal inhibitor rhodniin in complex with thrombin.

PubMed

van de Locht, A; Lamba, D; Bauer, M; Huber, R; Friedrich, T; Kröger, B; Höffken, W; Bode, W

1995-11-01

Rhodniin is a highly specific inhibitor of thrombin isolated from the assassin bug Rhodnius prolixus. The 2.6 Angstrum crystal structure of the non-covalent complex between recombinant rhodniin and bovine alpha-thrombin reveals that the two Kazal-type domains of rhodniin bind to different sites of thrombin. The amino-terminal domain binds in a substrate-like manner to the narrow active-site cleft of thrombin; the imidazole group of the P1 His residue extends into the S1 pocket to form favourable hydrogen/ionic bonds with Asp189 at its bottom, and additionally with Glu192 at its entrance. The carboxy-terminal domain, whose distorted reactive-site loop cannot adopt the canonical conformation, docks to the fibrinogen recognition exosite via extensive electrostatic interactions. The rather acidic polypeptide linking the two domains is displaced from the thrombin surface, with none of its residues involved in direct salt bridges with thrombin. The tight (Ki = 2 x 10(-13) M) binding of rhodniin to thrombin is the result of the sum of steric and charge complementarity of the amino-terminal domain towards the active-site cleft, and of the electrostatic interactions between the carboxy-terminal domain and the exosite.

Vibrational Stark effect spectroscopy reveals complementary electrostatic fields created by protein-protein binding at the interface of Ras and Ral.

PubMed

Walker, David M; Hayes, Ellen C; Webb, Lauren J

2013-08-07

Electrostatic fields at the interface of the GTPase H-Ras (Ras) docked with the Ras binding domain of the protein Ral guanine nucleoside dissociation stimulator (Ral) were measured with vibrational Stark effect (VSE) spectroscopy. Nine residues on the surface of Ras that participate in the protein-protein interface were systematically mutated to cysteine and subsequently converted to cyanocysteine in order to introduce a nitrile VSE probe into the protein-protein interface. The absorption energy of the nitrile was measured both on the surface of Ras in its monomeric state, then after incubation with the Ras binding domain of Ral to form the docked complex. Boltzmann-weighted structural snapshots of the nitrile-labeled Ras protein were generated both in monomeric and docked configurations from molecular dynamics simulations using enhanced sampling of the cyanocysteine side chain's χ2 dihedral angle. These snapshots were used to determine that on average, most of the nitrile probes were aligned along the Ras surface, parallel to the Ras-Ral interface. The average solvent-accessible surface areas (SASA) of the cyanocysteine side chain were found to be <60 Å(2) for all measured residues, and was not significantly different whether the nitrile was on the surface of the Ras monomer or immersed in the docked complex. Changes in the absorption energy of the nitrile probe at nine positions along the Ras-Ral interface were compared to results of a previous study examining this interface with Ral-based probes, and found a pattern of low electrostatic field in the core of the interface surrounded by a ring of high electrostatic field around the perimeter of the interface. These data are used to rationalize several puzzling features of the Ras-Ral interface.

Review on the Modeling of Electrostatic MEMS

PubMed Central

Chuang, Wan-Chun; Lee, Hsin-Li; Chang, Pei-Zen; Hu, Yuh-Chung

2010-01-01

Electrostatic-driven microelectromechanical systems devices, in most cases, consist of couplings of such energy domains as electromechanics, optical electricity, thermoelectricity, and electromagnetism. Their nonlinear working state makes their analysis complex and complicated. This article introduces the physical model of pull-in voltage, dynamic characteristic analysis, air damping effect, reliability, numerical modeling method, and application of electrostatic-driven MEMS devices. PMID:22219707

Binding regularities in complexes of transcription factors with operator DNA: homeodomain family.

PubMed

Chirgadze, Yu N; Zheltukhin, E I; Polozov, R V; Sivozhelezov, V S; Ivanov, V V

2009-06-01

In order to disclose general regularities of binding in homeodomain-DNA complexes we considered five of them and extended the observed regularities over the entire homeodomain family. The five complexes have been selected by similarity of protein structures and patterns of contacting residues. Their long range interactions and interfaces were compared. The long-range stage of the recognition process was characterized by electrostatic potentials about 5 Angstrom away from molecular surfaces of protein or DNA. For proteins, clear positive potential is displayed only at the side contacting the DNA. The double-chained DNA molecule displays a rather strong negative potential, especially in their grooves. Thus, a functional role of electrostatics is a guiding of the protein into the DNA major groove, so the protein and DNA could form a loose non-specific complex. At the close-range stage, neutralization of the phosphate charges by positively charged residues is necessary for decreasing the strong electrostatic potential of DNA, allowing nucleotide bases to participate in the formation of protein-DNA atomic contacts in the interface. The recognizing alpha-helix of protein was shown to form both invariant and variable groups of contacts with DNA by means of certain specific side groups. The invariant contacts included highly specific protein-DNA hydrogen bonds between asparagine and adenine, nonpolar contacts of hydrophobic amino acids serving as a stereochemical barrier for fixing the protein factor on DNA, and an interface cluster of water molecules providing local conformational mobility necessary for the dissociation process. There is a unique water molecule within the interface that is conservative and located at the interface center. Invariant contacts of the proteins are mostly formed with the TAAT motif of the promoter DNA forward strand. While the invariant contacts specify the family of homeodomains, the variable contacts that are formed with the reverse strand of DNA provide specificity of individual complexes within the homeodomain family.

Electrostatic complementarity at protein/protein interfaces.

PubMed

McCoy, A J; Chandana Epa, V; Colman, P M

1997-05-02

Calculation of the electrostatic potential of protein-protein complexes has led to the general assertion that protein-protein interfaces display "charge complementarity" and "electrostatic complementarity". In this study, quantitative measures for these two terms are developed and used to investigate protein-protein interfaces in a rigorous manner. Charge complementarity (CC) was defined using the correlation of charges on nearest neighbour atoms at the interface. All 12 protein-protein interfaces studied had insignificantly small CC values. Therefore, the term charge complementarity is not appropriate for the description of protein-protein interfaces when used in the sense measured by CC. Electrostatic complementarity (EC) was defined using the correlation of surface electrostatic potential at protein-protein interfaces. All twelve protein-protein interfaces studied had significant EC values, and thus the assertion that protein-protein association involves surfaces with complementary electrostatic potential was substantially confirmed. The term electrostatic complementarity can therefore be used to describe protein-protein interfaces when used in the sense measured by EC. Taken together, the results for CC and EC demonstrate the relevance of the long-range effects of charges, as described by the electrostatic potential at the binding interface. The EC value did not partition the complexes by type such as antigen-antibody and proteinase-inhibitor, as measures of the geometrical complementarity at protein-protein interfaces have done. The EC value was also not directly related to the number of salt bridges in the interface, and neutralisation of these salt bridges showed that other charges also contributed significantly to electrostatic complementarity and electrostatic interactions between the proteins. Electrostatic complementarity as defined by EC was extended to investigate the electrostatic similarity at the surface of influenza virus neuraminidase where the epitopes of two monoclonal antibodies, NC10 and NC41, overlap. Although NC10 and NC41 both have quite high values of EC for their interaction with neuraminidase, the similarity in electrostatic potential generated by the two on the overlapping region of the epitopes is insignificant. Thus, it is possible for two antibodies to recognise the electrostatic surface of a protein in dissimilar ways.

Electrostatic effects in unfolded staphylococcal nuclease

PubMed Central

Fitzkee, Nicholas C.; García-Moreno E, Bertrand

2008-01-01

Structure-based calculations of pK a values and electrostatic free energies of proteins assume that electrostatic effects in the unfolded state are negligible. In light of experimental evidence showing that this assumption is invalid for many proteins, and with increasing awareness that the unfolded state is more structured and compact than previously thought, a detailed examination of electrostatic effects in unfolded proteins is warranted. Here we address this issue with structure-based calculations of electrostatic interactions in unfolded staphylococcal nuclease. The approach involves the generation of ensembles of structures representing the unfolded state, and calculation of Coulomb energies to Boltzmann weight the unfolded state ensembles. Four different structural models of the unfolded state were tested. Experimental proton binding data measured with a variant of nuclease that is unfolded under native conditions were used to establish the validity of the calculations. These calculations suggest that weak Coulomb interactions are an unavoidable property of unfolded proteins. At neutral pH, the interactions are too weak to organize the unfolded state; however, at extreme pH values, where the protein has a significant net charge, the combined action of a large number of weak repulsive interactions can lead to the expansion of the unfolded state. The calculated pK a values of ionizable groups in the unfolded state are similar but not identical to the values in small peptides in water. These studies suggest that the accuracy of structure-based calculations of electrostatic contributions to stability cannot be improved unless electrostatic effects in the unfolded state are calculated explicitly. PMID:18227429

Structure and Bonding in Uranyl(VI) Peroxide and Crown Ether Complexes; Comparison of Quantum Chemical and Experimental Data.

PubMed

Vallet, Valérie; Grenthe, Ingmar

2017-12-18

The structure, chemical bonding, and thermodynamics of alkali ions in M[12-crown-4] + , M[15-crown-5] + , and M[18-crown-6] + , M[UO 2 (O 2 )(OH 2 ) 2 ] + 4,5 , and M[UO 2 (O 2 )(OH)(OH 2 )] n 1-n (n = 4, 5) complexes have been explored by using quantum chemical (QC) calculations at the ab initio level. The chemical bonding has been studied in the gas phase in order to eliminate solvent effects. QTAIM analysis demonstrates features that are very similar in all complexes and typical for electrostatic M-O bonds, but with the M-O bonds in the uranyl peroxide systems about 20 kJ mol -1 stronger than in the corresponding crown ether complexes. The regular decrease in bond strength with increasing M-O bond distance is consistent with predominantly electrostatic contributions. Energy decomposition of the reaction energies in the gas phase and solvent demonstrates that the predominant component of the total attractive (ΔE elec + ΔE orb ) energy contribution is the electrostatic component. There are no steric constraints for coordination of large cations to small rings, because the M + ions are located outside the ring plane, [O n ], formed by the oxygen donors in the ligands; coordination of ions smaller than the ligand cavity results in longer than normal M-O distances or in a change in the number of bonds, both resulting in weaker complexes. The Gibbs energies, enthalpies, and entropies of reaction calculated using the conductor-like screening model, COSMO, to account for solvent effects deviate significantly from experimental values in water, while those in acetonitrile are in much better agreement. Factors that might affect the selectivity are discussed, but our conclusion is that present QC methods are not accurate enough to describe the rather small differences in selectivity, which only amount to 5-10 kJ mol -1 . We can, however, conclude on the basis of QC and experimental data that M[crown ether] + complexes in the strongly coordinating water solvent are of outer-sphere type, [M(OH 2 ) n + ][crown ether], while those in weakly coordinating acetonitrile are of inner-sphere type, [M-crown ether] + . The observation that the M[UO 2 (O 2 )(OH)(OH 2 )] n 1-n complexes are more stable in solution than those of M[crown ether] + is an effect of the different charges of the rings.

Nanoscale Structure and Interaction of Compact Assemblies of Carbon Nano-Materials

NASA Astrophysics Data System (ADS)

Timsina, Raju; Qiu, Xiangyun

Carbon-based nano-materials (CNM) are a diverse family of multi-functional materials under research and development world wide. Our work is further motivated by the predictive power of the physical understanding of the underlying structure-interaction-function relationships. Here we present results form recent studies of the condensed phases of several model CNMs in complexation with biologically derived molecules. Specifically, we employ X-ray diffraction (XRD) to determine nanoscale structures and use the osmotic stress method to quantify their interactions. The systems under investigation are dsDNA-dispersed carbon nanotubes (dsDNA-CNT), bile-salt-dispersed carbon nanotubes, and surfactant-assisted assemblies of graphene oxides. We found that salt and molecular crowding are both effective in condensing CNMs but the resultant structures show disparate phase behaviors. The molecular interactions driving the condensation/assembly sensitively depend on the nature of CNM complex surface chemistry and range from hydrophobic to electrostatic to entropic forces.

Probing the Energetics of Dynactin Filament Assembly and the Binding of Cargo Adaptor Proteins Using Molecular Dynamics Simulation and Electrostatics-Based Structural Modeling.

PubMed

Zheng, Wenjun

2017-01-10

Dynactin, a large multiprotein complex, binds with the cytoplasmic dynein-1 motor and various adaptor proteins to allow recruitment and transportation of cellular cargoes toward the minus end of microtubules. The structure of the dynactin complex is built around an actin-like minifilament with a defined length, which has been visualized in a high-resolution structure of the dynactin filament determined by cryo-electron microscopy (cryo-EM). To understand the energetic basis of dynactin filament assembly, we used molecular dynamics simulation to probe the intersubunit interactions among the actin-like proteins, various capping proteins, and four extended regions of the dynactin shoulder. Our simulations revealed stronger intersubunit interactions at the barbed and pointed ends of the filament and involving the extended regions (compared with the interactions within the filament), which may energetically drive filament termination by the capping proteins and recruitment of the actin-like proteins by the extended regions, two key features of the dynactin filament assembly process. Next, we modeled the unknown binding configuration among dynactin, dynein tails, and a number of coiled-coil adaptor proteins (including several Bicaudal-D and related proteins and three HOOK proteins), and predicted a key set of charged residues involved in their electrostatic interactions. Our modeling is consistent with previous findings of conserved regions, functional sites, and disease mutations in the adaptor proteins and will provide a structural framework for future functional and mutational studies of these adaptor proteins. In sum, this study yielded rich structural and energetic information about dynactin and associated adaptor proteins that cannot be directly obtained from the cryo-EM structures with limited resolutions.

Electrostatics determine vibrational frequency shifts in hydrogen bonded complexes.

PubMed

Dey, Arghya; Mondal, Sohidul Islam; Sen, Saumik; Ghosh, Debashree; Patwari, G Naresh

2014-12-14

The red-shifts in the acetylenic C-H stretching vibration of C-H∙∙∙X (X = O, N) hydrogen-bonded complexes increase with an increase in the basicity of the Lewis base. Analysis of various components of stabilization energy suggests that the observed red-shifts are correlated with the electrostatic component of the stabilization energy, while the dispersion modulates the stabilization energy.

Taking the Next Step with Halogenated Olefins: Microwave Spectroscopy and Molecular Structures of - and Chloro-Trifluoro Propenes and Their Complexes with the Argon Atom

NASA Astrophysics Data System (ADS)

Marshall, Mark D.; Leung, Helen O.; Wronkovich, Miles A.; Tracy, Megan E.; Hoque, Laboni; Randy-Cofie, Allison M.; Dao, Alina K.

2017-06-01

The determination of the structures of heterodimers of haloethylenes with protic acids has provided a wealth of information and a few surprises concerning intermolecular forces and the sometimes cooperative and sometimes competing effects of electrostatic, steric, and dispersion forces. In seeking to apply this knowledge to larger systems with a wider variety of possible interactions and binding sites, we extend the carbon chain by one atom via the addition of a trifluoromethyl moeity. As a first step the microwave rotational spectra of the halopropene monomers, 2,3,3,3-tetrafluoropropene, 2-chloro-3,3,3-trifluoropropene, (E)-1-chloro-3,3,3-trifluoropropene, and (Z)-1-chloro-3,3,3-trifluoropropene, and their complexes with the argon atom are obtained and analyzed to obtain molecular structures.

Influence of strain relaxation in axial [Formula: see text] nanowire heterostructures on their electronic properties.

PubMed

Marquardt, Oliver; Krause, Thilo; Kaganer, Vladimir; Martín-Sánchez, Javier; Hanke, Michael; Brandt, Oliver

2017-05-26

We present a systematic theoretical study of the influence of elastic strain relaxation on the built-in electrostatic potentials and the electronic properties of axial [Formula: see text] nanowire (NW) heterostructures. Our simulations reveal that for a sufficiently large ratio between the thickness of the [Formula: see text] disk and the diameter of the NW, the elastic relaxation leads to a significant reduction of the built-in electrostatic potential in comparison to a planar system of similar layer thickness and In content. In this case, the ground state transition energies approach constant values with increasing thickness of the disk and only depend on the In content, a behavior usually associated to that of a quantum well free of built-in electrostatic potentials. We show that the structures under consideration are by no means field-free, and the built-in potentials continue to play an important role even for ultrathin NWs. In particular, strain and the resulting polarization potentials induce complex confinement features of electrons and holes, which depend on the In content, shape, and dimensions of the heterostructure.

Structural and biophysical analysis of interactions between cod and human uracil-DNA N-glycosylase (UNG) and UNG inhibitor (Ugi)

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

Assefa, Netsanet Gizaw; Niiranen, Laila; University of Turku, FIN-20014 Turku

2014-08-01

A structural and biophysical study of the interactions between cod and human uracil-DNA N-glycosylase (UNG) and their inhibitor Ugi is presented. The stronger interaction between cod UNG and Ugi can be explained by a greater positive electrostatic surface potential. Uracil-DNA N-glycosylase from Atlantic cod (cUNG) shows cold-adapted features such as high catalytic efficiency, a low temperature optimum for activity and reduced thermal stability compared with its mesophilic homologue human UNG (hUNG). In order to understand the role of the enzyme–substrate interaction related to the cold-adapted properties, the structure of cUNG in complex with a bacteriophage encoded natural UNG inhibitor (Ugi)more » has been determined. The interaction has also been analyzed by isothermal titration calorimetry (ITC). The crystal structure of cUNG–Ugi was determined to a resolution of 1.9 Å with eight complexes in the asymmetric unit related through noncrystallographic symmetry. A comparison of the cUNG–Ugi complex with previously determined structures of UNG–Ugi shows that they are very similar, and confirmed the nucleotide-mimicking properties of Ugi. Biophysically, the interaction between cUNG and Ugi is very strong and shows a binding constant (K{sub b}) which is one order of magnitude larger than that for hUNG–Ugi. The binding of both cUNG and hUNG to Ugi was shown to be favoured by both enthalpic and entropic forces; however, the binding of cUNG to Ugi is mainly dominated by enthalpy, while the entropic term is dominant for hUNG. The observed differences in the binding properties may be explained by an overall greater positive electrostatic surface potential in the protein–Ugi interface of cUNG and the slightly more hydrophobic surface of hUNG.« less

Branches of electrostatic turbulence inside solitary plasma structures in the auroral ionosphere

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

Golovchanskaya, Irina V.; Kozelov, Boris V.; Chernyshov, Alexander A.

2014-08-15

The excitation of electrostatic turbulence inside space-observed solitary structures is a central topic of this exposition. Three representative solitary structures observed in the topside auroral ionosphere as large-amplitude nonlinear signatures in the electric field and magnetic-field-aligned current on the transverse scales of ∼10{sup 2}–10{sup 3} m are evaluated by the theories of electrostatic wave generation in inhomogeneous background configurations. A quantitative analysis shows that the structures are, in general, effective in destabilizing the inhomogeneous energy-density-driven (IEDD) waves, as well as of the ion acoustic waves modified by a shear in the parallel drift of ions. It is demonstrated that the dominatingmore » branch of the electrostatic turbulence is determined by the interplay of various driving sources inside a particular solitary structure. The sources do not generally act in unison, so that their common effect may be inhibiting for excitation of electrostatic waves of a certain type. In the presence of large magnetic-field-aligned current, which is not correlated to the inhomogeneous electric field inside the structure, the ion-acoustic branch becomes dominating. In other cases, the IEDD instability is more central.« less

Structural phase transition in monolayer MoTe2 driven by electrostatic doping

NASA Astrophysics Data System (ADS)

Wang, Ying; Xiao, Jun; Zhu, Hanyu; Li, Yao; Alsaid, Yousif; Fong, King Yan; Zhou, Yao; Wang, Siqi; Shi, Wu; Wang, Yuan; Zettl, Alex; Reed, Evan J.; Zhang, Xiang

2017-10-01

Monolayers of transition-metal dichalcogenides (TMDs) exhibit numerous crystal phases with distinct structures, symmetries and physical properties. Exploring the physics of transitions between these different structural phases in two dimensions may provide a means of switching material properties, with implications for potential applications. Structural phase transitions in TMDs have so far been induced by thermal or chemical means; purely electrostatic control over crystal phases through electrostatic doping was recently proposed as a theoretical possibility, but has not yet been realized. Here we report the experimental demonstration of an electrostatic-doping-driven phase transition between the hexagonal and monoclinic phases of monolayer molybdenum ditelluride (MoTe2). We find that the phase transition shows a hysteretic loop in Raman spectra, and can be reversed by increasing or decreasing the gate voltage. We also combine second-harmonic generation spectroscopy with polarization-resolved Raman spectroscopy to show that the induced monoclinic phase preserves the crystal orientation of the original hexagonal phase. Moreover, this structural phase transition occurs simultaneously across the whole sample. This electrostatic-doping control of structural phase transition opens up new possibilities for developing phase-change devices based on atomically thin membranes.

The role of positively charged amino acids and electrostatic interactions in the complex of U1A protein and U1 hairpin II RNA

PubMed Central

Law, Michael J.; Linde, Michael E.; Chambers, Eric J.; Oubridge, Chris; Katsamba, Phinikoula S.; Nilsson, Lennart; Haworth, Ian S.; Laird-Offringa, Ite A.

2006-01-01

Previous kinetic investigations of the N-terminal RNA recognition motif (RRM) domain of spliceosomal protein U1A, interacting with its RNA target U1 hairpin II, provided experimental evidence for a ‘lure and lock’ model of binding in which electrostatic interactions first guide the RNA to the protein, and close range interactions then lock the two molecules together. To further investigate the ‘lure’ step, here we examined the electrostatic roles of two sets of positively charged amino acids in U1A that do not make hydrogen bonds to the RNA: Lys20, Lys22 and Lys23 close to the RNA-binding site, and Arg7, Lys60 and Arg70, located on ‘top’ of the RRM domain, away from the RNA. Surface plasmon resonance-based kinetic studies, supplemented with salt dependence experiments and molecular dynamics simulation, indicate that Lys20 predominantly plays a role in association, while nearby residues Lys22 and Lys23 appear to be at least as important for complex stability. In contrast, kinetic analyses of residues away from the RNA indicate that they have a minimal effect on association and stability. Thus, well-positioned positively charged residues can be important for both initial complex formation and complex maintenance, illustrating the multiple roles of electrostatic interactions in protein–RNA complexes. PMID:16407334

New Cu (II), Co(II) and Ni(II) complexes of chalcone derivatives: Synthesis, X-ray crystal structure, electrochemical properties and DFT computational studies

NASA Astrophysics Data System (ADS)

Tabti, Salima; Djedouani, Amel; Aggoun, Djouhra; Warad, Ismail; Rahmouni, Samra; Romdhane, Samir; Fouzi, Hosni

2018-03-01

The reaction of nickel(II), copper(II) and cobalt(II) with 4-hydroxy-3-[(2E)-3-(1H-indol-3-yl)prop-2-enoyl]-6-methyl-2H-pyran-2-one (HL) leads to a series of new complexes: Ni(L)2(NH3), Cu(L)2(DMF)2 and Co(L)2(H2O). The crystal structure of the Cu(L)2(DMF)2 complex have been determined by X-ray diffraction methods. The Cu(II) lying on an inversion centre is coordinated to six oxygen atoms forming an octahedral elongated. Additionally, the electrochemical behavior of the metal complexes were investigated by cyclic voltammetry at a glassy carbon electrode (GC) in CH3CN solutions, showing the quasi-reversible redox process ascribed to the reduction of the MII/MI couples. The X-ray single crystal structure data of the complex was matched excellently with the optimized monomer structure of the desired compound; Hirschfeld surface analysis supported the packed crystal lattice 3D network intermolecular forces. HOMO/LUMO energy level and the global reactivity descriptors quantum parameters are also calculated. The electrophilic and nucleophilic potions in the complex surface are theoretically evaluated by molecular electrostatic potential and Mulliken atomic charges analysis.

Composition and structure of whey protein/gum arabic coacervates.

PubMed

Weinbreck, F; Tromp, R H; de Kruif, C G

2004-01-01

Complex coacervation in whey protein/gum arabic (WP/GA) mixtures was studied as a function of three main key parameters: pH, initial protein to polysaccharide mixing ratio (Pr:Ps)(ini), and ionic strength. Previous studies had already revealed under which conditions a coacervate phase was obtained. This study is aimed at understanding how these parameters influence the phase separation kinetics, the coacervate composition, and the internal coacervate structure. At a defined (Pr:Ps)(ini), an optimum pH of complex coacervation was found (pH(opt)), at which the strength of electrostatic interaction was maximum. For (Pr:Ps)(ini) = 2:1, the phase separation occurred the fastest and the final coacervate volume was the largest at pH(opt) = 4.0. The composition of the coacervate phase was determined after 48 h of phase separation and revealed that, at pH(opt), the coacervate phase was the most concentrated. Varying the (Pr:Ps)(ini) shifted the pH(opt) to higher values when (Pr:Ps)(ini) was increased and to lower values when (Pr:Ps)(ini) was decreased. This phenomenon was due to the level of charge compensation of the WP/GA complexes. Finally, the structure of the coacervate phase was studied with small-angle X-ray scattering (SAXS). SAXS data confirmed that at pH(opt) the coacervate phase was dense and structured. Model calculations revealed that the structure factor of WP induced a peak at Q = 0.7 nm(-1), illustrating that the coacervate phase was more structured, inducing the stronger correlation length of WP molecules. When the pH was changed to more acidic values, the correlation peak faded away, due to a more open structure of the coacervate. A shoulder in the scattering pattern of the coacervates was visible at small Q. This peak was attributed to the presence of residual charges on the GA. The peak intensity was reduced when the strength of interaction was increased, highlighting a greater charge compensation of the polyelectrolyte. Finally, increasing the ionic strength led to a less concentrated, a more heterogeneous, and a less structured coacervate phase, induced by the screening of the electrostatic interactions.

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.

Quantitative tests of a reconstitution model for RNA folding thermodynamics and kinetics.

PubMed

Bisaria, Namita; Greenfeld, Max; Limouse, Charles; Mabuchi, Hideo; Herschlag, Daniel

2017-09-12

Decades of study of the architecture and function of structured RNAs have led to the perspective that RNA tertiary structure is modular, made of locally stable domains that retain their structure across RNAs. We formalize a hypothesis inspired by this modularity-that RNA folding thermodynamics and kinetics can be quantitatively predicted from separable energetic contributions of the individual components of a complex RNA. This reconstitution hypothesis considers RNA tertiary folding in terms of ΔG align , the probability of aligning tertiary contact partners, and ΔG tert , the favorable energetic contribution from the formation of tertiary contacts in an aligned state. This hypothesis predicts that changes in the alignment of tertiary contacts from different connecting helices and junctions (ΔG HJH ) or from changes in the electrostatic environment (ΔG +/- ) will not affect the energetic perturbation from a mutation in a tertiary contact (ΔΔG tert ). Consistent with these predictions, single-molecule FRET measurements of folding of model RNAs revealed constant ΔΔG tert values for mutations in a tertiary contact embedded in different structural contexts and under different electrostatic conditions. The kinetic effects of these mutations provide further support for modular behavior of RNA elements and suggest that tertiary mutations may be used to identify rate-limiting steps and dissect folding and assembly pathways for complex RNAs. Overall, our model and results are foundational for a predictive understanding of RNA folding that will allow manipulation of RNA folding thermodynamics and kinetics. Conversely, the approaches herein can identify cases where an independent, additive model cannot be applied and so require additional investigation.

Brownian dynamics simulations of interactions between aldolase and G- or F-actin.

PubMed Central

Ouporov, I V; Knull, H R; Thomasson, K A

1999-01-01

Compartmentation of proteins in cells is important to proper cell function. Interactions of F-actin and glycolytic enzymes is one mechanism by which glycolytic enzymes can compartment. Brownian dynamics (BD) simulations of the binding of the muscle form of the glycolytic enzyme fructose-1,6-bisphosphate aldolase (aldolase) to F- or G-actin provide first-encounter snapshots of these interactions. Using x-ray structures of aldolase, G-actin, and three-dimensional models of F-actin, the electrostatic potential about each protein was predicted by solving the linearized Poisson-Boltzmann equation for use in BD simulations. The BD simulations provided solution complexes of aldolase with F- or G-actin. All complexes demonstrate the close contacts between oppositely charged regions of the protein surfaces. Positively charged surface regions of aldolase (residues Lys 13, 27, 288, 293, and 341 and Arg 257) are attracted to the negatively charged amino terminus (Asp 1 and Glu 2 and 4) and other patches (Asp 24, 25, and 363 and Glu 361, 364, 99, and 100) of actin subunits. According to BD results, the most important factor for aldolase binding to actin is the quaternary structure of aldolase and actin. Two pairs of adjacent aldolase subunits greatly add to the positive electrostatic potential of each other creating a region of attraction for the negatively charged subdomain 1 of the actin subunit that is exposed to solvent in the quaternary F-actin structure. PMID:9876119

Electrostatic Steering Accelerates C3d:CR2 Association.

PubMed

Mohan, Rohith R; Huber, Gary A; Morikis, Dimitrios

2016-08-25

Electrostatic effects are ubiquitous in protein interactions and are found to be pervasive in the complement system as well. The interaction between complement fragment C3d and complement receptor 2 (CR2) has evolved to become a link between innate and adaptive immunity. Electrostatic interactions have been suggested to be the driving factor for the association of the C3d:CR2 complex. In this study, we investigate the effects of ionic strength and mutagenesis on the association of C3d:CR2 through Brownian dynamics simulations. We demonstrate that the formation of the C3d:CR2 complex is ionic strength-dependent, suggesting the presence of long-range electrostatic steering that accelerates the complex formation. Electrostatic steering occurs through the interaction of an acidic surface patch in C3d and the positively charged CR2 and is supported by the effects of mutations within the acidic patch of C3d that slow or diminish association. Our data are in agreement with previous experimental mutagenesis and binding studies and computational studies. Although the C3d acidic patch may be locally destabilizing because of unfavorable Coulombic interactions of like charges, it contributes to the acceleration of association. Therefore, acceleration of function through electrostatic steering takes precedence to stability. The site of interaction between C3d and CR2 has been the target for delivery of CR2-bound nanoparticle, antibody, and small molecule biomarkers, as well as potential therapeutics. A detailed knowledge of the physicochemical basis of C3d:CR2 association may be necessary to accelerate biomarker and drug discovery efforts.

Electrostatic orientation of the electron-transfer complex between plastocyanin and cytochrome c.

PubMed

Roberts, V A; Freeman, H C; Olson, A J; Tainer, J A; Getzoff, E D

1991-07-15

To understand the specificity and efficiency of protein-protein interactions promoting electron transfer, we evaluated the role of electrostatic forces in precollision orientation by the development of two new methods, computer graphics alignment of protein electrostatic fields and a systematic orientational search of intermolecular electrostatic energies for two proteins at present separation distances. We applied these methods to the plastocyanin/cytochrome c interaction, which is faster than random collision, but too slow for study by molecular dynamics techniques. Significant electrostatic potentials were concentrated on one-fourth (969 A2) of the plastocyanin surface, with the greatest negative potential centered on the Tyr-83 hydroxyl within the acidic patch, and on one-eighth (632 A2) of the cytochrome c surface, with the greatest positive potential centered near the exposed heme edge. Coherent electrostatic fields occurred only over these regions, suggesting that local, rather than global, charge complementarity controls productive recognition. The three energetically favored families of pre-collision orientations all directed the positive region surrounding the heme edge of cytochrome c toward the acidic patch of plastocyanin but differed in heme plane orientation. Analysis of electrostatic fields, electrostatic energies of precollision orientations with 12 and 6 A separation distances, and surface topographies suggested that the favored orientations should converge to productive complexes promoting a single electron-transfer pathway from the cytochrome c heme edge to Tyr-83 of plastocyanin. Direct interactions of the exposed Cu ligand in plastocyanin with the cytochrome c heme edge are not unfavorable sterically or electrostatically but should occur no faster than randomly, indicating that this is not the primary pathway for electron transfer.

Structure-affinity relationships for the binding of actinomycin D to DNA

NASA Astrophysics Data System (ADS)

Gallego, José; Ortiz, Angel R.; de Pascual-Teresa, Beatriz; Gago, Federico

1997-03-01

Molecular models of the complexes between actinomycin D and 14 different DNA hexamers were built based on the X-ray crystal structure of the actinomycin-d(GAAGCTTC)2 complex. The DNA sequences included the canonical GpC binding step flanked by different base pairs, nonclassical binding sites such as GpG and GpT, and sites containing 2,6-diamino- purine. A good correlation was found between the intermolecular interaction energies calculated for the refined complexes and the relative preferences of actinomycin binding to standard and modified DNA. A detailed energy decomposition into van der Waals and electrostatic components for the interactions between the DNA base pairs and either the chromophore or the peptidic part of the antibiotic was performed for each complex. The resulting energy matrix was then subjected to principal component analysis, which showed that actinomycin D discriminates among different DNA sequences by an interplay of hydrogen bonding and stacking interactions. The structure-affinity relationships for this important antitumor drug are thus rationalized and may be used to advantage in the design of novel sequence-specific DNA-binding agents.

Anharmonic vibrational spectroscopy, NBO charges and global chemical reactivity studies on the charge transfer PDCA-.AHMP+ single crystal using DFT calculations

NASA Astrophysics Data System (ADS)

Faizan, Mohd; Afroz, Ziya; Bhat, Sheeraz Ahmad; Alam, Mohamad Jane; Ahmad, Shabbir; Ahmad, Afaq

2018-04-01

The charge transfer (CT) complex of the 2-amino-4-hydroxy-6-methylpyrimidine and 2,3 pyrazinedicarboxylic acid (PDCA-.AHMP+) was synthesized and its single crystal was grown by solution method. The structure of the crystalline complex has been investigated by single crystal X-ray diffraction (SCXRD). The vibrational features of the complex have been studied with the help of FTIR spectra and DFT computation. The anharmonic corrections in vibrational frequencies are made using the GVPT2 method at B3LYP/6-311++G(d,p) level of theory. The frontier molecular orbitals and global chemical reactivity have been calculated to understand the pharmacological aspect of the synthesized crystal. Furthermore, Hirshfeld electrostatic potential (ESP) surface, void space in the crystal structure and natural as well as Mulliken atomic charges are studied.

Experimentally biased model structure of the Hsc70/auxilin complex: Substrate transfer and interdomain structural change

PubMed Central

Gruschus, James M.; Greene, Lois E.; Eisenberg, Evan; Ferretti, James A.

2004-01-01

A model structure of the Hsc70/auxilin complex has been constructed to gain insight into interprotein substrate transfer and ATP hydrolysis induced conformational changes in the multidomain Hsc70 structure. The Hsc70/auxilin system, which is a member of the Hsp70/Hsp40 chaperone system family, uncoats clathrin-coated vesicles in an ATP hydrolysis-driven process. Incorporating previous results from NMR and mutant binding studies, the auxilin J-domain was docked into the Hsc70 ATPase domain lower cleft using rigid backbone/flexible side chain molecular dynamics, and the Hsc70 substrate binding domain was docked by a similar procedure. For comparison, J-domain and substrate binding domain docking sites were obtained by the rigid-body docking programs DOT and ZDOCK, filtered and ranked by the program ClusPro, and relaxed using the same rigid backbone/flexible side chain dynamics. The substrate binding domain sites were assessed in terms of conserved surface complementarity and feasibility in the context of substrate transfer, both for auxilin and another Hsp40 protein, Hsc20. This assessment favors placement of the substrate binding domain near D152 on the ATPase domain surface adjacent to the J-domain invariant HPD segment, with the Hsc70 interdomain linker in the lower cleft. Examining Hsc70 interdomain energetics, we propose that long-range electrostatic interactions, perhaps due to a difference in the pKa values of bound ATP and ADP, could play a major role in the structural change induced by ATP hydrolysis. Interdomain electrostatic interactions also appear to play a role in stimulation of ATPase activity due to J-domain binding and substrate binding by Hsc70. PMID:15273304

Biofilm formation and local electrostatic force characteristics of Escherichia coli O157:H7 observed by electrostatic force microscopy

NASA Astrophysics Data System (ADS)

Oh, Y. J.; Jo, W.; Yang, Y.; Park, S.

2007-04-01

The authors report growth media dependence of electrostatic force characteristics in Escherichia coli O157:H7 biofilm through local measurement by electrostatic force microscopy (EFM). The difference values of electrostatic interaction between the bacterial surface and the abiotic surface show an exponential decay behavior during biofilm development. In the EFM data, the biofilm in the low nutrient media shows a faster decay than the biofilm in the rich media. The surface potential in the bacterial cells was changed from 957to149mV. Local characterization of extracellular materials extracted from the bacteria reveals the progress of the biofilm formation and functional complexities.

Review: Electrostatically actuated nanobeam-based nanoelectromechanical switches – materials solutions and operational conditions

PubMed Central

Jasulaneca, Liga; Kosmaca, Jelena; Meija, Raimonds; Andzane, Jana

2018-01-01

This review summarizes relevant research in the field of electrostatically actuated nanobeam-based nanoelectromechanical (NEM) switches. The main switch architectures and structural elements are briefly described and compared. Investigation methods that allow for exploring coupled electromechanical interactions as well as studies of mechanically or electrically induced effects are covered. An examination of the complex nanocontact behaviour during various stages of the switching cycle is provided. The choice of the switching element and the electrode is addressed from the materials perspective, detailing the benefits and drawbacks for each. An overview of experimentally demonstrated NEM switching devices is provided, and together with their operational parameters, the reliability issues and impact of the operating environment are discussed. Finally, the most common NEM switch failure modes and the physical mechanisms behind them are reviewed and solutions proposed. PMID:29441272

Interaction and formation mechanism of binary complex between zein and propylene glycol alginate.

PubMed

Sun, Cuixia; Dai, Lei; Gao, Yanxiang

2017-02-10

The anti-solvent co-precipitation method was used to fabricate the zein-propylene glycol alginate (PGA) binary complex with different mass ratios of zein to PGA (20:1, 10:1, 5:1, 2:1 and 1:1) at pH 4.0. Results showed that attractive electrostatic interaction between zein and PGA occurred and negatively charged binary complex with large size and high turbidity was formed due to the charge neutralization. Hydrogen bonding and hydrophobic effects were involved in the interactions between zein and PGA, leading to the changed secondary structure and improved thermal stability of zein. Aggregates in the irregular shape with large size were obviously observed in the AFM images. PGA alone exhibited a fine filamentous network structure, while zein-PGA binary complex showed a rough branch-like pattern and the surface of "branch" was closely adsorbed by lots of spherical zein particles. Q in zein-PGA binary complex dispersions presented the improved photochemical and thermal stability. The potential mechanism of a two-step process was proposed to explain the formation of zein-PGA binary complexes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chirality-selected phase behaviour in ionic polypeptide complexes

DOE PAGES

Perry, Sarah L.; Leon, Lorraine; Hoffmann, Kyle Q.; ...

2015-01-14

In this study, polyelectrolyte complexes present new opportunities for self-assembled soft matter. Factors determining whether the phase of the complex is solid or liquid remain unclear. Ionic polypeptides enable examination of the effects of stereochemistry on complex formation. Here we demonstrate that chirality determines the state of polyelectrolyte complexes, formed from mixing dilute solutions of oppositely charged polypeptides, via a combination of electrostatic and hydrogen-bonding interactions. Fluid complexes occur when at least one of the polypeptides in the mixture is racemic, which disrupts backbone hydrogen-bonding networks. Pairs of purely chiral polypeptides, of any sense, form compact, fibrillar solids with amore » β-sheet structure. Analogous behaviour occurs in micelles formed from polypeptide block copolymers with polyethylene oxide, where assembly into aggregates with either solid or fluid cores, and eventually into ordered phases at high concentrations, is possible. Chirality is an exploitable tool for manipulating material properties in polyelectrolyte complexation.« less

Long-pore Electrostatics in Inward-rectifier Potassium Channels

PubMed Central

Robertson, Janice L.; Palmer, Lawrence G.; Roux, Benoît

2008-01-01

Inward-rectifier potassium (Kir) channels differ from the canonical K+ channel structure in that they possess a long extended pore (∼85 Å) for ion conduction that reaches deeply into the cytoplasm. This unique structural feature is presumably involved in regulating functional properties specific to Kir channels, such as conductance, rectification block, and ligand-dependent gating. To elucidate the underpinnings of these functional roles, we examine the electrostatics of an ion along this extended pore. Homology models are constructed based on the open-state model of KirBac1.1 for four mammalian Kir channels: Kir1.1/ROMK, Kir2.1/IRK, Kir3.1/GIRK, and Kir6.2/KATP. By solving the Poisson-Boltzmann equation, the electrostatic free energy of a K+ ion is determined along each pore, revealing that mammalian Kir channels provide a favorable environment for cations and suggesting the existence of high-density regions in the cytoplasmic domain and cavity. The contribution from the reaction field (the self-energy arising from the dielectric polarization induced by the ion's charge in the complex geometry of the pore) is unfavorable inside the long pore. However, this is well compensated by the electrostatic interaction with the static field arising from the protein charges and shielded by the dielectric surrounding. Decomposition of the static field provides a list of residues that display remarkable correspondence with existing mutagenesis data identifying amino acids that affect conduction and rectification. Many of these residues demonstrate interactions with the ion over long distances, up to 40 Å, suggesting that mutations potentially affect ion or blocker energetics over the entire pore. These results provide a foundation for understanding ion interactions in Kir channels and extend to the study of ion permeation, block, and gating in long, cation-specific pores. PMID:19001143

Binding of an antibody mimetic of the human low density lipoprotein receptor to apolipoprotein E is governed through electrostatic forces. Studies using site-directed mutagenesis and molecular modeling.

PubMed

Raffaï, R; Weisgraber, K H; MacKenzie, R; Rupp, B; Rassart, E; Hirama, T; Innerarity, T L; Milne, R

2000-03-10

Monoclonal antibody 2E8 is specific for an epitope that coincides with the binding site of the low density lipoprotein receptor (LDLR) on human apoE. Its reactivity with apoE variants resembles that of the LDLR: it binds well with apoE3 and poorly with apoE2. The heavy chain complementarity-determining region (CDRH) 2 of 2E8 shows homology to the ligand-binding domain of the LDLR. To define better the structural basis of the 2E8/apoE interaction and particularly the role of electrostatic interactions, we generated and characterized a panel of 2E8 variants. Replacement of acidic residues in the 2E8 CDRHs showed that Asp(52), Glu(53), and Asp(56) are essential for high-affinity binding. Although Asp(31) (CDRH1), Glu(58) (CDRH2), and Asp(97) (CDRH3) did not appear to be critical, the Asp(97) --> Ala variant acquired reactivity with apoE2. A Thr(57) --> Glu substitution increased affinity for both apoE3 and apoE2. The affinities of wild-type 2E8 and variants for apoE varied inversely with ionic strength, suggesting that electrostatic forces contribute to both antigen binding and isoform specificity. We propose a model of the 2E8.apoE immune complex that is based on the 2E8 and apoE crystal structures and that is consistent with the apoE-binding properties of wild-type 2E8 and its variants. Given the similarity between the LDLR and 2E8 in terms of specificity, the LDLR/ligand interaction may also have an important electrostatic component.

Structural Dynamics Investigation of Human Family 1 & 2 Cystatin-Cathepsin L1 Interaction: A Comparison of Binding Modes.

PubMed

Nandy, Suman Kumar; Seal, Alpana

2016-01-01

Cystatin superfamily is a large group of evolutionarily related proteins involved in numerous physiological activities through their inhibitory activity towards cysteine proteases. Despite sharing the same cystatin fold, and inhibiting cysteine proteases through the same tripartite edge involving highly conserved N-terminal region, L1 and L2 loop; cystatins differ widely in their inhibitory affinity towards C1 family of cysteine proteases and molecular details of these interactions are still elusive. In this study, inhibitory interactions of human family 1 & 2 cystatins with cathepsin L1 are predicted and their stability and viability are verified through protein docking & comparative molecular dynamics. An overall stabilization effect is observed in all cystatins on complex formation. Complexes are mostly dominated by van der Waals interaction but the relative participation of the conserved regions varied extensively. While van der Waals contacts prevail in L1 and L2 loop, N-terminal segment chiefly acts as electrostatic interaction site. In fact the comparative dynamics study points towards the instrumental role of L1 loop in directing the total interaction profile of the complex either towards electrostatic or van der Waals contacts. The key amino acid residues surfaced via interaction energy, hydrogen bonding and solvent accessible surface area analysis for each cystatin-cathepsin L1 complex influence the mode of binding and thus control the diverse inhibitory affinity of cystatins towards cysteine proteases.

Influence of Na+ and Mg2+ ions on RNA structures studied with molecular dynamics simulations.

PubMed

Fischer, Nina M; Polêto, Marcelo D; Steuer, Jakob; van der Spoel, David

2018-06-01

The structure of ribonucleic acid (RNA) polymers is strongly dependent on the presence of, in particular Mg2+ cations to stabilize structural features. Only in high-resolution X-ray crystallography structures can ions be identified reliably. Here, we perform molecular dynamics simulations of 24 RNA structures with varying ion concentrations. Twelve of the structures were helical and the others complex folded. The aim of the study is to predict ion positions but also to evaluate the impact of different types of ions (Na+ or Mg2+) and the ionic strength on structural stability and variations of RNA. As a general conclusion Mg2+ is found to conserve the experimental structure better than Na+ and, where experimental ion positions are available, they can be reproduced with reasonable accuracy. If a large surplus of ions is present the added electrostatic screening makes prediction of binding-sites less reproducible. Distinct differences in ion-binding between helical and complex folded structures are found. The strength of binding (ΔG‡ for breaking RNA atom-ion interactions) is found to differ between roughly 10 and 26 kJ/mol for the different RNA atoms. Differences in stability between helical and complex folded structures and of the influence of metal ions on either are discussed.

Complexes of native Ubiquitin and dodecyl sulfate illustrate the nature of hydrophobic and electrostatic interactions in the binding of proteins and surfactants

PubMed Central

Shaw, Bryan F.; Schneider, Grégory F.; Arthanari, Haribabu; Narovlyansky, Max; Moustakas, Demetri; Durazo, Armando; Wagner, Gerhard; Whitesides, George M.

2011-01-01

A previous study, using capillary electrophoresis (CE), reported that six discrete complexes of ubiquitin (UBI) and sodium dodecyl sulfate (SDS) form at different concentrations of SDS along the pathway to unfolding of UBI in solutions of SDS. One complex (which formed between 0.8 and 1.8 mM SDS) consisted of native UBI associated with approximately 11 molecules of SDS. The current study used CE and 15N/13C-1H heteronuclear single quantum coherence (HSQC) NMR spectroscopy to identify residues in folded UBI that associate specifically with SDS at 0.8-1.8 mM SDS, and to correlate these associations with established biophysical and structural properties of this well-characterized protein. The ability of the surface charge and hydrophobicity of folded UBI to affect the association with SDS (at concentrations below the CMC) was studied, using CE, by converting lys-ε-NH3+ to lys-ε-NHCOCH3 groups. According to CE, the acetylation of lysine residues inhibited the binding of 11 SDS ([SDS] < 2 mM) and decreased the number of complexes of composition UBI-(NHAc)8·SDSn that formed on the pathway of unfolding of UBI-(NHAc)8 in SDS. A comparison of 15N-1H HSQC spectra at 0 mM and 1 mM SDS with calculated electrostatic surface potentials of folded UBI (e.g., solutions to the non-linear Poisson-Boltzmann (PB) equation) suggested, however, that SDS binds preferentially to native UBI at hydrophobic residues that are formally neutral (i.e., Leu and Ile), but that have positive electrostatic surface potential (as predicted from solutions to non-linear Poisson-Boltzmann equations); SDS did not uniformly interact with residues that have formal positive charge (e.g., Lys or Arg). Cationic functional groups, therefore, promote the binding of SDS to folded UBI because these groups exert long-range effects on the positive electrostatic surface potential (which extend beyond their own van der Waal’s radii, as predicted from PB theory), and not because cationic groups are necessarily the site of ionic interactions with sulfate groups. Moreover, SDS associated with residues in native UBI without regard to their location in α-helix or β-sheet structure (although residues in hydrogen-bonded loops did not bind SDS). No correlation was observed between the association of an amino acid with SDS and the solvent accessibility of the residue or its rate of amide H/D exchange. This study establishes a few (of perhaps several) factors that control the simultaneous molecular recognition of multiple anionic amphiphiles by a folded cytosolic protein. PMID:21939262

Strong CH/O interactions between polycyclic aromatic hydrocarbons and water: Influence of aromatic system size.

PubMed

Veljković, Dušan Ž

2018-03-01

Energies of CH/O interactions between water molecule and polycyclic aromatic hydrocarbons with a different number of aromatic rings were calculated using ab initio calculations at MP2/cc-PVTZ level. Results show that an additional aromatic ring in structure of polycyclic aromatic hydrocarbons significantly strengthens CH/O interactions. Calculated interaction energies in optimized structures of the most stable tetracene/water complex is -2.27 kcal/mol, anthracene/water is -2.13 kcal/mol and naphthalene/water is -1.97 kcal/mol. These interactions are stronger than CH/O contacts in benzene/water complex (-1.44 kcal/mol) while CH/O contacts in tetracene/water complex are even stronger than CH/O contacts in pyridine/water complexes (-2.21 kcal/mol). Electrostatic potential maps for different polycyclic aromatic hydrocarbons were calculated and used to explain trends in the energies of interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

Theoretical Study on the Complexes of Benzene with Isoelectronic Nitrogen-Containing Heterocycles

PubMed Central

Wang, Weizhou; Hobza, Pavel

2008-01-01

The π–π interactions between benzene and the aromatic nitrogen heterocycles pyridine, pyrimidine, 1,3,5-triazine, 1,2,3-triazine, 1,2,4,5-tetrazine, and 1,2,3,4,5-pentazine are systematically investigated. The T-shaped structures of all complexes studied exhibit a contraction of the C—H bond accompanied by a rather large blue shift (40–52 cm−1) of its stretching frequency, and they are almost isoenergetic with the corresponding displaced-parallel structures at reliable levels of theory. With increasing number of nitrogen atoms in the heterocycle, the geometries, frequencies, energies, percentage of s character at C, and the electron density in the C—H σ antibonding orbital of the complexes all increase or decrease systematically. Decomposition analysis of the total binding energy showed that for all the complexes, the dispersion energy is the dominant attractive contribution, and a rather large attraction originating from electrostatic contribution is compensated by its exchange counterpart. PMID:18389512

Counter anion effect on structural, opto-electronic and charge transport properties of fused π-conjugated imidazolium compound

NASA Astrophysics Data System (ADS)

Vinodha, M.; Senthilkumar, K.

2018-05-01

The structure-activity relationship of fused π-conjugated imidazolium cation with three counter anion molecules, BF4-, CF3SO3- and (CF3SO2)2N-, was studied using electronic structure calculations. The structural, opto-electronic and charge transport properties of these complexes were studied. The charge transfer from π-conjugated imidazolium(I) to counter anion was confirmed in all the studied complexes. Interaction energy varies significantly depending on the counter anion and the stability was found higher for I-BF4 complex than both I-CF3SO3 and I-(CF3SO2)2N complexes. The strong (C-H)+...F- hydrogen bond of length 1.95 Å between fused π-conjugated imidazolium and BF-4 anion is the driving force for the strongest interaction energy in I-BF4 complex. The energy decomposition analysis confirms that the interaction between imidazolium and counter anion is mainly driven by electrostatic and orbital interaction. It has been observed that the absorption spectra of the complex are independent of anion nature but the influence of anion character is observed on frontier molecular orbital pattern. The charge transport property of I-BF4 complex was studied by using tight-binding Hamiltonian approach and found that the hole mobility in I-BF4 is 1.13 × 10-4 cm2 V-1 s-1.

Understanding self-assembly of charged-neutral block copolymer (BCP) and surfactant complexes using molecular dynamics (MD) simulation

NASA Astrophysics Data System (ADS)

Goswami, Monojoy; Sumpter, Bobby; Kilbey, Michael

Here we report the formation of phase separated BCP-surfactant complexes resulting from the electrostatic self-assembly of charge-neutral block copolymers with oppositely charged surfactants. Complexation behaviors of oppositely charged polyelectrolytes has gained considerable attention in the field of soft condensed matter physics due to their potential application as functional nanomaterials for batteries, wastewater treatment and drug delivery systems. Numerous experiments have examined the self-assembled structures resulting from complexation of charge-neutral BCP and surfactants, however, there is a lack of comprehensive understanding at the fundamental level. To help bridge this gap, we use, MD simulations to study self-assembly and dynamics of the BCP-surfactant complex at the molecular level. Our results show an overcharging effect in BCPs with hydrophobic neutral blocks and a formation of core-shell colloidal structure. Hydrophilic neutral blocks, on the other hand, show stable, hairy colloidal structures with neutral blocks forming a loosely-bound, fuzzy outer layer. Our results qualitatively agree with previous SANS and SAXS experiments. This work was supported by the U.S. Department of Energy (DOE), Office of Basic Energy Sciences, Materials Science and Engineering Division.

Structural and motional contributions of the Bacillus subtilis ClpC N-domain in adaptor protein interactions

PubMed Central

Kojetin, Douglas J.; McLaughlin, Patrick D.; Thompson, Richele J.; Dubnau, David; Prepiak, Peter; Rance, Mark; Cavanagh, John

2009-01-01

Summary The AAA+ superfamily protein ClpC is a key regulator of cell development in Bacillus subtilis. As part of a large oligomeric complex, ClpC controls an array of cellular processes by recognizing, unfolding, and providing misfolded and aggregated proteins as substrates for the ClpP peptidase. ClpC is unique compared to other HSP100/Clp proteins, as it requires an adaptor protein for all fundamental activities. The NMR solution structure of the N-terminal repeat domain of ClpC (N-ClpCR) comprises two structural repeats of a four-helix motif. NMR experiments used to map the MecA adaptor protein interaction surface of N-ClpCR reveal that regions involved in the interaction possess conformational flexibility, as well as conformational exchange on the μs-ms time-scale. The electrostatic surface of N-ClpCR differs substantially compared to the N-domain of Escherichia coli ClpA and ClpB, suggesting that the electrostatic surface characteristics of HSP100/Clp N-domains may play a role in adaptor protein and substrate interaction specificity, and perhaps contribute to the unique adaptor protein requirement of ClpC. PMID:19361434

Deciphering the physics and chemistry of perovskites with transmission electron microscopy.

PubMed

Polking, Mark J

2016-03-28

Perovskite oxides exhibit rich structural complexity and a broad range of functional properties, including ferroelectricity, ferromagnetism, and superconductivity. The development of aberration correction for the transmission electron microscope and concurrent progress in electron spectroscopy, electron holography, and other techniques has fueled rapid progress in the understanding of the physics and chemistry of these materials. New techniques based on the transmission electron microscope are first surveyed, and the applications of these techniques for the study of the structure, chemistry, electrostatics, and dynamics of perovskite oxides are then explored in detail, with a particular focus on ferroelectric materials.

A porphyrin complex of Gold(I): (Phosphine)gold(I) azides as cation precursors

PubMed Central

Partyka, David V.; Robilotto, Thomas J.; Zeller, Matthias; Hunter, Allen D.; Gray, Thomas G.

2008-01-01

A silver- and Brönsted acid-free protocol for generating the (tricyclohexylphosphine)gold(I) cation from the corresponding azide complexes is disclosed. The gold(I) cations so liberated are trapped by complexation with octaethylporphyrin. The first structurally authenticated gold(I) porphyrin complex crystallizes with formula C72H112Au2F12N4P2Sb2, space group C2/c, a = 21.388 (4), b = 19.679 (4), c = 19.231 (3) Å; β = 111.030 (3)°. Solution spectroscopic studies indicate that the di-gold complex fragments on dissolution in organic solvents. Approximate density-functional theory calculations find an electrostatic origin for the binding of two gold(I) centers to the unprotonated nitrogen atoms, despite greater orbital density on the porphyrin meso carbons. PMID:18780788

Integration of motor proteins - towards an ATP fueled soft actuator.

PubMed

Kakugo, Akira; Shikinaka, Kazuhiro; Gong, Jian Ping

2008-09-01

We present a soft bio-machine constructed from biological motors (actin/myosin). We have found that chemically cross-linked polymer-actin complex gel filaments can move on myosin coated surfaces with a velocity as high as that of native F-actin, by coupling to ATP hydrolysis. Additionally, it is shown that the velocity of polymer-actin complex gel depends on the species of polycations binding to the F-actins. Since the design of functional actuators of well-defined size and morphology is important, the structural behavior of polymer-actin complexes has been investigated. Our results show that the morphology and growth size of polymer-actin complex can be controlled by changes in the electrostatic interactions between F-actins and polycations. Our results indicate that bio actuators with desired shapes can be created by using a polymer-actin complex.

Electrostatic interaction of positive charges on the surface of Psb31 with photosystem II in the diatom Chaetoceros gracilis.

PubMed

Nagao, Ryo; Suzuki, Takehiro; Okumura, Akinori; Kihira, Tomohiro; Toda, Ayaka; Dohmae, Naoshi; Nakazato, Katsuyoshi; Tomo, Tatsuya

2017-09-01

Psb31, a novel extrinsic protein found in diatom photosystem II (PSII), directly binds to PSII core subunits, independent of the other extrinsic proteins, and functions to maintain optimum oxygen evolution. However, how Psb31 electrostatically interacts with PSII intrinsic proteins remains to be clarified. In this study, we examined electrostatic interaction of Psb31 with PSII complexes isolated from the diatom Chaetoceros gracilis. Positive or negative charges of isolated Psb31 proteins were modified with N-succinimidyl propionate (NSP) or glycine methyl ester (GME), respectively, resulting in formation of uncharged groups. NSP-modified Psb31 did not bind to PSII with a concomitant increase in NSP concentration, whereas GME-modified Psb31 clearly bound to PSII with retention of oxygen-evolving activity, indicating that positive charges of Lys residues and the N-terminus on the surface of Psb31 are involved in electrostatic interactions with PSII intrinsic proteins. Mass spectrometry analysis of NSP-modified Psb31 and sequence comparisons of Psb31 from C. gracilis with other chromophyte algae led to identification of three Lys residues as possible binding sites to PSII. Based on these findings, together with our previous cross-linking study in diatom PSII and a red algal PSII structure, we discuss binding properties of Psb31 with PSII core proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

Prototype electrostatic ground state approach to predicting crystal structures of ionic compounds: Application to hydrogen storage materials

NASA Astrophysics Data System (ADS)

Majzoub, E. H.; Ozoliņš, V.

2008-03-01

We have developed a procedure for crystal structure generation and prediction for ionic compounds consisting of a collection of cations and rigid complex anions. Our approach is based on global optimization of an energy functional consisting of the electrostatic and soft-sphere repulsive energies using Metropolis Monte Carlo (MMC) simulated annealing in conjunction with smoothing of the potential energy landscape via the distance scaling method. The resulting structures, or prototype electrostatic ground states (PEGS), are subsequently relaxed using first-principles density-functional theory (DFT) calculations to obtain accurate structural parameters and thermodynamic properties. This method is shown to produce the ground state structures of NaAlH4 and Mg(AlH4)2 , as well as the mixed cation alanate K2LiAlH6 . For LiAlH4 , the PEGS search produces a structure with a static DFT total energy equal to that of the experimentally observed structure; the latter is stabilized by vibrational contributions to the free energy. For mixed-valence hexa-alanates, XY AlH6 , where X=(Li,Na,K) , and Y=(Mg,Ca) , the PEGS method predicts six unsuspected structure types, which are not found in the existing structure databases. The PEGS search yields energies that are, on the average, better than the best database structures with the same number of atoms per unit cell, demonstrating the predictive power and usefulness of the PEGS structures. In addition to the recently synthesized LiMgAlH6 compound, we predict that LiCaAlH6 , NaCaAlH6 , and KCaAlH6 are also thermodynamically stable with respect to phase separation into other alanates and metal hydrides. In contrast, NaMgAlH6 and KMgAlH6 are slightly unstable (by less than 3kJ/mol ) relative to the phase separation into NaAlH4 , KAlH4 , and MgH2 . We suggest that solid-state ion-exchange reactions between X3AlH6 (X=Li,Na,K) and YCl2 (Y=Mg,Ca) could be used to synthesize the predicted mixed-valence hexa-alanates.

Electrostatic contribution to twist rigidity of DNA.

PubMed

Mohammad-Rafiee, Farshid; Golestanian, Ramin

2004-06-01

The electrostatic contribution to the twist rigidity of DNA is studied, and it is shown that the Coulomb self-energy of the double-helical sugar-phosphate backbone makes a considerable contribution-the electrostatic twist rigidity of DNA is found to be C(elec) approximately 5 nm, which makes up about 7% of its total twist rigidity ( C(DNA) approximately 75 nm). The electrostatic twist rigidity is found, however, to depend only weakly on the salt concentration, because of a competition between two different screening mechanisms: (1) Debye screening by the salt ions in the bulk, and (2) structural screening by the periodic charge distribution along the backbone of the helical polyelectrolyte. It is found that, depending on the parameters, the electrostatic contribution to the twist rigidity could stabilize or destabilize the structure of a helical polyelectrolyte.

Cadmium (II) macrocyclic Schiff-base complexes containing piperazine moiety: Synthesis, spectroscopic, X-ray structure, theoretical and antibacterial studies

NASA Astrophysics Data System (ADS)

Keypour, Hassan; Mahmoudabadi, Masoumeh; Shooshtari, Amir; Bayat, Mehdi; Mohsenzadeh, Fariba; Gable, Robert William

2018-03-01

The new Cd(II) macrocyclic Schiff-base complexes were prepared via the metal templated [1 + 1] cyclocondensation of 2,2'-(piperazine-1,4-diylbis (methylene))dianiline (A) and 2,6-pyridinedicarbaldehyde or 2,6-diacetylpyridine. The products were characterized by elemental analysis, mass spectrometry and spectroscopic methods such as: FT-IR, 1H and 13C-NMR, the crystal structure of [CdL1(ClO4)2](CH3CN) (1) complex was also obtained by single-crystal X-ray crystallography. The complexes were tested for in vitro antibacterial properties against some bacteria. The complexes had antibacterial properties and in some cases were active even more than standards. The geometries of the [CdLn (ClO4)2], (n = 1,2) complexes have been optimized at the BP86/def2-SVP level of theory. Also the nature of Cd←Ln (n = 1, 2) bonds in [CdLn (ClO4)2], (n = 1,2) complexes are studied with the help of NBO and Energy decomposition analysis (EDA). Results showed that the nature of metal-ligand bond in the complexes is slightly more electrostatic with a contribution of about 52% in total interaction energy.

DNA packaging in viral capsids with peptide arms.

PubMed

Cao, Qianqian; Bachmann, Michael

2017-01-18

Strong chain rigidity and electrostatic self-repulsion of packed double-stranded DNA in viruses require a molecular motor to pull the DNA into the capsid. However, what is the role of electrostatic interactions between different charged components in the packaging process? Though various theories and computer simulation models were developed for the understanding of viral assembly and packaging dynamics of the genome, long-range electrostatic interactions and capsid structure have typically been neglected or oversimplified. By means of molecular dynamics simulations, we explore the effects of electrostatic interactions on the packaging dynamics of DNA based on a coarse-grained DNA and capsid model by explicitly including peptide arms (PAs), linked to the inner surface of the capsid, and counterions. Our results indicate that the electrostatic interactions between PAs, DNA, and counterions have a significant influence on the packaging dynamics. We also find that the packed DNA conformations are largely affected by the structure of the PA layer, but the packaging rate is insensitive to the layer structure.

Synthesis, characterization of Ag(I), Pd(II) and Pt(II) complexes of a triazine-3-thione and their interactions with bovine serum albumin

NASA Astrophysics Data System (ADS)

Zhang, Xiuying; Li, Shuyan; Yang, Lin; Fan, Changqing

2007-11-01

Ag(I), Pd(II) and Pt(II) complexes of 5-methoxy-5,6-diphenyl-4,5-dihydro-2H-[1,2,4]triazine-3-thione (LH 2OCH 3) have been synthesized and characterized by elemental analysis, molar conductance, 1H NMR, IR spectra, UV spectra and thermal analysis (TG-DTA). The components of the three complexes are [Ag(C 15H 10N 3S)] 6, Pd(C 15H 10N 3S) 2 and Pt(C 15H 10N 3S) 2·C 3H 6O·2H 2O, respectively. All the complexes are nonelectrolyte and have high thermodynamic stability. The ligand may act as bidentate NS donor for Pd(II) and Pt(II) complexes, while it seems to be bidentate NS bridging via sulphur atom for Ag(I) complex. A planar quadrangular structure is proposed for Pd(II) and Pt(II) complexes and Ag(I) complex may be a hexanuclear cluster. Their interactions with bovine serum albumin (BSA) are investigated using steady state fluorescence technology. It is observed that all of them can quench the intrinsic fluorescence of BSA through static quenching procedure. The binding constants ( KA) at different temperatures, thermodynamic parameters enthalpy changes (Δ H) and entropy changes (Δ S) between BSA and the compounds are calculated. Based on the values of Δ H and Δ S, it is judged that the main acting force of PtL 2·C 3H 6O·2H 2O with BSA may be electrostatic interaction, and for the LH 2OCH 3, Ag 6L 6 and PdL 2, hydrophobic and electrostatic interactions may be involved in their binding processes.

Application of Ring-Closing Metathesis to Grb2 SH3 Domain-Binding Peptides | Center for Cancer Research

Cancer.gov

In silico-generated hypothetical interactions of a ring-closing metathesis-macrocylized peptide bound to the amino terminal SH3 domain of the growth factor receptor bound protein 2 (Grb2). The complex was derived from the NMR solution structure of the bound parent peptide, Ac-V-P-P-P-V-P-P-R-R-R-amide (Protein Data Bank: 3GBQ). The protein surface is shown as electrostatic

Electrostatic interactions play an essential role in the binding of oleic acid with α-lactalbumin in the HAMLET-like complex: a study using charge-specific chemical modifications.

PubMed

Xie, Yongjing; Min, Soyoung; Harte, Níal P; Kirk, Hannah; O'Brien, John E; Voorheis, H Paul; Svanborg, Catharina; Hun Mok, K

2013-01-01

Human α-lactalbumin made lethal to tumor cells (HAMLET) and its analogs are partially unfolded protein-oleic acid (OA) complexes that exhibit selective tumoricidal activity normally absent in the native protein itself. To understand the nature of the interaction between protein and OA moieties, charge-specific chemical modifications of lysine side chains involving citraconylation, acetylation, and guanidination were employed and the biophysical and biological properties were probed. Upon converting the original positively-charged lysine residues to negatively-charged citraconyl or neutral acetyl groups, the binding of OA to protein was eliminated, as were any cytotoxic activities towards osteosarcoma cells. Retention of the positive charges by converting lysine residues to homoarginine groups (guanidination); however, yielded unchanged binding of OA to protein and identical tumoricidal activity to that displayed by the wild-type α-lactalbumin-oleic acid complex. With the addition of OA, the wild-type and guanidinated α-lactalbumin proteins underwent substantial conformational changes, such as partial unfolding, loss of tertiary structure, but retention of secondary structure. In contrast, no significant conformational changes were observed in the citraconylated and acetylated α-lactalbumins, most likely because of the absence of OA binding. These results suggest that electrostatic interactions between the positively-charged basic groups on α-lactalbumin and the negatively-charged carboxylate groups on OA molecules play an essential role in the binding of OA to α-lactalbumin and that these interactions appear to be as important as hydrophobic interactions. Copyright © 2012 Wiley Periodicals, Inc.

Electrostatic Steering Accelerates C3d:CR2 Association

PubMed Central

2016-01-01

Electrostatic effects are ubiquitous in protein interactions and are found to be pervasive in the complement system as well. The interaction between complement fragment C3d and complement receptor 2 (CR2) has evolved to become a link between innate and adaptive immunity. Electrostatic interactions have been suggested to be the driving factor for the association of the C3d:CR2 complex. In this study, we investigate the effects of ionic strength and mutagenesis on the association of C3d:CR2 through Brownian dynamics simulations. We demonstrate that the formation of the C3d:CR2 complex is ionic strength-dependent, suggesting the presence of long-range electrostatic steering that accelerates the complex formation. Electrostatic steering occurs through the interaction of an acidic surface patch in C3d and the positively charged CR2 and is supported by the effects of mutations within the acidic patch of C3d that slow or diminish association. Our data are in agreement with previous experimental mutagenesis and binding studies and computational studies. Although the C3d acidic patch may be locally destabilizing because of unfavorable Coulombic interactions of like charges, it contributes to the acceleration of association. Therefore, acceleration of function through electrostatic steering takes precedence to stability. The site of interaction between C3d and CR2 has been the target for delivery of CR2-bound nanoparticle, antibody, and small molecule biomarkers, as well as potential therapeutics. A detailed knowledge of the physicochemical basis of C3d:CR2 association may be necessary to accelerate biomarker and drug discovery efforts. PMID:27092816

The Electromechanical Behavior of a Micro-Ring Driven by Traveling Electrostatic Force

PubMed Central

Ye, Xiuqian; Chen, Yibao; Chen, Da-Chih; Huang, Kuo-Yi; Hu, Yuh-Chung

2012-01-01

There is no literature mentioning the electromechanical behavior of micro structures driven by traveling electrostatic forces. This article is thus the first to present the dynamics and stabilities of a micro-ring subjected to a traveling electrostatic force. The traveling electrostatic force may be induced by sequentially actuated electrodes which are arranged around the flexible micro-ring. The analysis is based on a linearized distributed model considering the electromechanical coupling effects between electrostatic force and structure. The micro-ring will resonate when the traveling speeds of the electrostatic force approach some critical speeds. The critical speeds are equal to the ratio of the natural frequencies to the wave number of the correlative natural mode of the ring. Apart from resonance, the ring may be unstable at some unstable traveling speeds. The unstable regions appear not only near the critical speeds, but also near some fractions of some critical speeds differences. Furthermore the unstable regions expand with increasing driving voltage. This article may lead to a new research branch on electrostatic-driven micro devices. PMID:22438705

Supramolecular Assembly of Comb-like Macromolecules Induced by Chemical Reactions that Modulate the Macromolecular Interactions In Situ.

PubMed

Xia, Hongwei; Fu, Hailin; Zhang, Yanfeng; Shih, Kuo-Chih; Ren, Yuan; Anuganti, Murali; Nieh, Mu-Ping; Cheng, Jianjun; Lin, Yao

2017-08-16

Supramolecular polymerization or assembly of proteins or large macromolecular units by a homogeneous nucleation mechanism can be quite slow and require specific solution conditions. In nature, protein assembly is often regulated by molecules that modulate the electrostatic interactions of the protein subunits for various association strengths. The key to this regulation is the coupling of the assembly process with a reversible or irreversible chemical reaction that occurs within the constituent subunits. However, realizing this complex process by the rational design of synthetic molecules or macromolecules remains a challenge. Herein, we use a synthetic polypeptide-grafted comb macromolecule to demonstrate how the in situ modulation of interactions between the charged macromolecules affects their resulting supramolecular structures. The kinetics of structural formation was studied and can be described by a generalized model of nucleated polymerization containing secondary pathways. Basic thermodynamic analysis indicated the delicate role of the electrostatic interactions between the charged subunits in the reaction-induced assembly process. This approach may be applicable for assembling a variety of ionic soft matters that are amenable to chemical reactions in situ.

Cartilage-like electrostatic stiffening of responsive cryogel scaffolds

NASA Astrophysics Data System (ADS)

Offeddu, G. S.; Mela, I.; Jeggle, P.; Henderson, R. M.; Smoukov, S. K.; Oyen, M. L.

2017-02-01

Cartilage is a structural tissue with unique mechanical properties deriving from its electrically-charged porous structure. Traditional three-dimensional environments for the culture of cells fail to display the complex physical response displayed by the natural tissue. In this work, the reproduction of the charged environment found in cartilage is achieved using polyelectrolyte hydrogels based on polyvinyl alcohol and polyacrylic acid. The mechanical response and morphology of microporous physically-crosslinked cryogels are compared to those of heat-treated chemical gels made from the same polymers, as a result of pH-dependent swelling. In contrast to the heat-treated chemically-crosslinked gels, the elastic modulus of the physical cryogels was found to increase with charge activation and swelling, explained by the occurrence of electrostatic stiffening of the polymer chains at large charge densities. At the same time, the permeability of both materials to fluid flow was impaired by the presence of electric charges. This cartilage-like mechanical behavior displayed by responsive cryogels can be reproduced in other polyelectrolyte hydrogel systems to fabricate biomimetic cellular scaffolds for the repair of the tissue.

Prediction of Protein-Protein Interaction Sites Using Electrostatic Desolvation Profiles

PubMed Central

Fiorucci, Sébastien; Zacharias, Martin

2010-01-01

Abstract Protein-protein complex formation involves removal of water from the interface region. Surface regions with a small free energy penalty for water removal or desolvation may correspond to preferred interaction sites. A method to calculate the electrostatic free energy of placing a neutral low-dielectric probe at various protein surface positions has been designed and applied to characterize putative interaction sites. Based on solutions of the finite-difference Poisson equation, this method also includes long-range electrostatic contributions and the protein solvent boundary shape in contrast to accessible-surface-area-based solvation energies. Calculations on a large set of proteins indicate that in many cases (>90%), the known binding site overlaps with one of the six regions of lowest electrostatic desolvation penalty (overlap with the lowest desolvation region for 48% of proteins). Since the onset of electrostatic desolvation occurs even before direct protein-protein contact formation, it may help guide proteins toward the binding region in the final stage of complex formation. It is interesting that the probe desolvation properties associated with residue types were found to depend to some degree on whether the residue was outside of or part of a binding site. The probe desolvation penalty was on average smaller if the residue was part of a binding site compared to other surface locations. Applications to several antigen-antibody complexes demonstrated that the approach might be useful not only to predict protein interaction sites in general but to map potential antigenic epitopes on protein surfaces. PMID:20441756

Three-dimensional structural modelling and calculation of electrostatic potentials of HLA Bw4 and Bw6 epitopes to explain the molecular basis for alloantibody binding: toward predicting HLA antigenicity and immunogenicity.

PubMed

Mallon, Dermot H; Bradley, J Andrew; Winn, Peter J; Taylor, Craig J; Kosmoliaptsis, Vasilis

2015-02-01

We have previously shown that qualitative assessment of surface electrostatic potential of HLA class I molecules helps explain serological patterns of alloantibody binding. We have now used a novel computational approach to quantitate differences in surface electrostatic potential of HLA B-cell epitopes and applied this to explain HLA Bw4 and Bw6 antigenicity. Protein structure models of HLA class I alleles expressing either the Bw4 or Bw6 epitope (defined by sequence motifs at positions 77 to 83) were generated using comparative structure prediction. The electrostatic potential in 3-dimensional space encompassing the Bw4/Bw6 epitope was computed by solving the Poisson-Boltzmann equation and quantitatively compared in a pairwise, all-versus-all fashion to produce distance matrices that cluster epitopes with similar electrostatics properties. Quantitative comparison of surface electrostatic potential at the carboxyl terminal of the α1-helix of HLA class I alleles, corresponding to amino acid sequence motif 77 to 83, produced clustering of HLA molecules in 3 principal groups according to Bw4 or Bw6 epitope expression. Remarkably, quantitative differences in electrostatic potential reflected known patterns of serological reactivity better than Bw4/Bw6 amino acid sequence motifs. Quantitative assessment of epitope electrostatic potential allowed the impact of known amino acid substitutions (HLA-B*07:02 R79G, R82L, G83R) that are critical for antibody binding to be predicted. We describe a novel approach for quantitating differences in HLA B-cell epitope electrostatic potential. Proof of principle is provided that this approach enables better assessment of HLA epitope antigenicity than amino acid sequence data alone, and it may allow prediction of HLA immunogenicity.

On the Proper Calculation of Electrostatic Interactions in Solid-Supported Bilayer Systems

DTIC Science & Technology

2011-01-01

the effects of im- plementing different electrostatic boundary conditions on the structural and electrostatic properties of a quartz/water/vacuum...interface and a similar quartz-supported hydrated lipid bilayer exposed to vacuum. Since these interfacial systems have a net polarization, implementing the...implemented electrostatic boundary condition removed these inconsistencies. This formulation is generally applicable to similar interfacial systems in bulk

Continuous development of schemes for parallel computing of the electrostatics in biological systems: implementation in DelPhi.

PubMed

Li, Chuan; Petukh, Marharyta; Li, Lin; Alexov, Emil

2013-08-15

Due to the enormous importance of electrostatics in molecular biology, calculating the electrostatic potential and corresponding energies has become a standard computational approach for the study of biomolecules and nano-objects immersed in water and salt phase or other media. However, the electrostatics of large macromolecules and macromolecular complexes, including nano-objects, may not be obtainable via explicit methods and even the standard continuum electrostatics methods may not be applicable due to high computational time and memory requirements. Here, we report further development of the parallelization scheme reported in our previous work (Li, et al., J. Comput. Chem. 2012, 33, 1960) to include parallelization of the molecular surface and energy calculations components of the algorithm. The parallelization scheme utilizes different approaches such as space domain parallelization, algorithmic parallelization, multithreading, and task scheduling, depending on the quantity being calculated. This allows for efficient use of the computing resources of the corresponding computer cluster. The parallelization scheme is implemented in the popular software DelPhi and results in speedup of several folds. As a demonstration of the efficiency and capability of this methodology, the electrostatic potential, and electric field distributions are calculated for the bovine mitochondrial supercomplex illustrating their complex topology, which cannot be obtained by modeling the supercomplex components alone. Copyright © 2013 Wiley Periodicals, Inc.

A theoretical investigation into the strength of N-NO2 bonds, ring strain and electrostatic potential upon formation of intermolecular H-bonds between HF and the nitro group in nitrogen heterocyclic rings C n H2n N-NO2 (n = 2-5), RDX and HMX.

PubMed

Wang, Bao-Guo; Ren, Fu-de; Shi, Wen-Jing

2015-11-01

Changes in N-NO2 bond strength, ring strain energy and electrostatic potential upon formation of intermolecular H-bonds between HF and the nitro group in nitrogen heterocyclic rings C n H2n N-NO2 (n = 2-5), RDX and HMX were investigated using DFT-B3LYP and MP2(full) methods with the 6-311++G(2df,2p) and aug-cc-pVTZ basis sets. Analysis of electron density shifts was also carried out. The results indicate that H-bonding energy correlates well with the increment of ring strain energy. Upon complex formation, the strength of the N-NO2 trigger-bond is enhanced, suggesting reduced sensitivity, while judged by the increased ring strain energy, sensitivity is increased. However, some features of the molecular surface electrostatic potential, such as a local maximum above the N-NO2 bond and ring, σ + (2) and electrostatic balance parameter ν, remain essentially unchanged upon complex formation, and only a small change in the impact sensitivity h 50 is suggested. It is not sufficient to determine sensitivity solely on the basis of trigger bond or ring strain; as a global feature of a molecule, the molecular surface electrostatic potential is available to help judge the change of sensitivity in H-bonded complexes. Graphical Abstract The strengthened N-NO2 bond suggests reduced sensitivity, while it is reverse by theincreased ring strain energy upon the complex formation. However, the molecular surfaceelectrostatic potential (V S) shows the little change of h 50. The V S should be taken into accountin the analysis of explosive sensitivity in the H-bonded complex.

Edutainment Science: Electrostatics

ERIC Educational Resources Information Center

Ahlers, Carl

2009-01-01

Electrostatics should find a special place in all primary school science curricula. It is a great learning area that reinforces the basics that underpin electricity and atomic structure. Furthermore, it has many well documented hands-on activities. Unfortunately, the "traditional" electrostatics equipment such as PVC rods, woollen cloths, rabbit…

Nonpolar Solvation Free Energy from Proximal Distribution Functions

PubMed Central

Ou, Shu-Ching; Drake, Justin A.; Pettitt, B. Montgomery

2017-01-01

Using precomputed near neighbor or proximal distribution functions (pDFs) that approximate solvent density about atoms in a chemically bonded context one can estimate the solvation structures around complex solutes and the corresponding solute–solvent energetics. In this contribution, we extend this technique to calculate the solvation free energies (ΔG) of a variety of solutes. In particular we use pDFs computed for small peptide molecules to estimate ΔG for larger peptide systems. We separately compute the non polar (ΔGvdW) and electrostatic (ΔGelec) components of the underlying potential model. Here we show how the former can be estimated by thermodynamic integration using pDF-reconstructed solute–solvent interaction energy. The electrostatic component can be approximated with Linear Response theory as half of the electrostatic solute–solvent interaction energy. We test the method by calculating the solvation free energies of butane, propanol, polyalanine, and polyglycine and by comparing with traditional free energy simulations. Results indicate that the pDF-reconstruction algorithm approximately reproduces ΔGvdW calculated by benchmark free energy simulations to within ~ kcal/mol accuracy. The use of transferable pDFs for each solute atom allows for a rapid estimation of ΔG for arbitrary molecular systems. PMID:27992228

Influence of strain relaxation in axial {{In}}_{x}{{Ga}}_{1-x}{\\rm{N}}/{GaN} nanowire heterostructures on their electronic properties

NASA Astrophysics Data System (ADS)

Marquardt, Oliver; Krause, Thilo; Kaganer, Vladimir; Martín-Sánchez, Javier; Hanke, Michael; Brandt, Oliver

2017-05-01

We present a systematic theoretical study of the influence of elastic strain relaxation on the built-in electrostatic potentials and the electronic properties of axial {{In}}x{{Ga}}1-x{{N}}/{GaN} nanowire (NW) heterostructures. Our simulations reveal that for a sufficiently large ratio between the thickness of the {{In}}x{{Ga}}1-x{{N}} disk and the diameter of the NW, the elastic relaxation leads to a significant reduction of the built-in electrostatic potential in comparison to a planar system of similar layer thickness and In content. In this case, the ground state transition energies approach constant values with increasing thickness of the disk and only depend on the In content, a behavior usually associated to that of a quantum well free of built-in electrostatic potentials. We show that the structures under consideration are by no means field-free, and the built-in potentials continue to play an important role even for ultrathin NWs. In particular, strain and the resulting polarization potentials induce complex confinement features of electrons and holes, which depend on the In content, shape, and dimensions of the heterostructure.

A generalized Poisson and Poisson-Boltzmann solver for electrostatic environments.

PubMed

Fisicaro, G; Genovese, L; Andreussi, O; Marzari, N; Goedecker, S

2016-01-07

The computational study of chemical reactions in complex, wet environments is critical for applications in many fields. It is often essential to study chemical reactions in the presence of applied electrochemical potentials, taking into account the non-trivial electrostatic screening coming from the solvent and the electrolytes. As a consequence, the electrostatic potential has to be found by solving the generalized Poisson and the Poisson-Boltzmann equations for neutral and ionic solutions, respectively. In the present work, solvers for both problems have been developed. A preconditioned conjugate gradient method has been implemented for the solution of the generalized Poisson equation and the linear regime of the Poisson-Boltzmann, allowing to solve iteratively the minimization problem with some ten iterations of the ordinary Poisson equation solver. In addition, a self-consistent procedure enables us to solve the non-linear Poisson-Boltzmann problem. Both solvers exhibit very high accuracy and parallel efficiency and allow for the treatment of periodic, free, and slab boundary conditions. The solver has been integrated into the BigDFT and Quantum-ESPRESSO electronic-structure packages and will be released as an independent program, suitable for integration in other codes.

A generalized Poisson and Poisson-Boltzmann solver for electrostatic environments

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

Fisicaro, G., E-mail: giuseppe.fisicaro@unibas.ch; Goedecker, S.; Genovese, L.

2016-01-07

The computational study of chemical reactions in complex, wet environments is critical for applications in many fields. It is often essential to study chemical reactions in the presence of applied electrochemical potentials, taking into account the non-trivial electrostatic screening coming from the solvent and the electrolytes. As a consequence, the electrostatic potential has to be found by solving the generalized Poisson and the Poisson-Boltzmann equations for neutral and ionic solutions, respectively. In the present work, solvers for both problems have been developed. A preconditioned conjugate gradient method has been implemented for the solution of the generalized Poisson equation and themore » linear regime of the Poisson-Boltzmann, allowing to solve iteratively the minimization problem with some ten iterations of the ordinary Poisson equation solver. In addition, a self-consistent procedure enables us to solve the non-linear Poisson-Boltzmann problem. Both solvers exhibit very high accuracy and parallel efficiency and allow for the treatment of periodic, free, and slab boundary conditions. The solver has been integrated into the BigDFT and Quantum-ESPRESSO electronic-structure packages and will be released as an independent program, suitable for integration in other codes.« less

Prediction of enzyme binding: human thrombin inhibition study by quantum chemical and artificial intelligence methods based on X-ray structures.

PubMed

Mlinsek, G; Novic, M; Hodoscek, M; Solmajer, T

2001-01-01

Thrombin is a serine protease which plays important roles in the human body, the key one being the control of thrombus formation. The inhibition of thrombin has become a target for new antithrombotics. The aim of our work was to (i) construct a model which would enable us to predict Ki values for the binding of an inhibitor into the active site of thrombin based on a database of known X-ray structures of inhibitor-enzyme complexes and (ii) to identify the structural and electrostatic characteristics of inhibitor molecules crucially important to their effective binding. To retain as much of the 3D structural information of the bound inhibitor as possible, we implemented the quantum mechanical/molecular mechanical (QM/MM) procedure for calculating the molecular electrostatic potential (MEP) at the van der Waals surfaces of atoms in the protein's active site. The inhibitor was treated quantum mechanically, while the rest of the complex was treated by classical means. The obtained MEP values served as inputs into the counter-propagation artificial neural network (CP-ANN), and a genetic algorithm was subsequently used to search for the combination of atoms that predominantly influences the binding. The constructed CP-ANN model yielded Ki values predictions with a correlation coefficient of 0.96, with Ki values extended over 7 orders of magnitude. Our approach also shows the relative importance of the various amino acid residues present in the active site of the enzyme for inhibitor binding. The list of residues selected by our automatic procedure is in good correlation with the current consensus regarding the importance of certain crucial residues in thrombin's active site.

Structure-based affinity maturation of a chimeric anti-ricin antibody C4C13.

PubMed

Luo, Longlong; Luo, Qun; Guo, Leiming; Lv, Ming; Lin, Zhou; Geng, Jing; Li, Xinying; Li, Yan; Shen, Beifen; Qiao, Chunxia; Feng, Jiannan

2014-01-01

Ricin is a highly lethal toxin. Anti-ricin chimeric monoclonal antibody (mAb) C4C13 was prepared in our lab; however, its binding affinity was much weaker than that of the parent antibody 4C13. In this study, based on the computer-guided homology modeling and conformational optimization methods, the 3-D structure of C4C13 variable regions Fv was constructed and optimized. Using molecular docking and dynamics simulation methods, the 3-D complex structure of ricin and C4C13 Fv was obtained. Considering the orientation property, surface electrostatic distribution, residues chemical and physical character and intermolecular hydrogen bond, the binding mode and key residues were predicted. According to C4C13 Fv fragment and ricin complementary binding surface, electrostatic attraction periphery and van der Waals interaction interface, three mutants (i.e., M1 (N(H102)F, W(H103)Y); M2 (W(H103)Y) and M3 (R(L90)G)) were designed, in which M1 and M2 were predicted to possess higher antigen-binding activity than C4C13, while M3 was weaker. The relative affinity assays by ELISA showed that M1 and M2 mutations had higher affinity (9.6 and 18.3 nmol/L) than C4C13 (130 nmol/L) and M3 had weaker affinity (234.5 nmol/L) than C4C13. The results showed that the modeling complex structure of the antigen (ricin) and antibody (C4C13) is reasonable. Our work offered affinity maturated antibodies by site mutations, which were beneficial for valuable anti-ricin antibody design and preparation in future.

Self-Assembly of Porphyrin J-Aggregates

NASA Astrophysics Data System (ADS)

Snitka, Valentinas; Rackaitis, Mindaugas; Navickaite, Gintare

2006-03-01

The porphyrin nanotubes were built by ionic self-assembly of two oppositely charged porphyrins in aqueous solution. The porphyrins in the acid aqueous solution self-assemble into J-aggregates, wheels or other structures. The electrostatic forces between these porphyrin blocks contribute to the formation of porphyrin aggregates in the form of nanotubes, enhance the structural stability of these nanostructures. The nanotubes were composed mixing aqueous solutions of the two porphyrins - anionic Meso-tetra(4- sulfonatophrnyl)porhine dihydrochloride (TPPS4) and cationic Meso-tetra(4-pyridyl)porphine (T4MPyP). The porphyrin nanotubes obtained are hollow structures with the length of 300 nm and diameter 50 nm. Photocatalytic porphyrins are used to reduce metal complexes from aqueous solution and to control the deposition of Au from AuHCl4 and Au nanoparticles colloid solutions onto porphyrin nanotubes. Porphyrin nanotubes are shown to reduce metal complexes and deposit the metal selectively onto the inner or outer surface of the tubes, leading to nanotube-metal composite structures.

FINITE EXPANSION METHOD FOR THE CALCULATION AND INTERPRETATION OF MOLECULAR ELECTROSTATIC POTENTIALS

EPA Science Inventory

Because it is useful to have the molecular electrostatic potential as an element in a complex scheme to assess the toxicity of large molecules, efficient and reliable methods are needed for the calculation and characterization of these potentials. A multicenter multipole expansio...

Theoretical study of mixed MLaX(4) (M = Na, K, Cs; X = F, Cl, Br, I) rare earth/alkali metal halide complexes.

PubMed

Groen, Cornelis Petrus; Oskam, Ad; Kovács, Attila

2003-02-10

The structure, bonding, and vibrational properties of the mixed MLaX(4) (M = Na, K, Cs; X = F, Cl, Br, I) rare earth/alkali metal halide complexes have been studied using the MP2 method in conjunction with polarized triple-zeta valence basis sets and quasi-relativistic effective core potentials for the heavy atoms. From the three characteristic structures, possessing 1- (C(3)(v)), 2- (C(2)(v)), or 3-fold coordination (C(3)(v)) between the alkali metal and the bridging halide atoms, the bi- and tridentate forms are stable isomers with close dissociation energies. In general, for the complexes existing of lighter alkali metals and halogens, the bidentate structure corresponds to the global minimum of the potential energy surface, while the heavier analogues favor the tridentate structure. At experimentally relevant temperatures (T > 800 K), however, the isomerization entropy leads to a domination of the bidentate structures over the tridentate forms for all complexes. An important effect of the size of the alkali metal is manifested in the larger stabilities of the K and Cs complexes. The natural atomic charges are in agreement with strong electrostatic interactions in the title complexes. The marginal covalent contributions show a slight increasing trend in the heavier analogues. The calculated vibrational data indicate that infrared spectroscopy may be an effective tool for experimental investigation and characterization of MLaX(4) molecules.

Energy component analysis of π interactions.

PubMed

Sherrill, C David

2013-04-16

Fundamental features of biomolecules, such as their structure, solvation, and crystal packing and even the docking of drugs, rely on noncovalent interactions. Theory can help elucidate the nature of these interactions, and energy component analysis reveals the contributions from the various intermolecular forces: electrostatics, London dispersion terms, induction (polarization), and short-range exchange-repulsion. Symmetry-adapted perturbation theory (SAPT) provides one method for this type of analysis. In this Account, we show several examples of how SAPT provides insight into the nature of noncovalent π-interactions. In cation-π interactions, the cation strongly polarizes electrons in π-orbitals, leading to substantially attractive induction terms. This polarization is so important that a cation and a benzene attract each other when placed in the same plane, even though a consideration of the electrostatic interactions alone would suggest otherwise. SAPT analysis can also support an understanding of substituent effects in π-π interactions. Trends in face-to-face sandwich benzene dimers cannot be understood solely in terms of electrostatic effects, especially for multiply substituted dimers, but SAPT analysis demonstrates the importance of London dispersion forces. Moreover, detailed SAPT studies also reveal the critical importance of charge penetration effects in π-stacking interactions. These effects arise in cases with substantial orbital overlap, such as in π-stacking in DNA or in crystal structures of π-conjugated materials. These charge penetration effects lead to attractive electrostatic terms where a simpler analysis based on atom-centered charges, electrostatic potential plots, or even distributed multipole analysis would incorrectly predict repulsive electrostatics. SAPT analysis of sandwich benzene, benzene-pyridine, and pyridine dimers indicates that dipole/induced-dipole terms present in benzene-pyridine but not in benzene dimer are relatively unimportant. In general, a nitrogen heteroatom contracts the electron density, reducing the magnitude of both the London dispersion and the exchange-repulsion terms, but with an overall net increase in attraction. Finally, using recent advances in SAPT algorithms, researchers can now perform SAPT computations on systems with 200 atoms or more. We discuss a recent study of the intercalation complex of proflavine with a trinucleotide duplex of DNA. Here, London dispersion forces are the strongest contributors to binding, as is typical for π-π interactions. However, the electrostatic terms are larger than usual on a fractional basis, which likely results from the positive charge on the intercalator and its location between two electron-rich base pairs. These cation-π interactions also increase the induction term beyond those of typical noncovalent π-interactions.

Structural bioinformatics: methods, concepts and applications to blood coagulation proteins.

PubMed

Villoutreix, Bruno O

2002-06-01

Structural and theoretical analyses of proteins are central to the understanding of complex molecular mechanisms and are fundamental to the drug discovery process. Computational techniques yield useful insights into an ever-wider range of biomolecular systems. Protein three-dimensional structures and molecular functions can be predicted in some circumstances, while experimental structures can be analyzed in depth via such computational approaches. Non-covalent binding of biomolecules can be understood by considering structural, thermodynamic and kinetic issues, and theoretical simulations of such events can be attempted. The central role of electrostatic interactions with regard to protein function, structure and stability has been investigated and some electrostatic properties can be modeled theoretically. Computer methods thus help to prioritize, design, analyze and rationalize biochemical experiments. Cardiovascular diseases and associated blood coagulation disorders are leading causes of death worldwide. Blood coagulation involves more than 30 proteins that interact specifically with various degrees of affinity. Many of these molecules can also bind transiently to phospholipid surfaces. Numerous point mutations in the genes of coagulation proteins and regulators have been identified. Understanding the coagulation cascade, its regulation and the impact of mutations is required for the development of new therapies and diagnostic tools. In this review, we describe concepts and methods pertaining to the field of structural bioinformatics. We provide examples of applications of these approaches to blood coagulation proteins and show that such studies can give insights about molecular mechanisms contributing to cardiovascular disease susceptibility.

Partially Glycosylated Dendrimers Block MD-2 and Prevent TLR4-MD-2-LPS Complex Mediated Cytokine Responses

PubMed Central

Barata, Teresa S.; Teo, Ian; Brocchini, Steve; Zloh, Mire; Shaunak, Sunil

2011-01-01

The crystal structure of the TLR4-MD-2-LPS complex responsible for triggering powerful pro-inflammatory cytokine responses has recently become available. Central to cell surface complex formation is binding of lipopolysaccharide (LPS) to soluble MD-2. We have previously shown, in biologically based experiments, that a generation 3.5 PAMAM dendrimer with 64 peripheral carboxylic acid groups acts as an antagonist of pro-inflammatory cytokine production after surface modification with 8 glucosamine molecules. We have also shown using molecular modelling approaches that this partially glycosylated dendrimer has the flexibility, cluster density, surface electrostatic charge, and hydrophilicity to make it a therapeutically useful antagonist of complex formation. These studies enabled the computational study of the interactions of the unmodified dendrimer, glucosamine, and of the partially glycosylated dendrimer with TLR4 and MD-2 using molecular docking and molecular dynamics techniques. They demonstrate that dendrimer glucosamine forms co-operative electrostatic interactions with residues lining the entrance to MD-2's hydrophobic pocket. Crucially, dendrimer glucosamine interferes with the electrostatic binding of: (i) the 4′phosphate on the di-glucosamine of LPS to Ser118 on MD-2; (ii) LPS to Lys91 on MD-2; (iii) the subsequent binding of TLR4 to Tyr102 on MD-2. This is followed by additional co-operative interactions between several of the dendrimer glucosamine's carboxylic acid branches and MD-2. Collectively, these interactions block the entry of the lipid chains of LPS into MD-2's hydrophobic pocket, and also prevent TLR4-MD-2-LPS complex formation. Our studies have therefore defined the first nonlipid-based synthetic MD-2 antagonist using both animal model-based studies of pro-inflammatory cytokine responses and molecular modelling studies of a whole dendrimer with its target protein. Using this approach, it should now be possible to computationally design additional macromolecular dendrimer based antagonists for other Toll Like Receptors. They could be useful for treating a spectrum of infectious, inflammatory and malignant diseases. PMID:21738462

Study of the extra-ionic electron distributions in semi-metallic structures by nuclear quadrupole resonance techniques

NASA Technical Reports Server (NTRS)

Murty, A. N.

1976-01-01

A straightforward self-consistent method was developed to estimate solid state electrostatic potentials, fields and field gradients in ionic solids. The method is a direct practical application of basic electrostatics to solid state and also helps in the understanding of the principles of crystal structure. The necessary mathematical equations, derived from first principles, were presented and the systematic computational procedure developed to arrive at the solid state electrostatic field gradients values was given.

Structural phylogeny by profile extraction and multiple superimposition using electrostatic congruence as a discriminator

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

Chakraborty, Sandeep; Rao, Basuthkar J.; Baker, Nathan A.

2013-04-01

Phylogenetic analysis of proteins using multiple sequence alignment (MSA) assumes an underlying evolutionary relationship in these proteins which occasionally remains undetected due to considerable sequence divergence. Structural alignment programs have been developed to unravel such fuzzy relationships. However, none of these structure based methods have used electrostatic properties to discriminate between spatially equivalent residues. We present a methodology for MSA of a set of related proteins with known structures using electrostatic properties as an additional discriminator (STEEP). STEEP first extracts a profile, then generates a multiple structural superimposition providing a consolidated spatial framework for comparing residues and finally emits themore » MSA. Residues that are aligned differently by including or excluding electrostatic properties can be targeted by directed evolution experiments to transform the enzymatic properties of one protein into another. We have compared STEEP results to those obtained from a MSA program (ClustalW) and a structural alignment method (MUSTANG) for chymotrypsin serine proteases. Subsequently, we used PhyML to generate phylogenetic trees for the serine and metallo-β-lactamase superfamilies from the STEEP generated MSA, and corroborated the accepted relationships in these superfamilies. We have observed that STEEP acts as a functional classifier when electrostatic congruence is used as a discriminator, and thus identifies potential targets for directed evolution experiments. In summary, STEEP is unique among phylogenetic methods for its ability to use electrostatic congruence to specify mutations that might be the source of the functional divergence in a protein family. Based on our results, we also hypothesize that the active site and its close vicinity contains enough information to infer the correct phylogeny for related proteins.« less

The pKa Cooperative: A Collaborative Effort to Advance Structure-Based Calculations of pKa values and Electrostatic Effects in Proteins

PubMed Central

Nielsen, Jens E.; Gunner, M. R.; Bertrand García-Moreno, E.

2012-01-01

The pKa Cooperative http://www.pkacoop.org was organized to advance development of accurate and useful computational methods for structure-based calculation of pKa values and electrostatic energy in proteins. The Cooperative brings together laboratories with expertise and interest in theoretical, computational and experimental studies of protein electrostatics. To improve structure-based energy calculations it is necessary to better understand the physical character and molecular determinants of electrostatic effects. The Cooperative thus intends to foment experimental research into fundamental aspects of proteins that depend on electrostatic interactions. It will maintain a depository for experimental data useful for critical assessment of methods for structure-based electrostatics calculations. To help guide the development of computational methods the Cooperative will organize blind prediction exercises. As a first step, computational laboratories were invited to reproduce an unpublished set of experimental pKa values of acidic and basic residues introduced in the interior of staphylococcal nuclease by site-directed mutagenesis. The pKa values of these groups are unique and challenging to simulate owing to the large magnitude of their shifts relative to normal pKa values in water. Many computational methods were tested in this 1st Blind Prediction Challenge and critical assessment exercise. A workshop was organized in the Telluride Science Research Center to assess objectively the performance of many computational methods tested on this one extensive dataset. This volume of PROTEINS: Structure, Function, and Bioinformatics introduces the pKa Cooperative, presents reports submitted by participants in the blind prediction challenge, and highlights some of the problems in structure-based calculations identified during this exercise. PMID:22002877

Impact of underlap spacer region variation on electrostatic and analog performance of symmetrical high-k SOI FinFET at 20 nm channel length

NASA Astrophysics Data System (ADS)

Jain, Neeraj; Raj, Balwinder

2017-12-01

Continued scaling of CMOS technology to achieve high performance and low power consumption of semiconductor devices in the complex integrated circuits faces the degradation in terms of electrostatic integrity, short channel effects (SCEs), leakage currents, device variability and reliability etc. Nowadays, multigate structure has become the promising candidate to overcome these problems. SOI FinFET is one of the best multigate structures that has gained importance in all electronic design automation (EDA) industries due to its improved short channel effects (SCEs), because of its more effective gate-controlling capabilities. In this paper, our aim is to explore the sensitivity of underlap spacer region variation on the performance of SOI FinFET at 20 nm channel length. Electric field modulation is analyzed with spacer length variation and electrostatic performance is evaluated in terms of performance parameter like electron mobility, electric field, electric potential, sub-threshold slope (SS), ON current (I on), OFF current (I off) and I on/I off ratio. The potential benefits of SOI FinFET at drain-to-source voltage, V DS = 0.05 V and V DS = 0.7 V towards analog and RF design is also evaluated in terms of intrinsic gain (A V), output conductance (g d), trans-conductance (g m), gate capacitance (C gg), and cut-off frequency (f T = g m/2πC gg) with spacer region variations.

Synthesis and structure elucidation of a copper(II) Schiff-base complex: in vitro DNA binding, pBR322 plasmid cleavage and HSA binding studies.

PubMed

Tabassum, Sartaj; Ahmad, Musheer; Afzal, Mohd; Zaki, Mehvash; Bharadwaj, Parimal K

2014-11-01

New copper(II) complex with Schiff base ligand 4-[(2-Hydroxy-3-methoxy-benzylidene)-amino]-benzoic acid (H₂L) was synthesized and characterized by spectroscopic and analytical and single crystal X-ray diffraction studies which revealed that the complex 1 exist in a distorted octahedral environment. In vitro CT-DNA binding studies were performed by employing different biophysical technique which indicated that the 1 strongly binds to DNA in comparison to ligand via electrostatic binding mode. Complex 1 cleaves pBR322 DNA via hydrolytic pathway and recognizes minor groove of DNA double helix. The HSA binding results showed that ligand and complex 1 has ability to quench the fluorescence emission intensity of Trp 214 residue available in the subdomain IIA of HSA. Copyright © 2014 Elsevier B.V. All rights reserved.

Spatial Distributions of Guest Molecule and Hydration Level in Dendrimer-Based Guest–Host Complex

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

Liu, Chih-Ying; Chen, Hsin-Lung; Do, Changwoo

2016-08-09

Using the electrostatic complex of G4 poly(amidoamine) (PAMAM) dendrimer with an amphiphilic surfactant as a model system, contrast variation small angle neutron scattering (SANS) is implemented to resolve the key structural characteristics of dendrimer-based guest–host system. Quantifications of the radial distributions of the scattering length density and the hydration level within the complex molecule reveal that the surfactant is embedded in the peripheral region of dendrimer and the steric crowding in this region increases the backfolding of the dendritic segments, thereby reducing the hydration level throughout the complex molecule. Here, the insights into the spatial location of the guest moleculesmore » as well as the perturbations of dendrimer conformation and hydration level deduced here are crucial for the delicate design of dendrimer-based guest–host system for biomedical applications.« less

Probing electrostatic interactions and ligand binding in aspartyl-tRNA synthetase through site-directed mutagenesis and computer simulations.

PubMed

Thompson, Damien; Lazennec, Christine; Plateau, Pierre; Simonson, Thomas

2008-05-15

Faithful genetic code translation requires that each aminoacyl-tRNA synthetase recognise its cognate amino acid ligand specifically. Aspartyl-tRNA synthetase (AspRS) distinguishes between its negatively-charged Asp substrate and two competitors, neutral Asn and di-negative succinate, using a complex network of electrostatic interactions. Here, we used molecular dynamics simulations and site-directed mutagenesis experiments to probe these interactions further. We attempt to decrease the Asp/Asn binding free energy difference via single, double and triple mutations that reduce the net positive charge in the active site of Escherichia coli AspRS. Earlier, Glutamine 199 was changed to a negatively-charged glutamate, giving a computed reduction in Asp affinity in good agreement with experiment. Here, Lysine 198 was changed to a neutral leucine; then, Lys198 and Gln199 were mutated simultaneously. Both mutants are predicted to have reduced Asp binding and improved Asn binding, but the changes are insufficient to overcome the initial, high specificity of the native enzyme, which retains a preference for Asp. Probing the aminoacyl-adenylation reaction through pyrophosphate exchange experiments, we found no detectable activity for the mutant enzymes, indicating weaker Asp binding and/or poorer transition state stabilization. The simulations show that the mutations' effect is partly offset by proton uptake by a nearby histidine. Therefore, we performed additional simulations where the nearby Histidines 448 and 449 were mutated to neutral or negative residues: (Lys198Leu, His448Gln, His449Gln), and (Lys198Leu, His448Glu, His449Gln). This led to unexpected conformational changes and loss of active site preorganization, suggesting that the AspRS active site has a limited structural tolerance for electrostatic modifications. The data give insights into the complex electrostatic network in the AspRS active site and illustrate the difficulty in engineering charged-to-neutral changes of the preferred ligand. 2007 Wiley-Liss, Inc.

Extending the Diffuse Layer Model of Surface Acidity Constant Behavior: IV. Diffuse Layer Charge/Potential Relationships

EPA Science Inventory

Most current electrostatic surface complexation models describing ionic binding at the particle/water interface rely on the use of Poisson - Boltzmann (PB) theory for relating diffuse layer charge densities to diffuse layer electrostatic potentials. PB theory is known to contain ...

Surface properties of adipocyte lipid-binding protein: Response to lipid binding, and comparison with homologous proteins.

PubMed

LiCata, V J; Bernlohr, D A

1998-12-01

Adipocyte lipid-binding protein (ALBP) is one of a family of intracellular lipid-binding proteins (iLBPs) that bind fatty acids, retinoids, and other hydrophobic ligands. The different members of this family exhibit a highly conserved three-dimensional structure; and where structures have been determined both with (holo) and without (apo) bound lipid, observed conformational changes are extremely small (Banaszak, et al., 1994, Adv. Prot. Chem. 45, 89; Bernlohr, et al., 1997, Annu. Rev. Nutr. 17, 277). We have examined the electrostatic, hydrophobic, and water accessible surfaces of ALBP in the apo form and of holo forms with a variety of bound ligands. These calculations reveal a number of previously unrecognized changes between apo and holo ALBP, including: 1) an increase in the overall protein surface area when ligand binds, 2) expansion of the binding cavity when ligand is bound, 3) clustering of individual residue exposure increases in the area surrounding the proposed ligand entry portal, and 4) ligand-binding dependent variation in the topology of the electrostatic potential in the area surrounding the ligand entry portal. These focused analyses of the crystallographic structures thus reveal a number of subtle but consistent conformational and surface changes that might serve as markers for differential targeting of protein-lipid complexes within the cell. Most changes are consistent from ligand to ligand, however there are some ligand-specific changes. Comparable calculations with intestinal fatty-acid-binding protein and other vertebrate iLBPs show differences in the electrostatic topology, hydrophobic topology, and in localized changes in solvent exposure near the ligand entry portal. These results provide a basis toward understanding the functional and mechanistic differences among these highly structurally homologous proteins. Further, they suggest that iLBPs from different tissues exhibit one of two predominant end-state structural distributions of the ligand entry portal.

Structural Characterization of a Thrombin-Aptamer Complex by High Resolution Native Top-Down Mass Spectrometry

NASA Astrophysics Data System (ADS)

Zhang, Jiang; Loo, Rachel R. Ogorzalek; Loo, Joseph A.

2017-09-01

Native mass spectrometry (MS) with electrospray ionization (ESI) has evolved as an invaluable tool for the characterization of intact native proteins and non-covalently bound protein complexes. Here we report the structural characterization by high resolution native top-down MS of human thrombin and its complex with the Bock thrombin binding aptamer (TBA), a 15-nucleotide DNA with high specificity and affinity for thrombin. Accurate mass measurements revealed that the predominant form of native human α-thrombin contains a glycosylation mass of 2205 Da, corresponding to a sialylated symmetric biantennary oligosaccharide structure without fucosylation. Native MS showed that thrombin and TBA predominantly form a 1:1 complex under near physiological conditions (pH 6.8, 200 mM NH4OAc), but the binding stoichiometry is influenced by the solution ionic strength. In 20 mM ammonium acetate solution, up to two TBAs were bound to thrombin, whereas increasing the solution ionic strength destabilized the thrombin-TBA complex and 1 M NH4OAc nearly completely dissociated the complex. This observation is consistent with the mediation of thrombin-aptamer binding through electrostatic interactions and it is further consistent with the human thrombin structure that contains two anion binding sites on the surface. Electron capture dissociation (ECD) top-down MS of the thrombin-TBA complex performed with a high resolution 15 Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer showed the primary binding site to be at exosite I located near the N-terminal sequence of the heavy chain, consistent with crystallographic data. High resolution native top-down MS is complementary to traditional structural biology methods for structurally characterizing native proteins and protein-DNA complexes. [Figure not available: see fulltext.

Fluorescence turn-on responses of anionic and cationic conjugated polymers toward proteins: effect of electrostatic and hydrophobic interactions.

PubMed

Pu, Kan-Yi; Liu, Bin

2010-03-11

Cationic and anionic poly(fluorenyleneethynylene-alt-benzothiadiazole)s (PFEBTs) are designed and synthesized via Sonagashira coupling reaction to show light-up signatures toward proteins. Due to the charge transfer character of the excited states, the fluorescence of PFEBTs is very weak in aqueous solution, while their yellow fluorescence can be enhanced by polymer aggregation. PFEBTs show fluorescence turn-on rather than fluorescence quenching upon complexation with proteins. Both electrostatic and hydrophobic interactions between PFEBTs and proteins are found to improve the polymer fluorescence, the extent of which is dependent on the nature of the polymer and the protein. Changes in solution pH adjust the net charges of proteins, providing an effective way to manipulate electrostatic interactions and in turn the increment in the polymer fluorescence. In addition, the effect of protein digestion on the fluorescence of polymer/protein complexes is probed. The results indicate that electrostatic interaction induced polymer fluorescence increase cannot be substantially reduced through cleaving protein into peptide fragments. In contrast, hydrophobic interactions, mainly determined by the hydrophobicity of proteins, can be minimized by digestion, imparting a light-off signature for the polymer/protein complexes. This study thus not only highlights the opportunities of exerting nonspecific interactions for protein sensing but also reveals significant implications for biosensor design.

Effects of dielectric inhomogeneity on electrostatic twist rigidity of a helical biomolecule in Debye-Hückel regime

NASA Astrophysics Data System (ADS)

Rezaie-Dereshgi, Amir; Mohammad-Rafiee, Farshid

2018-04-01

The electrostatic interactions play a crucial role in biological systems. Here we consider an impermeable dielectric molecule in the solvent with a different dielectric constant. The electrostatic free energy in the problem is studied in the Debye-Hückel regime using the analytical Green function that is calculated in the paper. Using this electrostatic free energy, we study the electrostatic contribution to the twist rigidity of a double stranded helical molecule such as a DNA and an actin filament. The dependence of the electrostatic twist rigidity of the molecule to the dielectric inhomogeneity, structural parameters, and the salt concentration is studied. It is shown that, depending on the parameters, the electrostatic twist rigidity could be positive or negative.

Electrostatic Inflation of Membrane Space Structures

NASA Astrophysics Data System (ADS)

Stiles, Laura A.

Membrane space structures provide a lightweight and cost effective alternative to traditional mechanical systems. The low-mass and high deployed-to-stored volume ratios allow for larger structures to be launched, expanding on-orbit science and technology capabilities. This research explores a novel method for deployment of membrane space structures using electrostatic pressure as the inflation mechanism. Applying electric charge to a layered gossamer structure provides an inflationary pressure due to the repulsive electrostatic forces between the charged layers. The electrostatic inflation of membrane structures (EIMS) concept is particularly applicable to non-precision structures such as sunshields or drag de-orbiting devices. This research addresses three fundamental topics: necessary conditions for EIMS in a vacuum, necessary conditions for EIMS in a plasma, and charging methods. Vacuum demonstrations show that less than 10 kiloVolts are required for electrostatic inflation of membrane structures in 1-g. On-orbit perturbation forces can be much smaller, suggesting feasible voltage requirements. Numerical simulation enables a relationship between required inflation pressure (to offset disturbances) and voltage. 100's of Volts are required for inflation in geosynchronous orbits (GEO) and a few kiloVolts in low Earth orbit (LEO). While GEO plasma has a small impact on the EIMS performance, Debye shielding at LEO reduces the electrostatic pressure. The classic Debye shielding prediction is far worse than actual shielding, raising the `effective' Debye length to the meter scale in LEO, suggesting feasibility for EIMS in LEO. Charged particle emission and remote charging methods are explored as inflation mechanisms. Secondary electron emission characteristics of EIMS materials were determined experimentally. Nonlinear fits to the Sternglass curve determined a maximum yield of 1.83 at 433 eV for Aluminized Kapton and a maximum yield of 1.78 at 511 eV for Aluminized Mylar. Remote charging was demonstrated to -500 V with a 5 keV electron beam. Charge emission power levels are below 1 Watt in GEO and from 10's of Watt to a kiloWatt in LEO.

An ionic-chemical-mechanical model for muscle contraction.

PubMed

Manning, Gerald S

2016-12-01

The dynamic process underlying muscle contraction is the parallel sliding of thin actin filaments along an immobile thick myosin fiber powered by oar-like movements of protruding myosin cross bridges (myosin heads). The free energy for functioning of the myosin nanomotor comes from the hydrolysis of ATP bound to the myosin heads. The unit step of translational movement is based on a mechanical-chemical cycle involving ATP binding to myosin, hydrolysis of the bound ATP with ultimate release of the hydrolysis products, stress-generating conformational changes in the myosin cross bridge, and relief of built-up stress in the myosin power stroke. The cycle is regulated by a transition between weak and strong actin-myosin binding affinities. The dissociation of the weakly bound complex by addition of salt indicates the electrostatic basis for the weak affinity, while structural studies demonstrate that electrostatic interactions among negatively charged amino acid residues of actin and positively charged residues of myosin are involved in the strong binding interface. We therefore conjecture that intermediate states of increasing actin-myosin engagement during the weak-to-strong binding transition also involve electrostatic interactions. Methods of polymer solution physics have shown that the thin actin filament can be regarded in some of its aspects as a net negatively charged polyelectrolyte. Here we employ polyelectrolyte theory to suggest how actin-myosin electrostatic interactions might be of significance in the intermediate stages of binding, ensuring an engaged power stroke of the myosin motor that transmits force to the actin filament, and preventing the motor from getting stuck in a metastable pre-power stroke state. We provide electrostatic force estimates that are in the pN range known to operate in the cycle. © 2016 Wiley Periodicals, Inc.

Structural Dynamics Investigation of Human Family 1 & 2 Cystatin-Cathepsin L1 Interaction: A Comparison of Binding Modes

PubMed Central

Nandy, Suman Kumar; Seal, Alpana

2016-01-01

Cystatin superfamily is a large group of evolutionarily related proteins involved in numerous physiological activities through their inhibitory activity towards cysteine proteases. Despite sharing the same cystatin fold, and inhibiting cysteine proteases through the same tripartite edge involving highly conserved N-terminal region, L1 and L2 loop; cystatins differ widely in their inhibitory affinity towards C1 family of cysteine proteases and molecular details of these interactions are still elusive. In this study, inhibitory interactions of human family 1 & 2 cystatins with cathepsin L1 are predicted and their stability and viability are verified through protein docking & comparative molecular dynamics. An overall stabilization effect is observed in all cystatins on complex formation. Complexes are mostly dominated by van der Waals interaction but the relative participation of the conserved regions varied extensively. While van der Waals contacts prevail in L1 and L2 loop, N-terminal segment chiefly acts as electrostatic interaction site. In fact the comparative dynamics study points towards the instrumental role of L1 loop in directing the total interaction profile of the complex either towards electrostatic or van der Waals contacts. The key amino acid residues surfaced via interaction energy, hydrogen bonding and solvent accessible surface area analysis for each cystatin-cathepsin L1 complex influence the mode of binding and thus control the diverse inhibitory affinity of cystatins towards cysteine proteases. PMID:27764212

On the electrostatic and steric similarity of lactam compounds and the natural substrate for bacterial cell-wall biosynthesis

NASA Astrophysics Data System (ADS)

Frau, J.; Price, S. L.

1996-04-01

Electrostatic and structural properties of a set of β-lactam, γ-lactam and nonlactam compounds have been analyzed and compared with those of a model of the natural substrate d-alanyl- d-alanine for the carboxy- and transpeptidase enzymes. This first comparison of the electrostatic properties has been based on a distributed multipole analysis of high-quality ab initio wave functions of the substrate and potential antibiotics. The electrostatic similarity of the substrate and active compounds is apparent, and contrasts with the electrostatic properties of the noninhibitors. This has been quantified to give a reasonable correlation with the MIC (Minimum Concentration for Inhibition) and with kinetic data (k2/K) in accordance with the model for interaction of the lactam compounds with dd-peptidase. These correlations provide a better prediction of antibacterial activity than purely structural criteria.

ClusPro: an automated docking and discrimination method for the prediction of protein complexes.

PubMed

Comeau, Stephen R; Gatchell, David W; Vajda, Sandor; Camacho, Carlos J

2004-01-01

Predicting protein interactions is one of the most challenging problems in functional genomics. Given two proteins known to interact, current docking methods evaluate billions of docked conformations by simple scoring functions, and in addition to near-native structures yield many false positives, i.e. structures with good surface complementarity but far from the native. We have developed a fast algorithm for filtering docked conformations with good surface complementarity, and ranking them based on their clustering properties. The free energy filters select complexes with lowest desolvation and electrostatic energies. Clustering is then used to smooth the local minima and to select the ones with the broadest energy wells-a property associated with the free energy at the binding site. The robustness of the method was tested on sets of 2000 docked conformations generated for 48 pairs of interacting proteins. In 31 of these cases, the top 10 predictions include at least one near-native complex, with an average RMSD of 5 A from the native structure. The docking and discrimination method also provides good results for a number of complexes that were used as targets in the Critical Assessment of PRedictions of Interactions experiment. The fully automated docking and discrimination server ClusPro can be found at http://structure.bu.edu

3dRPC: a web server for 3D RNA-protein structure prediction.

PubMed

Huang, Yangyu; Li, Haotian; Xiao, Yi

2018-04-01

RNA-protein interactions occur in many biological processes. To understand the mechanism of these interactions one needs to know three-dimensional (3D) structures of RNA-protein complexes. 3dRPC is an algorithm for prediction of 3D RNA-protein complex structures and consists of a docking algorithm RPDOCK and a scoring function 3dRPC-Score. RPDOCK is used to sample possible complex conformations of an RNA and a protein by calculating the geometric and electrostatic complementarities and stacking interactions at the RNA-protein interface according to the features of atom packing of the interface. 3dRPC-Score is a knowledge-based potential that uses the conformations of nucleotide-amino-acid pairs as statistical variables and that is used to choose the near-native complex-conformations obtained from the docking method above. Recently, we built a web server for 3dRPC. The users can easily use 3dRPC without installing it locally. RNA and protein structures in PDB (Protein Data Bank) format are the only needed input files. It can also incorporate the information of interface residues or residue-pairs obtained from experiments or theoretical predictions to improve the prediction. The address of 3dRPC web server is http://biophy.hust.edu.cn/3dRPC. yxiao@hust.edu.cn.

Structural variability and the nature of intermolecular interactions in Watson-Crick B-DNA base pairs.

PubMed

Czyznikowska, Z; Góra, R W; Zaleśny, R; Lipkowski, P; Jarzembska, K N; Dominiak, P M; Leszczynski, J

2010-07-29

A set of nearly 100 crystallographic structures was analyzed using ab initio methods in order to verify the effect of the conformational variability of Watson-Crick guanine-cytosine and adenine-thymine base pairs on the intermolecular interaction energy and its components. Furthermore, for the representative structures, a potential energy scan of the structural parameters describing mutual orientation of the base pairs was carried out. The results were obtained using the hybrid variational-perturbational interaction energy decomposition scheme. The electron correlation effects were estimated by means of the second-order Møller-Plesset perturbation theory and coupled clusters with singles and doubles method adopting AUG-cc-pVDZ basis set. Moreover, the characteristics of hydrogen bonds in complexes, mimicking those appearing in B-DNA, were evaluated using topological analysis of the electron density. Although the first-order electrostatic energy is usually the largest stabilizing component, it is canceled out by the associated exchange repulsion in majority of the studied crystallographic structures. Therefore, the analyzed complexes of the nucleic acid bases appeared to be stabilized mainly by the delocalization component of the intermolecular interaction energy which, in terms of symmetry adapted perturbation theory, encompasses the second- and higher-order induction and exchange-induction terms. Furthermore, it was found that the dispersion contribution, albeit much smaller in terms of magnitude, is also a vital stabilizing factor. It was also revealed that the intermolecular interaction energy and its components are strongly influenced by four (out of six) structural parameters describing mutual orientation of bases in Watson-Crick pairs, namely shear, stagger, stretch, and opening. Finally, as a part of a model study, much of the effort was devoted to an extensive testing of the UBDB databank. It was shown that the databank quite successfully reproduces the electrostatic energy determined with the aid of ab initio methods.

A theoretical study on the electronic structures and equilibrium constants evaluation of Deferasirox iron complexes.

PubMed

Salehi, Samie; Saljooghi, Amir Shokooh; Izadyar, Mohammad

2016-10-01

Elemental iron is essential for cellular growth and homeostasis but it is potentially toxic to the cells and tissues. Excess iron can contribute in tumor initiation and tumor growth. Obviously, in iron overload issues using an iron chelator in order to reduce iron concentration seems to be vital. This study presents the density functional theory calculations of the electronic structure and equilibrium constant for iron-deferasirox (Fe-DFX) complexes in the gas phase, water and DMSO. A comprehensive study was performed to investigate the Deferasirox-iron complexes in chelation therapy. Calculation was performed in CAMB3LYP/6-31G(d,p) to get the optimized structures for iron complexes in high and low spin states. Natural bond orbital and quantum theory of atoms in molecules analyses was carried out with B3LYP/6-311G(d,p) to understand the nature of complex bond character and electronic transition in complexes. Electrostatic potential effects on the complexes were evaluated using the CHelpG calculations. The results indicated that higher affinity for Fe(III) is not strictly a function of bond length but also the degree of Fe-X (X=O,N) covalent bonding. Based on the quantum reactivity parameters which have been investigated here, it is possible reasonable design of the new chelators to improve the chelator abilities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dynamics of Charged Species in Ionic-Neutral Block Copolymer and Surfactant Complexes [Structural Relaxation and Dynamics of Ionic-Neutral Block Copolymer Surfactant Complexes

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

Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.

Structure–property relationships of ionic block copolymer (BCP) surfactant complexes are critical toward the progress of favorable engineering design of efficient charge-transport materials. In this paper, molecular dynamics simulations are used to understand the dynamics of charged-neutral BCP and surfactant complexes. The dynamics are examined for two different systems: charged-neutral double-hydrophilic and hydrophobic–hydrophilic block copolymers with oppositely charged surfactant moieties. The dynamics of the surfactant head, tails, and charges are studied for five different BCP volume fractions. We observe that the dynamics of the different species solely depend on the balance between electrostatic and entropic interactions between the charged species andmore » the neutral monomers. The favorable hydrophobic–hydrophobic interactions and the unfavorable hydrophobic–hydrophilic interactions determine the mobilities of the monomers. The dynamical properties of the charge species influence complex formation. Structural relaxations exhibit length-scale dependent behavior, with slower relaxation at the radius of gyration length-scale and faster relaxation at the segmental length-scale, consistent with previous results. The dynamical analysis correlates ion-exchange kinetics to the self-assembly behavior of the complexes.« less

Dynamics of Charged Species in Ionic-Neutral Block Copolymer and Surfactant Complexes [Structural Relaxation and Dynamics of Ionic-Neutral Block Copolymer Surfactant Complexes

DOE PAGES

Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.; ...

2017-06-21

Structure–property relationships of ionic block copolymer (BCP) surfactant complexes are critical toward the progress of favorable engineering design of efficient charge-transport materials. In this paper, molecular dynamics simulations are used to understand the dynamics of charged-neutral BCP and surfactant complexes. The dynamics are examined for two different systems: charged-neutral double-hydrophilic and hydrophobic–hydrophilic block copolymers with oppositely charged surfactant moieties. The dynamics of the surfactant head, tails, and charges are studied for five different BCP volume fractions. We observe that the dynamics of the different species solely depend on the balance between electrostatic and entropic interactions between the charged species andmore » the neutral monomers. The favorable hydrophobic–hydrophobic interactions and the unfavorable hydrophobic–hydrophilic interactions determine the mobilities of the monomers. The dynamical properties of the charge species influence complex formation. Structural relaxations exhibit length-scale dependent behavior, with slower relaxation at the radius of gyration length-scale and faster relaxation at the segmental length-scale, consistent with previous results. The dynamical analysis correlates ion-exchange kinetics to the self-assembly behavior of the complexes.« less

DNA minor groove electrostatic potential: influence of sequence-specific transitions of the torsion angle gamma and deoxyribose conformations.

PubMed

Zhitnikova, M Y; Shestopalova, A V

2017-11-01

The structural adjustments of the sugar-phosphate DNA backbone (switching of the γ angle (O5'-C5'-C4'-C3') from canonical to alternative conformations and/or C2'-endo → C3'-endo transition of deoxyribose) lead to the sequence-specific changes in accessible surface area of both polar and non-polar atoms of the grooves and the polar/hydrophobic profile of the latter ones. The distribution of the minor groove electrostatic potential is likely to be changing as a result of such conformational rearrangements in sugar-phosphate DNA backbone. Our analysis of the crystal structures of the short free DNA fragments and calculation of their electrostatic potentials allowed us to determine: (1) the number of classical and alternative γ angle conformations in the free B-DNA; (2) changes in the minor groove electrostatic potential, depending on the conformation of the sugar-phosphate DNA backbone; (3) the effect of the DNA sequence on the minor groove electrostatic potential. We have demonstrated that the structural adjustments of the DNA double helix (the conformations of the sugar-phosphate backbone and the minor groove dimensions) induce changes in the distribution of the minor groove electrostatic potential and are sequence-specific. Therefore, these features of the minor groove sizes and distribution of minor groove electrostatic potential can be used as a signal for recognition of the target DNA sequence by protein in the implementation of the indirect readout mechanism.

Structural basis for spectrin recognition by ankyrin.

PubMed

Ipsaro, Jonathan J; Mondragón, Alfonso

2010-05-20

Maintenance of membrane integrity and organization in the metazoan cell is accomplished through intracellular tethering of membrane proteins to an extensive, flexible protein network. Spectrin, the principal component of this network, is anchored to membrane proteins through the adaptor protein ankyrin. To elucidate the atomic basis for this interaction, we determined a crystal structure of human betaI-spectrin repeats 13 to 15 in complex with the ZU5-ANK domain of human ankyrin R. The structure reveals the role of repeats 14 to 15 in binding, the electrostatic and hydrophobic contributions along the interface, and the necessity for a particular orientation of the spectrin repeats. Using structural and biochemical data as a guide, we characterized the individual proteins and their interactions by binding and thermal stability analyses. In addition to validating the structural model, these data provide insight into the nature of some mutations associated with cell morphology defects, including those found in human diseases such as hereditary spherocytosis and elliptocytosis. Finally, analysis of the ZU5 domain suggests it is a versatile protein-protein interaction module with distinct interaction surfaces. The structure represents not only the first of a spectrin fragment in complex with its binding partner, but also that of an intermolecular complex involving a ZU5 domain.

Crystal structure and functional interpretation of the erythrocyte spectrin tetramerization domain complex

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

Ipsaro, Jonathan J.; Harper, Sandra L.; Messick, Troy E.

2010-09-07

As the principal component of the membrane skeleton, spectrin confers integrity and flexibility to red cell membranes. Although this network involves many interactions, the most common hemolytic anemia mutations that disrupt erythrocyte morphology affect the spectrin tetramerization domains. Although much is known clinically about the resulting conditions (hereditary elliptocytosis and pyropoikilocytosis), the detailed structural basis for spectrin tetramerization and its disruption by hereditary anemia mutations remains elusive. Thus, to provide further insights into spectrin assembly and tetramer site mutations, a crystal structure of the spectrin tetramerization domain complex has been determined. Architecturally, this complex shows striking resemblance to multirepeat spectrinmore » fragments, with the interacting tetramer site region forming a central, composite repeat. This structure identifies conformational changes in {alpha}-spectrin that occur upon binding to {beta}-spectrin, and it reports the first structure of the {beta}-spectrin tetramerization domain. Analysis of the interaction surfaces indicates an extensive interface dominated by hydrophobic contacts and supplemented by electrostatic complementarity. Analysis of evolutionarily conserved residues suggests additional surfaces that may form important interactions. Finally, mapping of hereditary anemia-related mutations onto the structure demonstrate that most, but not all, local hereditary anemia mutations map to the interacting domains. The potential molecular effects of these mutations are described.« less

Crystal Structure and Functional Interpretation of the Erythrocyte spectrin Tetramerization Domain Complex

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

J Ipsaro; S Harper; T Messick

2011-12-31

As the principal component of the membrane skeleton, spectrin confers integrity and flexibility to red cell membranes. Although this network involves many interactions, the most common hemolytic anemia mutations that disrupt erythrocyte morphology affect the spectrin tetramerization domains. Although much is known clinically about the resulting conditions (hereditary elliptocytosis and pyropoikilocytosis), the detailed structural basis for spectrin tetramerization and its disruption by hereditary anemia mutations remains elusive. Thus, to provide further insights into spectrin assembly and tetramer site mutations, a crystal structure of the spectrin tetramerization domain complex has been determined. Architecturally, this complex shows striking resemblance to multirepeat spectrinmore » fragments, with the interacting tetramer site region forming a central, composite repeat. This structure identifies conformational changes in {alpha}-spectrin that occur upon binding to {beta}-spectrin, and it reports the first structure of the {beta}-spectrin tetramerization domain. Analysis of the interaction surfaces indicates an extensive interface dominated by hydrophobic contacts and supplemented by electrostatic complementarity. Analysis of evolutionarily conserved residues suggests additional surfaces that may form important interactions. Finally, mapping of hereditary anemia-related mutations onto the structure demonstrate that most, but not all, local hereditary anemia mutations map to the interacting domains. The potential molecular effects of these mutations are described.« less

Statistical field theory description of inhomogeneous polarizable soft matter

NASA Astrophysics Data System (ADS)

Martin, Jonathan M.; Li, Wei; Delaney, Kris T.; Fredrickson, Glenn H.

2016-10-01

We present a new molecularly informed statistical field theory model of inhomogeneous polarizable soft matter. The model is based on fluid elements, referred to as beads, that can carry a net monopole of charge at their center of mass and a fixed or induced dipole through a Drude-type distributed charge approach. The beads are thus polarizable and naturally manifest attractive van der Waals interactions. Beyond electrostatic interactions, beads can be given soft repulsions to sustain fluid phases at arbitrary densities. Beads of different types can be mixed or linked into polymers with arbitrary chain models and sequences of charged and uncharged beads. By such an approach, it is possible to construct models suitable for describing a vast range of soft-matter systems including electrolyte and polyelectrolyte solutions, ionic liquids, polymerized ionic liquids, polymer blends, ionomers, and block copolymers, among others. These bead models can be constructed in virtually any ensemble and converted to complex-valued statistical field theories by Hubbard-Stratonovich transforms. One of the fields entering the resulting theories is a fluctuating electrostatic potential; other fields are necessary to decouple non-electrostatic interactions. We elucidate the structure of these field theories, their consistency with macroscopic electrostatic theory in the absence and presence of external electric fields, and the way in which they embed van der Waals interactions and non-uniform dielectric properties. Their suitability as a framework for computational studies of heterogeneous soft matter systems using field-theoretic simulation techniques is discussed.

MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations

NASA Astrophysics Data System (ADS)

Vergara-Perez, Sandra; Marucho, Marcelo

2016-01-01

One of the most used and efficient approaches to compute electrostatic properties of biological systems is to numerically solve the Poisson-Boltzmann (PB) equation. There are several software packages available that solve the PB equation for molecules in aqueous electrolyte solutions. Most of these software packages are useful for scientists with specialized training and expertise in computational biophysics. However, the user is usually required to manually take several important choices, depending on the complexity of the biological system, to successfully obtain the numerical solution of the PB equation. This may become an obstacle for researchers, experimentalists, even students with no special training in computational methodologies. Aiming to overcome this limitation, in this article we present MPBEC, a free, cross-platform, open-source software that provides non-experts in the field an easy and efficient way to perform biomolecular electrostatic calculations on single processor computers. MPBEC is a Matlab script based on the Adaptative Poisson-Boltzmann Solver, one of the most popular approaches used to solve the PB equation. MPBEC does not require any user programming, text editing or extensive statistical skills, and comes with detailed user-guide documentation. As a unique feature, MPBEC includes a useful graphical user interface (GUI) application which helps and guides users to configure and setup the optimal parameters and approximations to successfully perform the required biomolecular electrostatic calculations. The GUI also incorporates visualization tools to facilitate users pre- and post-analysis of structural and electrical properties of biomolecules.

MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations

PubMed Central

Vergara-Perez, Sandra; Marucho, Marcelo

2015-01-01

One of the most used and efficient approaches to compute electrostatic properties of biological systems is to numerically solve the Poisson-Boltzmann (PB) equation. There are several software packages available that solve the PB equation for molecules in aqueous electrolyte solutions. Most of these software packages are useful for scientists with specialized training and expertise in computational biophysics. However, the user is usually required to manually take several important choices, depending on the complexity of the biological system, to successfully obtain the numerical solution of the PB equation. This may become an obstacle for researchers, experimentalists, even students with no special training in computational methodologies. Aiming to overcome this limitation, in this article we present MPBEC, a free, cross-platform, open-source software that provides non-experts in the field an easy and efficient way to perform biomolecular electrostatic calculations on single processor computers. MPBEC is a Matlab script based on the Adaptative Poisson Boltzmann Solver, one of the most popular approaches used to solve the PB equation. MPBEC does not require any user programming, text editing or extensive statistical skills, and comes with detailed user-guide documentation. As a unique feature, MPBEC includes a useful graphical user interface (GUI) application which helps and guides users to configure and setup the optimal parameters and approximations to successfully perform the required biomolecular electrostatic calculations. The GUI also incorporates visualization tools to facilitate users pre- and post- analysis of structural and electrical properties of biomolecules. PMID:26924848

MPBEC, a Matlab Program for Biomolecular Electrostatic Calculations.

PubMed

Vergara-Perez, Sandra; Marucho, Marcelo

2016-01-01

One of the most used and efficient approaches to compute electrostatic properties of biological systems is to numerically solve the Poisson-Boltzmann (PB) equation. There are several software packages available that solve the PB equation for molecules in aqueous electrolyte solutions. Most of these software packages are useful for scientists with specialized training and expertise in computational biophysics. However, the user is usually required to manually take several important choices, depending on the complexity of the biological system, to successfully obtain the numerical solution of the PB equation. This may become an obstacle for researchers, experimentalists, even students with no special training in computational methodologies. Aiming to overcome this limitation, in this article we present MPBEC, a free, cross-platform, open-source software that provides non-experts in the field an easy and efficient way to perform biomolecular electrostatic calculations on single processor computers. MPBEC is a Matlab script based on the Adaptative Poisson Boltzmann Solver, one of the most popular approaches used to solve the PB equation. MPBEC does not require any user programming, text editing or extensive statistical skills, and comes with detailed user-guide documentation. As a unique feature, MPBEC includes a useful graphical user interface (GUI) application which helps and guides users to configure and setup the optimal parameters and approximations to successfully perform the required biomolecular electrostatic calculations. The GUI also incorporates visualization tools to facilitate users pre- and post- analysis of structural and electrical properties of biomolecules.

Statistical field theory description of inhomogeneous polarizable soft matter.

PubMed

Martin, Jonathan M; Li, Wei; Delaney, Kris T; Fredrickson, Glenn H

2016-10-21

We present a new molecularly informed statistical field theory model of inhomogeneous polarizable soft matter. The model is based on fluid elements, referred to as beads, that can carry a net monopole of charge at their center of mass and a fixed or induced dipole through a Drude-type distributed charge approach. The beads are thus polarizable and naturally manifest attractive van der Waals interactions. Beyond electrostatic interactions, beads can be given soft repulsions to sustain fluid phases at arbitrary densities. Beads of different types can be mixed or linked into polymers with arbitrary chain models and sequences of charged and uncharged beads. By such an approach, it is possible to construct models suitable for describing a vast range of soft-matter systems including electrolyte and polyelectrolyte solutions, ionic liquids, polymerized ionic liquids, polymer blends, ionomers, and block copolymers, among others. These bead models can be constructed in virtually any ensemble and converted to complex-valued statistical field theories by Hubbard-Stratonovich transforms. One of the fields entering the resulting theories is a fluctuating electrostatic potential; other fields are necessary to decouple non-electrostatic interactions. We elucidate the structure of these field theories, their consistency with macroscopic electrostatic theory in the absence and presence of external electric fields, and the way in which they embed van der Waals interactions and non-uniform dielectric properties. Their suitability as a framework for computational studies of heterogeneous soft matter systems using field-theoretic simulation techniques is discussed.

Prediction of protein-protein interaction sites using electrostatic desolvation profiles.

PubMed

Fiorucci, Sébastien; Zacharias, Martin

2010-05-19

Protein-protein complex formation involves removal of water from the interface region. Surface regions with a small free energy penalty for water removal or desolvation may correspond to preferred interaction sites. A method to calculate the electrostatic free energy of placing a neutral low-dielectric probe at various protein surface positions has been designed and applied to characterize putative interaction sites. Based on solutions of the finite-difference Poisson equation, this method also includes long-range electrostatic contributions and the protein solvent boundary shape in contrast to accessible-surface-area-based solvation energies. Calculations on a large set of proteins indicate that in many cases (>90%), the known binding site overlaps with one of the six regions of lowest electrostatic desolvation penalty (overlap with the lowest desolvation region for 48% of proteins). Since the onset of electrostatic desolvation occurs even before direct protein-protein contact formation, it may help guide proteins toward the binding region in the final stage of complex formation. It is interesting that the probe desolvation properties associated with residue types were found to depend to some degree on whether the residue was outside of or part of a binding site. The probe desolvation penalty was on average smaller if the residue was part of a binding site compared to other surface locations. Applications to several antigen-antibody complexes demonstrated that the approach might be useful not only to predict protein interaction sites in general but to map potential antigenic epitopes on protein surfaces. Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Self organization of exotic oil-in-oil phases driven by tunable electrohydrodynamics

PubMed Central

Varshney, Atul; Ghosh, Shankar; Bhattacharya, S.; Yethiraj, Anand

2012-01-01

Self organization of large-scale structures in nature - either coherent structures like crystals, or incoherent dynamic structures like clouds - is governed by long-range interactions. In many problems, hydrodynamics and electrostatics are the source of such long-range interactions. The tuning of electrostatic interactions has helped to elucidate when coherent crystalline structures or incoherent amorphous structures form in colloidal systems. However, there is little understanding of self organization in situations where both electrostatic and hydrodynamic interactions are present. We present a minimal two-component oil-in-oil model system where we can control the strength and lengthscale of the electrohydrodynamic interactions by tuning the amplitude and frequency of the imposed electric field. As a function of the hydrodynamic lengthscale, we observe a rich phenomenology of exotic structure and dynamics, from incoherent cloud-like structures and chaotic droplet dynamics, to polyhedral droplet phases, to coherent droplet arrays. PMID:23071902

X-ray structure of the mammalian GIRK2-βγ G-protein complex

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

Whorton, Matthew R.; MacKinnon, Roderick

2013-07-30

G-protein-gated inward rectifier K + (GIRK) channels allow neurotransmitters, through G-protein-coupled receptor stimulation, to control cellular electrical excitability. In cardiac and neuronal cells this control regulates heart rate and neural circuit activity, respectively. Here we present the 3.5Å resolution crystal structure of the mammalian GIRK2 channel in complex with βγ G-protein subunits, the central signalling complex that links G-protein-coupled receptor stimulation to K + channel activity. Short-range atomic and long-range electrostatic interactions stabilize four βγ G-protein subunits at the interfaces between four K + channel subunits, inducing a pre-open state of the channel. The pre-open state exhibits a conformation thatmore » is intermediate between the closed conformation and the open conformation of the constitutively active mutant. The resultant structural picture is compatible with ‘membrane delimited’ activation of GIRK channels by G proteins and the characteristic burst kinetics of channel gating. The structures also permit a conceptual understanding of how the signalling lipid phosphatidylinositol-4,5-bisphosphate (PIP 2) and intracellular Na + ions participate in multi-ligand regulation of GIRK channels.« less

Porous polycarbene-bearing membrane actuator for ultrasensitive weak-acid detection and real-time chemical reaction monitoring.

PubMed

Sun, Jian-Ke; Zhang, Weiyi; Guterman, Ryan; Lin, Hui-Juan; Yuan, Jiayin

2018-04-30

Soft actuators with integration of ultrasensitivity and capability of simultaneous interaction with multiple stimuli through an entire event ask for a high level of structure complexity, adaptability, and/or multi-responsiveness, which is a great challenge. Here, we develop a porous polycarbene-bearing membrane actuator built up from ionic complexation between a poly(ionic liquid) and trimesic acid (TA). The actuator features two concurrent structure gradients, i.e., an electrostatic complexation (EC) degree and a density distribution of a carbene-NH 3 adduct (CNA) along the membrane cross-section. The membrane actuator performs the highest sensitivity among the state-of-the-art soft proton actuators toward acetic acid at 10 -6  mol L -1 (M) level in aqueous media. Through competing actuation of the two gradients, it is capable of monitoring an entire process of proton-involved chemical reactions that comprise multiple stimuli and operational steps. The present achievement constitutes a significant step toward real-life application of soft actuators in chemical sensing and reaction technology.

MALDI mass spectrometry of dye-peptide and dye-protein complexes.

PubMed

Salih, B; Zenobi, R

1998-04-15

Immobilized sulfonate dyes are widely used for protein separation and purification, but the mode of interaction between the dye molecules and the proteins is largely unknown. Here we show that specific noncovalent dye-protein and dye-peptide complexes can be observed using MALDI mass spectrometry. We prove that the interaction is prodominantly electrostatic and that it involves protonated sites of the peptides and proteins, including the NH2 terminus, and deprotonated SO3 groups of the dyes. Furthermore, we show that MALDI-MS of such complexes with a nonacidic matrix, p-nitro-aniline, can be used to determine the number of accessible basic sites of a protein or peptide in its folded structure. Our results are in good agreement with measurements of the same property done with electrospray ionization.

Interaction surface and topology of Get3-Get4-Get5 protein complex, involved in targeting tail-anchored proteins to endoplasmic reticulum.

PubMed

Chang, Yi-Wei; Lin, Tai-Wen; Li, Yi-Chuan; Huang, Yu-Shan; Sun, Yuh-Ju; Hsiao, Chwan-Deng

2012-02-10

Recent work has uncovered the "GET system," which is responsible for endoplasmic reticulum targeting of tail-anchored proteins. Although structural information and the individual roles of most components of this system have been defined, the interactions and interplay between them remain to be elucidated. Here, we investigated the interactions between Get3 and the Get4-Get5 complex from Saccharomyces cerevisiae. We show that Get3 interacts with Get4-Get5 via an interface dominated by electrostatic forces. Using isothermal titration calorimetry and small-angle x-ray scattering, we further demonstrate that the Get3 homodimer interacts with two copies of the Get4-Get5 complex to form an extended conformation in solution.

Electrostatic Solvation Free Energy of Amino Acid Side Chain Analogs: Implications for the Validity of Electrostatic Linear Response in Water

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

Lin, Bin; Pettitt, Bernard M.

Electrostatic free energies of solvation for 15 neutral amino acid side chain analogs are computed. We compare three methods of varying computational complexity and accuracy for three force fields: free energy simulations, Poisson-Boltzmann (PB), and linear response approximation (LRA) using AMBER, CHARMM, and OPLSAA force fields. We find that deviations from simulation start at low charges for solutes. The approximate PB and LRA produce an overestimation of electrostatic solvation free energies for most of molecules studied here. These deviations are remarkably systematic. The variations among force fields are almost as large as the variations found among methods. Our study confirmsmore » that success of the approximate methods for electrostatic solvation free energies comes from their ability to evaluate free energy differences accurately.« less

An uracil-linked hydroxyflavone probe for the recognition of ATP

PubMed Central

Bojtár, Márton; Janzsó-Berend, Péter Zoltán; Mester, Dávid; Hessz, Dóra; Kállay, Mihály; Kubinyi, Miklós

2018-01-01

Background: Nucleotides are essential molecules in living systems due to their paramount importance in various physiological processes. In the past years, numerous attempts were made to selectively recognize and detect these analytes, especially ATP using small-molecule fluorescent chemosensors. Despite the various solutions, the selective detection of ATP is still challenging due to the structural similarity of various nucleotides. In this paper, we report the conjugation of a uracil nucleobase to the known 4’-dimethylamino-hydroxyflavone fluorophore. Results: The complexation of this scaffold with ATP is already known. The complex is held together by stacking and electrostatic interactions. To achieve multi-point recognition, we designed the uracil-appended version of this probe to include complementary base-pairing interactions. The theoretical calculations revealed the availability of multiple complex structures. The synthesis was performed using click chemistry and the nucleotide recognition properties of the probe were evaluated using fluorescence spectroscopy. Conclusions: The first, uracil-containing fluorescent ATP probe based on a hydroxyflavone fluorophore was synthesized and evaluated. A selective complexation with ATP was observed and a ratiometric response in the excitation spectrum. PMID:29719572

Ultrafast and low barrier motions in the photoreactions of the green fluorescent protein.

PubMed

van Thor, Jasper J; Georgiev, Georgi Y; Towrie, Michael; Sage, J Timothy

2005-09-30

Green fluorescent protein (GFP) fluoresces efficiently under blue excitation despite major electrostatic rearrangements resulting from photoionization of the chromophore and neutralization of Glu-222. A competing phototransformation process, which ionizes the chromophore and decarboxylates Glu-222, mimics the electrostatic and structural changes in the fluorescence photocycle. Structural and spectroscopic analysis of the cryogenically stabilized photoproduct at 100 K and a structurally annealed intermediate of the phototransformed protein at 170 K reveals distinct structural relaxations involving protein, chromophore, solvent, and photogenerated CO2. Strong structural changes of the 100 K photoproduct after decarboxylation appear exclusively within 15 angstroms of the chromophore and include the electrostatically driven perturbations of Gln-69, Cys-70, and water molecules in an H-bonding network connecting the chromophore. X-ray crystallography to 1.85 angstroms resolution and static and picosecond time-resolved IR spectroscopy identify structural mechanisms common to phototransformation and to the fluorescence photocycle. In particular, the appearance of a 1697 cm(-1) (+) difference band in both photocycle and phototransformation intermediates is a spectroscopic signature for the structural perturbation of Gln-69. This is taken as evidence for an electrostatically driven dynamic response that is common to both photoreaction pathways. The interactions between the chromophore and the perturbed residues and solvent are decreased or removed in the T203H single and T203H/Q69L double mutants, resulting in a strong reduction of the fluorescence quantum yield. This suggests that the electrostatic response to the transient formation of a buried charge in the wild type is important for the bright fluorescence.

Electrostatic Levitation Technique for Investigations of Physical Properties of Liquid States

NASA Astrophysics Data System (ADS)

Okada, Junpei; Ishikawa, Takehiko; Paradis, Paul-Francois; Yoda, Shinichi

Electrostatic levitator (ESL) levitates a charged sample in a high vacuum using computer con-trolled electrostatic fields [1]. It can levitate materials such as metals, semiconductors, and some insulators. Sample temperature can be varied over a wide range, and samples can be deeply undercooled. We have been engaged in the research and development of the electro-static levitation technique with the aim of performing levitation dissolution experiments in the International Space Station (ISS). Our device for the electrostatic levitation dissolution test has been developed for experiments on the ISS. To this end, the system is designed to be compact and portable so that it can be launched by rocket and used for experiments in the limited space on the ISS. Accordingly, the device can be installed not just on the ISS or our research laboratory, but also in various external sites. We devised a plan to install the electrostatic levitation system in a site other than the ISS to study atomic structure and electron structure of ultra-high-temperature liquids. We mounted our system on third generation synchrotron radiation facility "SPring-8" in Japan, to investigate the atomic and electron structures of high-temperature liquids. The SPring-8 is an experimental facility that allows use of the most powerful X-rays in the world. We conducted a variety of experiments on ultra-high-temperature liquids using SPring-8. The X-ray is ideal for exploring atomic structure and electron structure. Since the X-ray is an electromagnetic wave, it interacts with electrons. In addition, most electrons gather around the atomic nucleus. By close analysis of the scattered x-rays, we can determine its atomic structure and electron structure in detail. In this talk, we introduce an x-ray Compton scattering and x-ray Raman scattering measurements on liquid aluminum and silicon. [1] W. -K. Rhim, et al, Rev. Sci. Instrum. (1985) 56 307.

Electrostatic Interactions and Self-Assembly in Polymeric Systems

NASA Astrophysics Data System (ADS)

Dobrynin, Andrey

Electrostatic interactions between macroions play an important role in different areas ranging from materials science to biophysics. They are main driving forces behind layer-by-layer assembly technique that allows self-assembly of multilayer films from synthetic polyelectrolytes, DNA, proteins and nanoparticles. They are responsible for complexation and reversible gelation between polyelectrolytes and proteins. In this talk, using results of the molecular dynamics simulations and analytical calculations, I will demonstrate what effect electrostatic interactions, counterion condensation and polymer solvent affinity have on a collapse of polyelectrolyte chain in a poor solvent conditions for the polymer backbone, on complexations and reversible gelation between polyelectrolytes and polyamholytes (unstructured proteins), on microphase separation transitions in spherical and planar charged brushes, and on a layer-by-layer assembly of charged nanoparticles and linear polyelectrolytes on charged surfaces. NSF DMR-1004576 DMR-1409710.

Exploration of electrostatic interaction in the hydrophobic pocket of lysozyme: Importance of ligand-induced perturbation of the secondary structure on the mode of binding of exogenous ligand and possible consequences.

PubMed

Panja, Sudipta; Halder, Mintu

2016-08-01

Exogenous ligand binding can be adequate to alter the secondary structure of biomolecules besides other external stimuli. In such cases, structural alterations can complicate on the nature of interaction with the exogenous molecules. In order to accommodate the exogenous ligand, the biomolecule has to unfold resulting in a considerable change to its properties. If the bound ligand can be unbound, the biomolecule gets the opportunity to refold back and return to its native state. Keeping this in mind, we have purposely investigated the interaction of tartrazine (TZ), a well abundant azo food colorant, with two homologous lysozymes, namely, human lysozyme (HLZ) and chicken egg white lysozyme (CEWLZ) in physiological pH condition. The binding of TZ with lysozymes has been identified to accompany a ligand-induced secondary structure alteration as indicated by the circular dichroism spectra, and the reduction of α-helical content is more with HLZ than CEWLZ. Interestingly, the binding is identified to occur in the electronic ground state of TZ with lysozyme in its hydrophobic cavity, containing excess of positive charge, predominantly via electrostatic interaction. With increase of salinity of the medium the protein tends to refold back due to wakening of electrostatic forces and consequent reduction of strength of ligand interaction and unbinding. The entropy enthalpy compensation (EEC) has been probed to understand the binding features and it is found that CEWLZ-TZ shows better compensation than HLZ-TZ complex. This is presumably due to the fact that with CEWLZ the binding does not accompany substantial change in the protein secondary structure and hence ineffective to scramble the EEC. The present study initiates the importance of ligand-perturbed structural alteration of biomolecule in controlling the thermodynamics of binding. If there is a considerable alteration of the protein secondary structure due to binding, it is indicative that such changes should bring in the overall loss of activity of protein. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanism of the formation of the RecA-ssDNA nucleoprotein filament structure: a coarse-grained approach.

PubMed

Mukherjee, Goutam; Pal, Arumay; Levy, Yaakov

2017-11-21

In prokaryotes, the RecA protein catalyzes the repair and strand exchange of double-stranded DNA. RecA binds to single-stranded DNA (ssDNA) and forms a presynaptic complex in which the protein polymerizes around the ssDNA to form a right-handed helical nucleoprotein filament structure. In the present work, the mechanism for the formation of the RecA-ssDNA filament structure is modeled using coarse-grained molecular dynamics simulations. Information from the X-ray structure was used to model the protein itself but not its interactions; the interactions between the protein and the ssDNA were modeled solely by electrostatic, aromatic, and repulsive energies. For the present study, the monomeric, dimeric, and trimeric units of RecA and 4, 8, and 11 NT-long ssDNA, respectively, were studied. Our results indicate that monomeric RecA is not sufficient for nucleoprotein filament formation; rather, dimeric RecA is the elementary binding unit, with higher multimeric units of RecA facilitating filament formation. Our results reveal that loop region flexibility at the primary binding site of RecA is essential for it to bind the incoming ssDNA, that the aromatic residues present in the loop region play an important role in ssDNA binding, and that ATP may play a role in guiding the ssDNA by changing the electrostatic potential of the RecA protein.

Investigation of the basic characteristics of electrostatic shielding from cosmic radiations on the artificial earth satellite Kosmos 605. I. Measurement procedure and the complex of scientific apparatus. [1. 4 x 10/sup 7/ V/m

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

Kovalev, E.E.; Molchanov, E.D.; Pekhterev, Yu.G.

1975-01-01

The complex of scientific apparatus installed on board the artifical earth satellite Kosmos 605 for the creation of electric fields near the satellite with intensities up to 1.4 x 10/sup 7/ V/m and for direct measurements of conduction currents of a high voltage vacuum interval for the purpose of determining the basic characteristics of electrostatic shielding from cosmic radiations is described.

The electrostatic role of the Zn-Cys2His2 complex in binding of operator DNA with transcription factors: mouse EGR-1 from the Cys2His2 family.

PubMed

Chirgadze, Y N; Boshkova, E A; Polozov, R V; Sivozhelezov, V S; Dzyabchenko, A V; Kuzminsky, M B; Stepanenko, V A; Ivanov, V V

2018-01-07

The mouse factor Zif268, known also as early growth response protein EGR-1, is a classical representative for the Cys2His2 transcription factor family. It is required for binding the RNA polymerase with operator dsDNA to initialize the transcription process. We have shown that only in this family of total six Zn-finger protein families the Zn complex plays a significant role in the protein-DNA binding. Electrostatic feature of this complex in the binding of factor Zif268 from Mus musculus with operator DNA has been considered. The factor consists of three similar Zn-finger units which bind with triplets of coding DNA. Essential contacts of the factor with the DNA phosphates are formed by three conservative His residues, one in each finger. We describe here the results of calculations of the electrostatic potentials for the Zn-Cys2His2 complex, Zn-finger unit 1, and the whole transcription factor. The potential of Zif268 has a positive area on the factor surface, and it corresponds exactly to the binding sites of each of Zn-finger units. The main part of these areas is determined by conservative His residues, which form contacts with the DNA phosphate groups. Our result shows that the electrostatic positive potential of this histidine residue is enhanced due to the Zn complex. The other contacts of the Zn-finger with DNA are related to nucleotide bases, and they are responsible for the sequence-specific binding with DNA. This result may be extended to all other members of the Cys2His2 transcription factor family.

A Nonlinear Elasticity Model of Macromolecular Conformational Change Induced by Electrostatic Forces

PubMed Central

Zhou, Y. C.; Holst, Michael; McCammon, J. Andrew

2008-01-01

In this paper we propose a nonlinear elasticity model of macromolecular conformational change (deformation) induced by electrostatic forces generated by an implicit solvation model. The Poisson-Boltzmann equation for the electrostatic potential is analyzed in a domain varying with the elastic deformation of molecules, and a new continuous model of the electrostatic forces is developed to ensure solvability of the nonlinear elasticity equations. We derive the estimates of electrostatic forces corresponding to four types of perturbations to an electrostatic potential field, and establish the existance of an equilibrium configuration using a fixed-point argument, under the assumption that the change in the ionic strength and charges due to the additional molecules causing the deformation are sufficiently small. The results are valid for elastic models with arbitrarily complex dielectric interfaces and cavities, and can be generalized to large elastic deformation caused by high ionic strength, large charges, and strong external fields by using continuation methods. PMID:19461946

Complex coacervates as a foundation for synthetic underwater adhesives

PubMed Central

Stewart, Russell J.; Wang, Ching Shuen; Shao, Hui

2011-01-01

Complex coacervation was proposed to play a role in the formation of the underwater bioadhesive of the Sandcastle worm (Phragmatopoma californica) based on the polyacidic and polybasic nature of the glue proteins and the balance of opposite charges at physiological pH. Morphological studies of the secretory system suggested the natural process does not involve complex coacervation as commonly defined. The distinction may not be important because electrostatic interactions likely play an important role in formation of the sandcastle glue. Complex coacervation has also been invoked in the formation of adhesive underwater silk fibers of caddisfly larvae and the adhesive plaques of mussels. A process similar to complex coacervation, that is, condensation and dehydration of biopolyelectrolytes through electrostatic associations, seems plausible for the caddisfly silk. This much is clear, the sandcastle glue complex coacervation model provided a valuable blueprint for the synthesis of a biomimetic, waterborne, underwater adhesive with demonstrated potential for repair of wet tissue. PMID:21081223

Interaction between water-soluble rhodium complex RhCl(CO)(TPPTS)₂ and surfactants probed by spectroscopic methods.

PubMed

Zhou, Li-Mei; Guo, Cai-Hong; Fu, Hai-Yan; Jiang, Xiao-Hui; Chen, Hua; Li, Rui-Xiang; Li, Xian-Jun

2012-07-01

The interactions of rhodium complex RhCl(CO)(TPPTS)(2) [TPPTS=P(m-C(6)H(4)SO(3)Na)(3)] with cationic, nonionic, and anionic surfactants have been investigated by UV-vis, fluorescence and (1)H NMR measurements. The presence of four different species of RhCl(CO)(TPPTS)(2) in cationic cetyltrimethylammonium (CTAB) solution has been demonstrated: free rhodium complex, rhodium complex bound to CTAB monomer, rhodium complex bound to CTAB premicelles, rhodium complex bound to CTAB micelles. The spectroscopy data show that RhCl(CO)(TPPTS)(2) can adsorb on the interface of cationic CTAB micelles by strong electrostatic attraction, weakly bind to the nonionic polyoxyethylene (20) sorbitan monolaurate (Tween 20) micelles by hydrophobic interaction, and does not interact with anion sodium dodecyl sulfate (SDS) micelles due to the strong electrostatic repulsion. Copyright © 2012 Elsevier B.V. All rights reserved.

Advanced understanding on electronic structure of molecular semiconductors and their interfaces

NASA Astrophysics Data System (ADS)

Akaike, Kouki

2018-03-01

Understanding the electronic structure of organic semiconductors and their interfaces is critical to optimizing functionalities for electronics applications, by rational chemical design and appropriate combination of device constituents. The unique electronic structure of a molecular solid is characterized as (i) anisotropic electrostatic fields that originate from molecular quadrupoles, (ii) interfacial energy-level lineup governed by simple electrostatics, and (iii) weak intermolecular interactions that make not only structural order but also energy distributions of the frontier orbitals sensitive to atmosphere and interface growth. This article shows an overview on these features with reference to the improved understanding of the orientation-dependent electronic structure, comprehensive mechanisms of molecular doping, and energy-level alignment. Furthermore, the engineering of ionization energy by the control of the electrostatic fields and work function of practical electrodes by contact-induced doping is briefly described for the purpose of highlighting how the electronic structure impacts the performance of organic devices.

Theoretical insights into the π-hole interactions in the complexes containing triphosphorus hydride (P3H3) and its derivatives.

PubMed

Wang, Yuehong; Li, Xiaoyan; Zeng, Yanli; Meng, Lingpeng; Zhang, Xueying

2017-04-01

The π-hole of triphosphorus hydride (P 3 H 3 ) and its derivatives Z 3 X 3 (Z = P, As; X = H, F, Cl, Br) was discovered and analyzed. MP2/aug-cc-pVDZ calculations were performed on the π-hole interactions in the HCN...Z 3 X 3 complexes and the mutual influence between π-hole interactions and the hydrogen bond in the HCN...HCN...Z 3 X 3 and HCN...Z 3 X 3 ...HCN complexes studied. The π-hole interaction belongs to the typical closed-shell noncovalent interaction. The linear relationship was found between the most positive electrostatic potential of the π-hole (V S,max ) and the interaction energy. Moreover, the V S,max of the π-hole was also found to be linearly correlated to the electrostatic energy term, indicating the important contribution of the electrostatic energy term to the π-hole interaction. There is positive cooperativity between the π-hole interaction and the hydrogen bond in the termolecular complexes. The π-hole interaction has a greater influence on the hydrogen bond than vice versa. The mutual enhancing effect between the π-hole interaction and the hydrogen bond in the HCN...HCN...Z 3 X 3 complexes is greater than that in the HCN...Z 3 X 3 ...HCN complexes.

Hydration effects on the electrostatic potential around tuftsin.

PubMed

Valdeavella, C V; Blatt, H D; Yang, L; Pettitt, B M

1999-08-01

The electrostatic potential and component dielectric constants from molecular dynamics (MD) trajectories of tuftsin, a tetrapeptide with the amino acid sequence Thr-Lys-Pro-Arg in water and in saline solution are presented. The results obtained from the analysis of the MD trajectories for the total electrostatic potential at points on a grid using the Ewald technique are compared with the solution to the Poisson-Boltzmann (PB) equation. The latter was solved using several sets of dielectric constant parameters. The effects of structural averaging on the PB results were also considered. Solute conformational mobility in simulations gives rise to an electrostatic potential map around the solute dominated by the solute monopole (or lowest order multipole). The detailed spatial variation of the electrostatic potential on the molecular surface brought about by the compounded effects of the distribution of water and ions close to the peptide, solvent mobility, and solute conformational mobility are not qualitatively reproducible from a reparametrization of the input solute and solvent dielectric constants to the PB equation for a single structure or for structurally averaged PB calculations. Nevertheless, by fitting the PB to the MD electrostatic potential surfaces with the dielectric constants as fitting parameters, we found that the values that give the best fit are the values calculated from the MD trajectories. Implications of using such field calculations on the design of tuftsin peptide analogues are discussed.

An anisotropic hydrogel with electrostatic repulsion between cofacially aligned nanosheets

NASA Astrophysics Data System (ADS)

Liu, Mingjie; Ishida, Yasuhiro; Ebina, Yasuo; Sasaki, Takayoshi; Hikima, Takaaki; Takata, Masaki; Aida, Takuzo

2015-01-01

Machine technology frequently puts magnetic or electrostatic repulsive forces to practical use, as in maglev trains, vehicle suspensions or non-contact bearings. In contrast, materials design overwhelmingly focuses on attractive interactions, such as in the many advanced polymer-based composites, where inorganic fillers interact with a polymer matrix to improve mechanical properties. However, articular cartilage strikingly illustrates how electrostatic repulsion can be harnessed to achieve unparalleled functional efficiency: it permits virtually frictionless mechanical motion within joints, even under high compression. Here we describe a composite hydrogel with anisotropic mechanical properties dominated by electrostatic repulsion between negatively charged unilamellar titanate nanosheets embedded within it. Crucial to the behaviour of this hydrogel is the serendipitous discovery of cofacial nanosheet alignment in aqueous colloidal dispersions subjected to a strong magnetic field, which maximizes electrostatic repulsion and thereby induces a quasi-crystalline structural ordering over macroscopic length scales and with uniformly large face-to-face nanosheet separation. We fix this transiently induced structural order by transforming the dispersion into a hydrogel using light-triggered in situ vinyl polymerization. The resultant hydrogel, containing charged inorganic structures that align cofacially in a magnetic flux, deforms easily under shear forces applied parallel to the embedded nanosheets yet resists compressive forces applied orthogonally. We anticipate that the concept of embedding anisotropic repulsive electrostatics within a composite material, inspired by articular cartilage, will open up new possibilities for developing soft materials with unusual functions.

An anisotropic hydrogel with electrostatic repulsion between cofacially aligned nanosheets.

PubMed

Liu, Mingjie; Ishida, Yasuhiro; Ebina, Yasuo; Sasaki, Takayoshi; Hikima, Takaaki; Takata, Masaki; Aida, Takuzo

2015-01-01

Machine technology frequently puts magnetic or electrostatic repulsive forces to practical use, as in maglev trains, vehicle suspensions or non-contact bearings. In contrast, materials design overwhelmingly focuses on attractive interactions, such as in the many advanced polymer-based composites, where inorganic fillers interact with a polymer matrix to improve mechanical properties. However, articular cartilage strikingly illustrates how electrostatic repulsion can be harnessed to achieve unparalleled functional efficiency: it permits virtually frictionless mechanical motion within joints, even under high compression. Here we describe a composite hydrogel with anisotropic mechanical properties dominated by electrostatic repulsion between negatively charged unilamellar titanate nanosheets embedded within it. Crucial to the behaviour of this hydrogel is the serendipitous discovery of cofacial nanosheet alignment in aqueous colloidal dispersions subjected to a strong magnetic field, which maximizes electrostatic repulsion and thereby induces a quasi-crystalline structural ordering over macroscopic length scales and with uniformly large face-to-face nanosheet separation. We fix this transiently induced structural order by transforming the dispersion into a hydrogel using light-triggered in situ vinyl polymerization. The resultant hydrogel, containing charged inorganic structures that align cofacially in a magnetic flux, deforms easily under shear forces applied parallel to the embedded nanosheets yet resists compressive forces applied orthogonally. We anticipate that the concept of embedding anisotropic repulsive electrostatics within a composite material, inspired by articular cartilage, will open up new possibilities for developing soft materials with unusual functions.

New strategy for protein interactions and application to structure-based drug design

NASA Astrophysics Data System (ADS)

Zou, Xiaoqin

One of the greatest challenges in computational biophysics is to predict interactions between biological molecules, which play critical roles in biological processes and rational design of therapeutic drugs. Biomolecular interactions involve delicate interplay between multiple interactions, including electrostatic interactions, van der Waals interactions, solvent effect, and conformational entropic effect. Accurate determination of these complex and subtle interactions is challenging. Moreover, a biological molecule such as a protein usually consists of thousands of atoms, and thus occupies a huge conformational space. The large degrees of freedom pose further challenges for accurate prediction of biomolecular interactions. Here, I will present our development of physics-based theory and computational modeling on protein interactions with other molecules. The major strategy is to extract microscopic energetics from the information embedded in the experimentally-determined structures of protein complexes. I will also present applications of the methods to structure-based therapeutic design. Supported by NSF CAREER Award DBI-0953839, NIH R01GM109980, and the American Heart Association (Midwest Affiliate) [13GRNT16990076].

Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations.

PubMed

De Simone, Giuseppina; Langella, Emma; Esposito, Davide; Supuran, Claudiu T; Monti, Simona Maria; Winum, Jean-Yves; Alterio, Vincenzo

2017-12-01

Sulphamate and sulphamide derivatives have been largely investigated as carbonic anhydrase inhibitors (CAIs) by means of different experimental techniques. However, the structural determinants responsible for their different binding mode to the enzyme active site were not clearly defined so far. In this paper, we report the X-ray crystal structure of hCA II in complex with a sulphamate inhibitor incorporating a nitroimidazole moiety. The comparison with the structure of hCA II in complex with its sulphamide analogue revealed that the two inhibitors adopt a completely different binding mode within the hCA II active site. Starting from these results, we performed a theoretical study on sulphamate and sulphamide derivatives, demonstrating that electrostatic interactions with residues within the enzyme active site play a key role in determining their binding conformation. These findings open new perspectives in the design of effective CAIs using the sulphamate and sulphamide zinc binding groups as lead compounds.

Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator

NASA Astrophysics Data System (ADS)

Deng, Zengqin; Wang, Qing; Liu, Zhao; Zhang, Manfeng; Machado, Ana Carolina Dantas; Chiu, Tsu-Pei; Feng, Chong; Zhang, Qi; Yu, Lin; Qi, Lei; Zheng, Jiangge; Wang, Xu; Huo, Xinmei; Qi, Xiaoxuan; Li, Xiaorong; Wu, Wei; Rohs, Remo; Li, Ying; Chen, Zhongzhou

2015-07-01

Ferric uptake regulator (Fur) plays a key role in the iron homeostasis of prokaryotes, such as bacterial pathogens, but the molecular mechanisms and structural basis of Fur-DNA binding remain incompletely understood. Here, we report high-resolution structures of Magnetospirillum gryphiswaldense MSR-1 Fur in four different states: apo-Fur, holo-Fur, the Fur-feoAB1 operator complex and the Fur-Pseudomonas aeruginosa Fur box complex. Apo-Fur is a transition metal ion-independent dimer whose binding induces profound conformational changes and confers DNA-binding ability. Structural characterization, mutagenesis, biochemistry and in vivo data reveal that Fur recognizes DNA by using a combination of base readout through direct contacts in the major groove and shape readout through recognition of the minor-groove electrostatic potential by lysine. The resulting conformational plasticity enables Fur binding to diverse substrates. Our results provide insights into metal ion activation and substrate recognition by Fur that suggest pathways to engineer magnetotactic bacteria and antipathogenic drugs.

Structural Analysis of HMGD-DNA Complexes Reveal Influence of Intercalation on Sequence Selectivity and DNA Bending

PubMed Central

Churchill, Mair E.A.; Klass, Janet; Zoetewey, David L.

2010-01-01

The ubiquitous eukaryotic High-Mobility-Group-Box (HMGB) chromosomal proteins promote many chromatin-mediated cellular activities through their non-sequence-specific binding and bending of DNA. Minor groove DNA binding by the HMG box results in substantial DNA bending toward the major groove owing to electrostatic interactions, shape complementarity and DNA intercalation that occurs at two sites. Here, the structures of the complexes formed with DNA by a partially DNA intercalation-deficient mutant of Drosophila melanogaster HMGD have been determined by X-ray crystallography at a resolution of 2.85 Å. The six proteins and fifty base pairs of DNA in the crystal structure revealed a variety of bound conformations. All of the proteins bound in the minor groove, bridging DNA molecules, presumably because these DNA regions are easily deformed. The loss of the primary site of DNA intercalation decreased overall DNA bending and shape complementarity. However, DNA bending at the secondary site of intercalation was retained and most protein-DNA contacts were preserved. The mode of binding resembles the HMGB1-boxA-cisplatin-DNA complex, which also lacks a primary intercalating residue. This study provides new insights into the binding mechanisms used by HMG boxes to recognize varied DNA structures and sequences as well as modulate DNA structure and DNA bending. PMID:20800069

Optimal charges in lead progression: a structure-based neuraminidase case study.

PubMed

Armstrong, Kathryn A; Tidor, Bruce; Cheng, Alan C

2006-04-20

Collective experience in structure-based lead progression has found electrostatic interactions to be more difficult to optimize than shape-based ones. A major reason for this is that the net electrostatic contribution observed includes a significant nonintuitive desolvation component in addition to the more intuitive intermolecular interaction component. To investigate whether knowledge of the ligand optimal charge distribution can facilitate more intuitive design of electrostatic interactions, we took a series of small-molecule influenza neuraminidase inhibitors with known protein cocrystal structures and calculated the difference between the optimal and actual charge distributions. This difference from the electrostatic optimum correlates with the calculated electrostatic contribution to binding (r(2) = 0.94) despite small changes in binding modes caused by chemical substitutions, suggesting that the optimal charge distribution is a useful design goal. Furthermore, detailed suggestions for chemical modification generated by this approach are in many cases consistent with observed improvements in binding affinity, and the method appears to be useful despite discrete chemical constraints. Taken together, these results suggest that charge optimization is useful in facilitating generation of compound ideas in lead optimization. Our results also provide insight into design of neuraminidase inhibitors.

Architecture, Assembly, and Emerging Applications of Branched Functional Polyelectrolytes and Poly(ionic liquid)s.

PubMed

Xu, Weinan; Ledin, Petr A; Shevchenko, Valery V; Tsukruk, Vladimir V

2015-06-17

Branched polyelectrolytes with cylindrical brush, dendritic, hyperbranched, grafted, and star architectures bearing ionizable functional groups possess complex and unique assembly behavior in solution at surfaces and interfaces as compared to their linear counterparts. This review summarizes the recent developments in the introduction of various architectures and understanding of the assembly behavior of branched polyelectrolytes with a focus on functional polyelectrolytes and poly(ionic liquid)s with responsive properties. The branched polyelectrolytes and poly(ionic liquid)s interact electrostatically with small molecules, linear polyelectrolytes, or other branched polyelectrolytes to form assemblies of hybrid nanoparticles, multilayer thin films, responsive microcapsules, and ion-conductive membranes. The branched structures lead to unconventional assemblies and complex hierarchical structures with responsive properties as summarized in this review. Finally, we discuss prospectives for emerging applications of branched polyelectrolytes and poly(ionic liquid)s for energy harvesting and storage, controlled delivery, chemical microreactors, adaptive surfaces, and ion-exchange membranes.

3DRISM-HI-D2MSA: an improved analytic theory to compute solvent structure around hydrophobic solutes with proper treatment of solute–solvent electrostatic interactions

NASA Astrophysics Data System (ADS)

Cao, Siqin; Zhu, Lizhe; Huang, Xuhui

2018-04-01

The 3D reference interaction site model (3DRISM) is a powerful tool to study the thermodynamic and structural properties of liquids. However, for hydrophobic solutes, the inhomogeneity of the solvent density around them poses a great challenge to the 3DRISM theory. To address this issue, we have previously introduced the hydrophobic-induced density inhomogeneity theory (HI) for purely hydrophobic solutes. To further consider the complex hydrophobic solutes containing partial charges, here we propose the D2MSA closure to incorporate the short-range and long-range interactions with the D2 closure and the mean spherical approximation, respectively. We demonstrate that our new theory can compute the solvent distributions around real hydrophobic solutes in water and complex organic solvents that agree well with the explicit solvent molecular dynamics simulations.

Grid-based lattice summation of electrostatic potentials by assembled rank-structured tensor approximation

NASA Astrophysics Data System (ADS)

Khoromskaia, Venera; Khoromskij, Boris N.

2014-12-01

Our recent method for low-rank tensor representation of sums of the arbitrarily positioned electrostatic potentials discretized on a 3D Cartesian grid reduces the 3D tensor summation to operations involving only 1D vectors however retaining the linear complexity scaling in the number of potentials. Here, we introduce and study a novel tensor approach for fast and accurate assembled summation of a large number of lattice-allocated potentials represented on 3D N × N × N grid with the computational requirements only weakly dependent on the number of summed potentials. It is based on the assembled low-rank canonical tensor representations of the collected potentials using pointwise sums of shifted canonical vectors representing the single generating function, say the Newton kernel. For a sum of electrostatic potentials over L × L × L lattice embedded in a box the required storage scales linearly in the 1D grid-size, O(N) , while the numerical cost is estimated by O(NL) . For periodic boundary conditions, the storage demand remains proportional to the 1D grid-size of a unit cell, n = N / L, while the numerical cost reduces to O(N) , that outperforms the FFT-based Ewald-type summation algorithms of complexity O(N3 log N) . The complexity in the grid parameter N can be reduced even to the logarithmic scale O(log N) by using data-sparse representation of canonical N-vectors via the quantics tensor approximation. For justification, we prove an upper bound on the quantics ranks for the canonical vectors in the overall lattice sum. The presented approach is beneficial in applications which require further functional calculus with the lattice potential, say, scalar product with a function, integration or differentiation, which can be performed easily in tensor arithmetics on large 3D grids with 1D cost. Numerical tests illustrate the performance of the tensor summation method and confirm the estimated bounds on the tensor ranks.

Study on the shrinkage behavior and conductivity of silver microwires during electrostatic field assisted sintering

NASA Astrophysics Data System (ADS)

Shangguan, Lei; Ma, Liuhong; Li, Mengke; Peng, Wei; Zhong, Yinghui; Su, Yufeng; Duan, Zhiyong

2018-05-01

An electrostatic field was applied to sintering Ag microwires to achieve a more compact structure and better conductivity. The shrinkage behavior of Ag microwires shows anisotropy, since bigger particle sizes, less micropores and smoother surfaces were observed in the direction of the electrostatic field in comparsion with the direction perpendicular to the electrostatic field, and the shrinkage rate of Ag microwires in the direction of electrostatic field improves about 2.4% with the electrostatic field intensity of 800 V cm‑1. The electrostatic field assisted sintering model of Ag microwires is proposed according to thermal diffuse dynamics analysis and experimental research. Moreover, the grain size of Ag microwres sintered with electrostatic field increases with the electrostatic field intensity and reaches 113 nm when the electrostatic field intensity is 800 V cm‑1, and the resistivity decreases to 2.07  ×  10‑8 Ω m as well. This method may overcome the restriction of metal wires which fabricated by the pseudoplastic metal nanoparticle fluid and be used as interconnects in nanoimprint lithography.

Image charge models for accurate construction of the electrostatic self-energy of 3D layered nanostructure devices.

PubMed

Barker, John R; Martinez, Antonio

2018-04-04

Efficient analytical image charge models are derived for the full spatial variation of the electrostatic self-energy of electrons in semiconductor nanostructures that arises from dielectric mismatch using semi-classical analysis. The methodology provides a fast, compact and physically transparent computation for advanced device modeling. The underlying semi-classical model for the self-energy has been established and validated during recent years and depends on a slight modification of the macroscopic static dielectric constants for individual homogeneous dielectric regions. The model has been validated for point charges as close as one interatomic spacing to a sharp interface. A brief introduction to image charge methodology is followed by a discussion and demonstration of the traditional failure of the methodology to derive the electrostatic potential at arbitrary distances from a source charge. However, the self-energy involves the local limit of the difference between the electrostatic Green functions for the full dielectric heterostructure and the homogeneous equivalent. It is shown that high convergence may be achieved for the image charge method for this local limit. A simple re-normalisation technique is introduced to reduce the number of image terms to a minimum. A number of progressively complex 3D models are evaluated analytically and compared with high precision numerical computations. Accuracies of 1% are demonstrated. Introducing a simple technique for modeling the transition of the self-energy between disparate dielectric structures we generate an analytical model that describes the self-energy as a function of position within the source, drain and gated channel of a silicon wrap round gate field effect transistor on a scale of a few nanometers cross-section. At such scales the self-energies become large (typically up to ~100 meV) close to the interfaces as well as along the channel. The screening of a gated structure is shown to reduce the self-energy relative to un-gated nanowires.

Image charge models for accurate construction of the electrostatic self-energy of 3D layered nanostructure devices

NASA Astrophysics Data System (ADS)

Barker, John R.; Martinez, Antonio

2018-04-01

Efficient analytical image charge models are derived for the full spatial variation of the electrostatic self-energy of electrons in semiconductor nanostructures that arises from dielectric mismatch using semi-classical analysis. The methodology provides a fast, compact and physically transparent computation for advanced device modeling. The underlying semi-classical model for the self-energy has been established and validated during recent years and depends on a slight modification of the macroscopic static dielectric constants for individual homogeneous dielectric regions. The model has been validated for point charges as close as one interatomic spacing to a sharp interface. A brief introduction to image charge methodology is followed by a discussion and demonstration of the traditional failure of the methodology to derive the electrostatic potential at arbitrary distances from a source charge. However, the self-energy involves the local limit of the difference between the electrostatic Green functions for the full dielectric heterostructure and the homogeneous equivalent. It is shown that high convergence may be achieved for the image charge method for this local limit. A simple re-normalisation technique is introduced to reduce the number of image terms to a minimum. A number of progressively complex 3D models are evaluated analytically and compared with high precision numerical computations. Accuracies of 1% are demonstrated. Introducing a simple technique for modeling the transition of the self-energy between disparate dielectric structures we generate an analytical model that describes the self-energy as a function of position within the source, drain and gated channel of a silicon wrap round gate field effect transistor on a scale of a few nanometers cross-section. At such scales the self-energies become large (typically up to ~100 meV) close to the interfaces as well as along the channel. The screening of a gated structure is shown to reduce the self-energy relative to un-gated nanowires.

Electrostatic occlusion and quaternary structural ion pairing are key determinants of Cu(I)-mediated allostery in the copper-sensing operon repressor (CsoR).

PubMed

Chang, Feng-Ming James; Martin, Julia E; Giedroc, David P

2015-04-21

The copper-sensing operon repressor (CsoR) is an all-α-helical disc-shaped D2-symmetric homotetramer that forms a 2:1 tetramer/DNA operator complex and represses the expression of copper-resistance genes in a number of bacteria. A previous bioinformatics analysis of CsoR-family repressors distributes Cu(I)-sensing CsoRs in four of seven distinct clades on the basis of global sequence similarity. In this work, we define energetically important determinants of DNA binding in the apo-state (ΔΔGbind), and for allosteric negative coupling of Cu(I) binding to DNA binding (ΔΔGc) in a model clade IV CsoR from Geobacillus thermodenitrificans (Gt) of known structure, by selectively targeting for mutagenesis those charged residues uniquely conserved in clade IV CsoRs. These include a folded N-terminal "tail" and a number of Cu(I)-sensor and clade-specific residues that when mapped onto a model of Cu(I)-bound Gt CsoR define a path across one face of the tetramer. We find that Cu(I)-binding prevents formation of the 2:1 "sandwich" complex rather than DNA binding altogether. Folding of the N-terminal tail (residues R18, E22, R74) upon Cu-binding to the periphery of the tetramer inhibits assembly of the 2:1 apoprotein-DNA complex. In contrast, Ala substitution of residues that surround the central "hole" (R65, K101) in the tetramer, as well R48, impact DNA binding. We also identify a quaternary structural ion-pair, E73-K101″, that crosses the tetramer interface, charge-reversal of which restores DNA binding activity, allosteric regulation by Cu(I), and transcriptional derepression by Cu(I) in cells. These findings suggest an "electrostatic occlusion" model, in which basic residues important for DNA binding and/or allostery become sequestered via ion-pairing specifically in the Cu(I)-bound state, and this aids in copper-dependent disassembly of a repression complex.

Structural insights into the functions of the FANCM-FAAP24 complex in DNA repair

PubMed Central

Yang, Hui; Zhang, Tianlong; Tao, Ye; Wang, Fang; Tong, Liang; Ding, Jianping

2013-01-01

Fanconi anemia (FA) is a genetically heterogeneous disorder associated with deficiencies in the FA complementation group network. FA complementation group M (FANCM) and FA-associated protein 24 kDa (FAAP24) form a stable complex to anchor the FA core complex to chromatin in repairing DNA interstrand crosslinks. Here, we report the first crystal structure of the C-terminal segment of FANCM in complex with FAAP24. The C-terminal segment of FANCM and FAAP24 both consist of a nuclease domain at the N-terminus and a tandem helix-hairpin-helix (HhH)2 domain at the C-terminus. The FANCM-FAAP24 complex exhibits a similar architecture as that of ApXPF. However, the variations of several key residues and the electrostatic property at the active-site region render a catalytically inactive nuclease domain of FANCM, accounting for the lack of nuclease activity. We also show that the first HhH motif of FAAP24 is a potential binding site for DNA, which plays a critical role in targeting FANCM-FAAP24 to chromatin. These results reveal the mechanistic insights into the functions of FANCM-FAAP24 in DNA repair. PMID:24003026

Electrostatic adhesion for added functionality of composite structures

NASA Astrophysics Data System (ADS)

Heath, Callum J. C.; Bond, Ian P.; Potter, Kevin D.

2016-02-01

Electrostatic adhesion can be used as a means of reversible attachment. The incorporation of electrostatic adhesion into fibre reinforced polymer (FRP) composite structures could provide significant value added functionality. Imparting large potential differences (˜2 kV) across electrodes generates an attractive force, thus providing a means of attachment. This could be used as a reversible latching mechanism or as a means of controllable internal connectivity. Varying the connectivity for discrete elements of a substructure of a given design allows for control of internal load paths and moment of area of the cross section. This could facilitate variable stiffness (both in bending and torsion). Using a combination of existing fabrication techniques, functional electrodes have been integrated within a FRP. Copper polyimide thin film laminate material has been both co-cured with carbon fibre reinforced epoxy and bonded to PVC closed cell foam core material to provide a range of structural configurations with integrated electrodes. The ability of such integrated devices to confer variations in global bending stiffness of basic beam structures is investigated. Through the application of 4 kV across integrated electrostatic adhesive devices, a 112% increase in flexural stiffness has been demonstrated for a composite sandwich structure.

Nanoscale Origins of Ferroelastic Domain Wall Mobility in Ferroelectric Multilayers

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

Huang, Hsin-Hui; Hong, Zijian; Xin, Huolin L.

Here we investigate the nanoscale origins of ferroelastic domain wall motion in ferroelectric multilayer thin films that lead to giant electromechanical responses. We present direct evidence for complex underpinning factors that result in ferroelastic domain wall mobility using a combination of atomic-level aberration corrected scanning transmission electron microscopy and phase-field simulations in model epitaxial (001) tetragonal (T) PbZr xTi 1-xO 3 (PZT)/rhombohedral (R) PbZr xTi 1-xO 3 (PZT) bilayer heterostructures. The local electric dipole distribution is imaged on an atomic scale for a ferroelastic domain wall that nucleates in the R-layer and cuts through the composition breaking the T/R interface.more » Our studies reveal a highly complex polarization rotation domain structure that is nearly on the knife-edge at the vicinity of this wall. Induced phases, namely tetragonal-like and rhombohedral-like monoclinic were observed close to the interface, and exotic domain arrangements, such as a half-four-fold closure structure, are observed. Phase field simulations show this is due to the minimization of the excessive elastic and electrostatic energies driven by the enormous strain gradient present at the location of the ferroelastic domain walls. Thus, in response to an applied stimulus, such as an electric field, any polarization reorientation must minimize the elastic and electrostatic discontinuities due to this strain gradient, which would induce a dramatic rearrangement of the domain structure. This insight into the origins of ferroelastic domain wall motion will allow researchers to better “craft” such multilayered ferroelectric systems with precisely tailored domain wall functionality and enhanced sensitivity, which can be exploited for the next generation of integrated piezoelectric technologies.« less

Nanoscale Origins of Ferroelastic Domain Wall Mobility in Ferroelectric Multilayers

DOE PAGES

Huang, Hsin-Hui; Hong, Zijian; Xin, Huolin L.; ...

2016-10-31

Here we investigate the nanoscale origins of ferroelastic domain wall motion in ferroelectric multilayer thin films that lead to giant electromechanical responses. We present direct evidence for complex underpinning factors that result in ferroelastic domain wall mobility using a combination of atomic-level aberration corrected scanning transmission electron microscopy and phase-field simulations in model epitaxial (001) tetragonal (T) PbZr xTi 1-xO 3 (PZT)/rhombohedral (R) PbZr xTi 1-xO 3 (PZT) bilayer heterostructures. The local electric dipole distribution is imaged on an atomic scale for a ferroelastic domain wall that nucleates in the R-layer and cuts through the composition breaking the T/R interface.more » Our studies reveal a highly complex polarization rotation domain structure that is nearly on the knife-edge at the vicinity of this wall. Induced phases, namely tetragonal-like and rhombohedral-like monoclinic were observed close to the interface, and exotic domain arrangements, such as a half-four-fold closure structure, are observed. Phase field simulations show this is due to the minimization of the excessive elastic and electrostatic energies driven by the enormous strain gradient present at the location of the ferroelastic domain walls. Thus, in response to an applied stimulus, such as an electric field, any polarization reorientation must minimize the elastic and electrostatic discontinuities due to this strain gradient, which would induce a dramatic rearrangement of the domain structure. This insight into the origins of ferroelastic domain wall motion will allow researchers to better “craft” such multilayered ferroelectric systems with precisely tailored domain wall functionality and enhanced sensitivity, which can be exploited for the next generation of integrated piezoelectric technologies.« less

Extending Halogen-based Medicinal Chemistry to Proteins

PubMed Central

El Hage, Krystel; Pandyarajan, Vijay; Phillips, Nelson B.; Smith, Brian J.; Menting, John G.; Whittaker, Jonathan; Lawrence, Michael C.; Meuwly, Markus; Weiss, Michael A.

2016-01-01

Insulin, a protein critical for metabolic homeostasis, provides a classical model for protein design with application to human health. Recent efforts to improve its pharmaceutical formulation demonstrated that iodination of a conserved tyrosine (TyrB26) enhances key properties of a rapid-acting clinical analog. Moreover, the broad utility of halogens in medicinal chemistry has motivated the use of hybrid quantum- and molecular-mechanical methods to study proteins. Here, we (i) undertook quantitative atomistic simulations of 3-[iodo-TyrB26]insulin to predict its structural features, and (ii) tested these predictions by X-ray crystallography. Using an electrostatic model of the modified aromatic ring based on quantum chemistry, the calculations suggested that the analog, as a dimer and hexamer, exhibits subtle differences in aromatic-aromatic interactions at the dimer interface. Aromatic rings (TyrB16, PheB24, PheB25, 3-I-TyrB26, and their symmetry-related mates) at this interface adjust to enable packing of the hydrophobic iodine atoms within the core of each monomer. Strikingly, these features were observed in the crystal structure of a 3-[iodo-TyrB26]insulin analog (determined as an R6 zinc hexamer). Given that residues B24–B30 detach from the core on receptor binding, the environment of 3-I-TyrB26 in a receptor complex must differ from that in the free hormone. Based on the recent structure of a “micro-receptor” complex, we predict that 3-I-TyrB26 engages the receptor via directional halogen bonding and halogen-directed hydrogen bonding as follows: favorable electrostatic interactions exploiting, respectively, the halogen's electron-deficient σ-hole and electronegative equatorial band. Inspired by quantum chemistry and molecular dynamics, such “halogen engineering” promises to extend principles of medicinal chemistry to proteins. PMID:27875310

Electrostatic potential of B-DNA: effect of interionic correlations.

PubMed Central

Gavryushov, S; Zielenkiewicz, P

1998-01-01

Modified Poisson-Boltzmann (MPB) equations have been numerically solved to study ionic distributions and mean electrostatic potentials around a macromolecule of arbitrarily complex shape and charge distribution. Results for DNA are compared with those obtained by classical Poisson-Boltzmann (PB) calculations. The comparisons were made for 1:1 and 2:1 electrolytes at ionic strengths up to 1 M. It is found that ion-image charge interactions and interionic correlations, which are neglected by the PB equation, have relatively weak effects on the electrostatic potential at charged groups of the DNA. The PB equation predicts errors in the long-range electrostatic part of the free energy that are only approximately 1.5 kJ/mol per nucleotide even in the case of an asymmetrical electrolyte. In contrast, the spatial correlations between ions drastically affect the electrostatic potential at significant separations from the macromolecule leading to a clearly predicted effect of charge overneutralization. PMID:9826596

Predicting Electrostatic Forces in RNA Folding

PubMed Central

Tan, Zhi-Jie; Chen, Shi-Jie

2016-01-01

Metal ion-mediated electrostatic interactions are critical to RNA folding. Although considerable progress has been made in mechanistic studies, the problem of accurate predictions for the ion effects in RNA folding remains unsolved, mainly due to the complexity of several potentially important issues such as ion correlation and dehydration effects. In this chapter, after giving a brief overview of the experimental findings and theoretical approaches, we focus on a recently developed new model, the tightly bound ion (TBI) model, for ion electrostatics in RNA folding. The model is unique because it can treat ion correlation and fluctuation effects for realistic RNA 3D structures. For monovalent ion (such as Na+) solutions, where ion correlation is weak, TBI and the Poisson–Boltzmann (PB) theory give the same results and the results agree with the experimental data. For multivalent ion (such as Mg2+) solutions, where ion correlation can be strong, however, TBI gives much improved predictions than the PB. Moreover, the model suggests an ion correlation- induced mechanism for the unusual efficiency of Mg2+ ions in the stabilization of RNA tertiary folds. In this chapter, after introducing the theoretical framework of the TBI model, we will describe how to apply the model to predict ion-binding properties and ion-dependent folding stabilities. PMID:20946803

Electrostatic Model Applied to ISS Charged Water Droplet Experiment

NASA Technical Reports Server (NTRS)

Stevenson, Daan; Schaub, Hanspeter; Pettit, Donald R.

2015-01-01

The electrostatic force can be used to create novel relative motion between charged bodies if it can be isolated from the stronger gravitational and dissipative forces. Recently, Coulomb orbital motion was demonstrated on the International Space Station by releasing charged water droplets in the vicinity of a charged knitting needle. In this investigation, the Multi-Sphere Method, an electrostatic model developed to study active spacecraft position control by Coulomb charging, is used to simulate the complex orbital motion of the droplets. When atmospheric drag is introduced, the simulated motion closely mimics that seen in the video footage of the experiment. The electrostatic force's inverse dependency on separation distance near the center of the needle lends itself to analytic predictions of the radial motion.

Structural studies of p53 inactivation by DNA-contact mutations and its rescue by suppressor mutations via alternative protein–DNA interactions

PubMed Central

Eldar, Amir; Rozenberg, Haim; Diskin-Posner, Yael; Rohs, Remo; Shakked, Zippora

2013-01-01

A p53 hot-spot mutation found frequently in human cancer is the replacement of R273 by histidine or cysteine residues resulting in p53 loss of function as a tumor suppressor. These mutants can be reactivated by the incorporation of second-site suppressor mutations. Here, we present high-resolution crystal structures of the p53 core domains of the cancer-related proteins, the rescued proteins and their complexes with DNA. The structures show that inactivation of p53 results from the incapacity of the mutated residues to form stabilizing interactions with the DNA backbone, and that reactivation is achieved through alternative interactions formed by the suppressor mutations. Detailed structural and computational analysis demonstrates that the rescued p53 complexes are not fully restored in terms of DNA structure and its interface with p53. Contrary to our previously studied wild-type (wt) p53-DNA complexes showing non-canonical Hoogsteen A/T base pairs of the DNA helix that lead to local minor-groove narrowing and enhanced electrostatic interactions with p53, the current structures display Watson–Crick base pairs associated with direct or water-mediated hydrogen bonds with p53 at the minor groove. These findings highlight the pivotal role played by R273 residues in supporting the unique geometry of the DNA target and its sequence-specific complex with p53. PMID:23863845

Hydrogen bonding interactions in PN...HX complexes: DFT and ab initio studies of structure, properties and topology.

PubMed

Varadwaj, Pradeep Risikrishna

2010-05-01

Spin-restricted DFT (X3LYP and B3LYP) and ab initio (MP2(fc) and CCSD(fc)) calculations in conjunction with the Aug-CC-pVDZ and Aug-CC-pVTZ basis sets were performed on a series of hydrogen bonded complexes PN...HX (X = F, Cl, Br) to examine the variations of their equilibrium gas phase structures, energetic stabilities, electronic properties, and vibrational characteristics in their electronic ground states. In all cases the complexes were predicted to be stable with respect to the constituent monomers. The interaction energy (Delta E) calculated using a super-molecular model is found to be in this order: PN...HF > PN...HCl > PN...HBr in the series examined. Analysis of various physically meaningful contributions arising from the Kitaura-Morokuma (KM) and reduced variational space self-consistent-field (RVS-SCF) energy decomposition procedures shows that the electrostatic energy has significant contribution to the over-all interaction energy. Dipole moment enhancement (Delta mu) was observed in these complexes expected of predominant dipole-dipole electrostatic interaction and was found to follow the trend PN...HF > PN...HCl > PN...HBr at the CCSD level. However, the DFT (X3LYP and B3LYP) and MP2 levels less accurately determined these values (in this order HF < HCl < HBr). Examination of the harmonic vibrational modes reveals that the PN and HX bands exhibit characteristic blue- and red shifts with concomitant bond contraction and elongation, respectively, on hydrogen bond formation. The topological or critical point (CP) analysis using the static quantum theory of atoms in molecules (QTAIM) of Bader was considered to classify and to gain further insight into the nature of interaction existing in the monomers PN and HX, and between them on H-bond formation. It is found from the analysis of the electron density rho ( c ), the Laplacian of electron charge density nabla(2)rho(c), and the total energy density (H ( c )) at the critical points between the interatomic regions that the interaction N...H is indeed electrostatic in origin (rho(c) > 0, nabla(2)rho(c) > 0 and H(c) > 0 at the BCP) whilst the bonds in PN (rho(c) > 0, nabla(2)rho(c) > 0 and H(c) < 0) and HX ((rho(c) > 0, nabla(2)rho(c) < 0 and H(c) < 0)) are predominantly covalent. A natural bond orbital (NBO) analysis of the second order perturbation energy lowering, E((2)), caused by charge transfer mechanism shows that the interaction N...H is n(N) --> BD*(HX) delocalization.

The active site of hydroxynitrile lyase from Prunus amygdalus: Modeling studies provide new insights into the mechanism of cyanogenesis

PubMed Central

Dreveny, Ingrid; Kratky, Christoph; Gruber, Karl

2002-01-01

The FAD-dependent hydroxynitrile lyase from almond (Prunus amygdalus, PaHNL) catalyzes the cleavage of R-mandelonitrile into benzaldehyde and hydrocyanic acid. Catalysis of the reverse reaction—the enantiospecific formation of α-hydroxynitriles—is now widely utilized in organic syntheses as one of the few industrially relevant examples of enzyme-mediated C–C bond formation. Starting from the recently determined X-ray crystal structure, systematic docking calculations with the natural substrate were used to locate the active site of the enzyme and to identify amino acid residues involved in substrate binding and catalysis. Analysis of the modeled substrate complexes supports an enzymatic mechanism that includes the flavin cofactor as a mere "spectator" of the reaction and relies on general acid/base catalysis by the conserved His-497. Stabilization of the negative charge of the cyanide ion is accomplished by a pronounced positive electrostatic potential at the binding site. PaHNL activity requires the FAD cofactor to be bound in its oxidized form, and calculations of the pKa of enzyme-bound HCN showed that the observed inactivation upon cofactor reduction is largely caused by the reversal of the electrostatic potential within the active site. The suggested mechanism closely resembles the one proposed for the FAD-independent, and structurally unrelated HNL from Hevea brasiliensis. Although the actual amino acid residues involved in the catalytic cycle are completely different in the two enzymes, a common motif for the mechanism of cyanogenesis (general acid/base catalysis plus electrostatic stabilization of the cyanide ion) becomes evident. PMID:11790839

The Kaposi Sarcoma Herpesvirus Latency-associated Nuclear Antigen DNA Binding Domain Dorsal Positive Electrostatic Patch Facilitates DNA Replication and Episome Persistence*

PubMed Central

Li, Shijun; Tan, Min; Juillard, Franceline; Ponnusamy, Rajesh; Correia, Bruno; Simas, J. Pedro; Carrondo, Maria A.; McVey, Colin E.; Kaye, Kenneth M.

2015-01-01

Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA binding surface, which is the site of BET protein binding. Here we investigate the functional role of the positive patch in LANA-mediated episome persistence. As expected, LANA mutants with alanine or glutamate substitutions in the central, peripheral, or lateral portions of the positive patch maintained the ability to bind DNA by EMSA. However, all of the substitution mutants were deficient for LANA DNA replication and episome maintenance. Mutation of the peripheral region generated the largest deficiencies. Despite these deficiencies, all positive patch mutants concentrated to dots along mitotic chromosomes in cells containing episomes, similar to LANA. The central and peripheral mutants, but not the lateral mutants, were reduced for BET protein interaction as assessed by co-immunoprecipitation. However, defects in BET protein binding were independent of episome maintenance function. Overall, the reductions in episome maintenance closely correlated with DNA replication deficiencies, suggesting that the replication defects account for the reduced episome persistence. Therefore, the electrostatic patch exerts a key role in LANA-mediated DNA replication and episome persistence and may act through a host cell partner(s) other than a BET protein or by inducing specific structures or complexes. PMID:26420481

Very compact, high-stability electrostatic actuator featuring contact-free self-limiting displacement

DOEpatents

Rodgers, M. Steven; Miller, Samuel L.

2003-01-01

A compact electrostatic actuator is disclosed for microelectromechanical (MEM) applications. The actuator utilizes stationary and moveable electrodes, with the stationary electrodes being formed on a substrate and the moveable electrodes being supported above the substrate on a frame. The frame provides a rigid structure which allows the electrostatic actuator to be operated at high voltages (up to 190 Volts) to provide a relatively large actuation force compared to conventional electrostatic comb actuators which are much larger in size. For operation at its maximum displacement, the electrostatic actuator is relatively insensitive to the exact value of the applied voltage and provides a self-limiting displacement.

Molecular recognition in a diverse set of protein-ligand interactions studied with molecular dynamics simulations and end-point free energy calculations.

PubMed

Wang, Bo; Li, Liwei; Hurley, Thomas D; Meroueh, Samy O

2013-10-28

End-point free energy calculations using MM-GBSA and MM-PBSA provide a detailed understanding of molecular recognition in protein-ligand interactions. The binding free energy can be used to rank-order protein-ligand structures in virtual screening for compound or target identification. Here, we carry out free energy calculations for a diverse set of 11 proteins bound to 14 small molecules using extensive explicit-solvent MD simulations. The structure of these complexes was previously solved by crystallography and their binding studied with isothermal titration calorimetry (ITC) data enabling direct comparison to the MM-GBSA and MM-PBSA calculations. Four MM-GBSA and three MM-PBSA calculations reproduced the ITC free energy within 1 kcal·mol(-1) highlighting the challenges in reproducing the absolute free energy from end-point free energy calculations. MM-GBSA exhibited better rank-ordering with a Spearman ρ of 0.68 compared to 0.40 for MM-PBSA with dielectric constant (ε = 1). An increase in ε resulted in significantly better rank-ordering for MM-PBSA (ρ = 0.91 for ε = 10), but larger ε significantly reduced the contributions of electrostatics, suggesting that the improvement is due to the nonpolar and entropy components, rather than a better representation of the electrostatics. The SVRKB scoring function applied to MD snapshots resulted in excellent rank-ordering (ρ = 0.81). Calculations of the configurational entropy using normal-mode analysis led to free energies that correlated significantly better to the ITC free energy than the MD-based quasi-harmonic approach, but the computed entropies showed no correlation with the ITC entropy. When the adaptation energy is taken into consideration by running separate simulations for complex, apo, and ligand (MM-PBSAADAPT), there is less agreement with the ITC data for the individual free energies, but remarkably good rank-ordering is observed (ρ = 0.89). Interestingly, filtering MD snapshots by prescoring protein-ligand complexes with a machine learning-based approach (SVMSP) resulted in a significant improvement in the MM-PBSA results (ε = 1) from ρ = 0.40 to ρ = 0.81. Finally, the nonpolar components of MM-GBSA and MM-PBSA, but not the electrostatic components, showed strong correlation to the ITC free energy; the computed entropies did not correlate with the ITC entropy.

Molecular Recognition in a Diverse Set of Protein-Ligand Interactions Studied with Molecular Dynamics Simulations and End-Point Free Energy Calculations

PubMed Central

Wang, Bo; Li, Liwei; Hurley, Thomas D.; Meroueh, Samy O.

2014-01-01

End-point free energy calculations using MM-GBSA and MM-PBSA provide a detailed understanding of molecular recognition in protein-ligand interactions. The binding free energy can be used to rank-order protein-ligand structures in virtual screening for compound or target identification. Here, we carry out free energy calculations for a diverse set of 11 proteins bound to 14 small molecules using extensive explicit-solvent MD simulations. The structure of these complexes was previously solved by crystallography and their binding studied with isothermal titration calorimetry (ITC) data enabling direct comparison to the MM-GBSA and MM-PBSA calculations. Four MM-GBSA and three MM-PBSA calculations reproduced the ITC free energy within 1 kcal•mol−1 highlighting the challenges in reproducing the absolute free energy from end-point free energy calculations. MM-GBSA exhibited better rank-ordering with a Spearman ρ of 0.68 compared to 0.40 for MM-PBSA with dielectric constant (ε = 1). An increase in ε resulted in significantly better rank-ordering for MM-PBSA (ρ = 0.91 for ε = 10). But larger ε significantly reduced the contributions of electrostatics, suggesting that the improvement is due to the non-polar and entropy components, rather than a better representation of the electrostatics. SVRKB scoring function applied to MD snapshots resulted in excellent rank-ordering (ρ = 0.81). Calculations of the configurational entropy using normal mode analysis led to free energies that correlated significantly better to the ITC free energy than the MD-based quasi-harmonic approach, but the computed entropies showed no correlation with the ITC entropy. When the adaptation energy is taken into consideration by running separate simulations for complex, apo and ligand (MM-PBSAADAPT), there is less agreement with the ITC data for the individual free energies, but remarkably good rank-ordering is observed (ρ = 0.89). Interestingly, filtering MD snapshots by pre-scoring protein-ligand complexes with a machine learning-based approach (SVMSP) resulted in a significant improvement in the MM-PBSA results (ε = 1) from ρ = 0.40 to ρ = 0.81. Finally, the non-polar components of MM-GBSA and MM-PBSA, but not the electrostatic components, showed strong correlation to the ITC free energy; the computed entropies did not correlate with the ITC entropy. PMID:24032517

A Triboelectric Sensor Array for Electrostatic Studies on the Lunar Surface

NASA Technical Reports Server (NTRS)

Johansen, Michael R.; Mackey, Paul J.; Calle, C. I.

2015-01-01

The moons electrostatic environment requires careful consideration in the development of future lunar landers. Electrostatically charged dust was well documented during the Apollo missions to cause thermal control, mechanical, and visibility issues. The fine dust particles that make up the surface are electrostatically charged as a result of numerous charging mechanisms. The relatively dry conditions on the moon creates a prime tribocharging environment during surface operations. The photoelectric effect is dominant for lunar day static charging, while plasma electrons are the main contributor for lunar night electrostatic effects. Electrostatic charging is also dependent on solar intensity, Earth-moon relative positions, and cosmic ray flux. This leads to a very complex and dynamic electrostatic environment that must be studied for the success of long term lunar missions.In order to better understand the electrostatic environment of planetary bodies, Kennedy Space Center, in previous collaboration with the Jet Propulsion Laboratory, has developed an electrostatic sensor suite. One of the instruments included in this package is the triboelectric sensor array. It is comprised of strategically selected materials that span the triboelectric series and that also have previous spaceflight history. In this presentation, we discuss detailed testing with the triboelectric sensor array performed at Kennedy Space Center. We will discuss potential benefits and use cases of this low mass, low cost sensor package, both for science and for mission success.

Structure of the carboxypeptidase B complex with N-sulfamoyl-L-phenylalanine - a transition state analog of non-specific substrate.

PubMed

Akparov, Valery; Timofeev, Vladimir; Khaliullin, Ilyas; Švedas, Vytas; Kuranova, Inna

2018-03-01

Carboxypeptidase B (EC 3.4.17.2) (CPB) is commonly used in the industrial insulin production and as a template for drug design. However, its ability to discriminate substrates with hydrophobic, hydrophilic, and charged side chains is not well understood. We report structure of CPB complex with a transition state analog N-sulfamoyl-L-phenylalanine solved at 1.74Å. The study provided an insight into structural basis of CPB substrate specificity. Ligand binding is affected by structure-depended conformational changes of Asp255 in S1'-subsite, interactions with Asn144 and Arg145 in C-terminal binding subsite, and Glu270 in the catalytic center. Side chain of the non-specific substrate analog SPhe in comparison with that of specific substrate analog SArg (reported earlier) not only loses favorable electrostatic interactions and two hydrogen bonds with Asp255 and three fixed water molecules, but is forced to be in the unfavorable hydrophilic environment. Thus, Ser207, Gly253, Tyr248, and Asp255 residues play major role in the substrate recognition by S1'-subsite.

[Energetics of complex formation of the DNA hairpin structure d(GCGAAGC) with aromatic ligands].

PubMed

Kostiukov, V V

2011-01-01

The energy contributions of various physical interactions to the total Gibbs energy of complex formation of the biologically important DNA hairpin d(GCGAAGC) with aromatic antitumor antibiotics daunomycin and novantron and the mutagens ethidium and proflavine have been calculated. It has been shown that the relatively small value of the total energy of binding of the ligands to the hairpin is the sum of components great in absolute value and different in sign. The contributions of van der Waals interactions and both intra- and intermolecular hydrogen bonds and bonds with aqueous environment have been studied. According to the calculations, the hydrophobic and van der Waals components are energetically favorable in complex formation of the ligands with the DNA pairpin d(GCGAAGC), whereas the electrostatic (with consideration of hydrogen bonds) and entropic components are unfavorable.

Material Science Smart Coatings

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

Rubinstein, A. I.; Sabirianov, R. F.; Namavar, Fereydoon

2014-07-01

The contribution of electrostatic interactions to the free energy of binding between model protein and a ceramic implant surface in the aqueous solvent, considered in the framework of the nonlocal electrostatic model, is calculated as a function of the implant low-frequency dielectric constant. We show that the existence of a dynamically ordered (low-dielectric) interfacial solvent layer at the protein-solvent and ceramic-solvent interface markedly increases charging energy of the protein and ceramic implant, and consequently makes the electrostatic contribution to the protein-ceramic binding energy more favorable (attractive). Our analysis shows that the corresponding electrostatic energy between protein and oxide ceramics dependsmore » nonmonotonically on the dielectric constant of ceramic, ε C. Obtained results indicate that protein can attract electrostatically to the surface if ceramic material has a moderate ε C below or about 35 (in particularly ZrO 2 or Ta 2O 5). This is in contrast to classical (local) consideration of the solvent, which demonstrates an unfavorable electrostatic interaction of protein with typical metal oxide ceramic materials (ε C>10). Thus, a solid implant coated by combining oxide ceramic with a reduced dielectric constant can be beneficial to strengthen the electrostatic binding of the protein-implant complex.« less

Quantum mechanical fragment methods based on partitioning atoms or partitioning coordinates.

PubMed

Wang, Bo; Yang, Ke R; Xu, Xuefei; Isegawa, Miho; Leverentz, Hannah R; Truhlar, Donald G

2014-09-16

Conspectus The development of more efficient and more accurate ways to represent reactive potential energy surfaces is a requirement for extending the simulation of large systems to more complex systems, longer-time dynamical processes, and more complete statistical mechanical sampling. One way to treat large systems is by direct dynamics fragment methods. Another way is by fitting system-specific analytic potential energy functions with methods adapted to large systems. Here we consider both approaches. First we consider three fragment methods that allow a given monomer to appear in more than one fragment. The first two approaches are the electrostatically embedded many-body (EE-MB) expansion and the electrostatically embedded many-body expansion of the correlation energy (EE-MB-CE), which we have shown to yield quite accurate results even when one restricts the calculations to include only electrostatically embedded dimers. The third fragment method is the electrostatically embedded molecular tailoring approach (EE-MTA), which is more flexible than EE-MB and EE-MB-CE. We show that electrostatic embedding greatly improves the accuracy of these approaches compared with the original unembedded approaches. Quantum mechanical fragment methods share with combined quantum mechanical/molecular mechanical (QM/MM) methods the need to treat a quantum mechanical fragment in the presence of the rest of the system, which is especially challenging for those parts of the rest of the system that are close to the boundary of the quantum mechanical fragment. This is a delicate matter even for fragments that are not covalently bonded to the rest of the system, but it becomes even more difficult when the boundary of the quantum mechanical fragment cuts a bond. We have developed a suite of methods for more realistically treating interactions across such boundaries. These methods include redistributing and balancing the external partial atomic charges and the use of tuned fluorine atoms for capping dangling bonds, and we have shown that they can greatly improve the accuracy. Finally we present a new approach that goes beyond QM/MM by combining the convenience of molecular mechanics with the accuracy of fitting a potential function to electronic structure calculations on a specific system. To make the latter practical for systems with a large number of degrees of freedom, we developed a method to interpolate between local internal-coordinate fits to the potential energy. A key issue for the application to large systems is that rather than assigning the atoms or monomers to fragments, we assign the internal coordinates to reaction, secondary, and tertiary sets. Thus, we make a partition in coordinate space rather than atom space. Fits to the local dependence of the potential energy on tertiary coordinates are arrayed along a preselected reaction coordinate at a sequence of geometries called anchor points; the potential energy function is called an anchor points reactive potential. Electrostatically embedded fragment methods and the anchor points reactive potential, because they are based on treating an entire system by quantum mechanical electronic structure methods but are affordable for large and complex systems, have the potential to open new areas for accurate simulations where combined QM/MM methods are inadequate.

A computational study of the chemokine receptor CXCR1 bound with interleukin-8

NASA Astrophysics Data System (ADS)

Wang, Yang; Severin Lupala, Cecylia; Wang, Ting; Li, Xuanxuan; Yun, Ji-Hye; Park, Jae-hyun; Jin, Zeyu; Lee, Weontae; Tan, Leihan; Liu, Haiguang

2018-03-01

CXCR1 is a G-protein coupled receptor, transducing signals from chemokines, in particular the interleukin-8 (IL8) molecules. This study combines homology modeling and molecular dynamics simulation methods to study the structure of CXCR1-IL8 complex. By using CXCR4-vMIP-II crystallography structure as the homologous template, CXCR1-IL8 complex structure was constructed, and then refined using all-atom molecular dynamics simulations. Through extensive simulations, CXCR1-IL8 binding poses were investigated in detail. Furthermore, the role of the N-terminal of CXCR1 receptor was studied by comparing four complex models differing in the N-terminal sequences. The results indicate that the receptor N-terminal affects the binding of IL8 significantly. With a shorter N-terminal domain, the binding of IL8 to CXCR1 becomes unstable. The homology modeling and simulations also reveal the key receptor-ligand residues involved in the electrostatic interactions known to be vital for complex formation. Project supported by the National Natural Science Foundation of China (Grant Nos. 11575021, U1530401, and U1430237) and the National Research Foundation of Korea (Grant Nos. NRF-2017R1A2B2008483 and NRF-2016R1A6A3A04010213).

Correlating Nitrile IR Frequencies to Local Electrostatics Quantifies Noncovalent Interactions of Peptides and Proteins.

PubMed

Deb, Pranab; Haldar, Tapas; Kashid, Somnath M; Banerjee, Subhrashis; Chakrabarty, Suman; Bagchi, Sayan

2016-05-05

Noncovalent interactions, in particular the hydrogen bonds and nonspecific long-range electrostatic interactions are fundamental to biomolecular functions. A molecular understanding of the local electrostatic environment, consistently for both specific (hydrogen-bonding) and nonspecific electrostatic (local polarity) interactions, is essential for a detailed understanding of these processes. Vibrational Stark Effect (VSE) has proven to be an extremely useful method to measure the local electric field using infrared spectroscopy of carbonyl and nitrile based probes. The nitrile chemical group would be an ideal choice because of its absorption in an infrared spectral window transparent to biomolecules, ease of site-specific incorporation into proteins, and common occurrence as a substituent in various drug molecules. However, the inability of VSE to describe the dependence of IR frequency on electric field for hydrogen-bonded nitriles to date has severely limited nitrile's utility to probe the noncovalent interactions. In this work, using infrared spectroscopy and atomistic molecular dynamics simulations, we have reported for the first time a linear correlation between nitrile frequencies and electric fields in a wide range of hydrogen-bonding environments that may bridge the existing gap between VSE and H-bonding interactions. We have demonstrated the robustness of this field-frequency correlation for both aromatic nitriles and sulfur-based nitriles in a wide range of molecules of varying size and compactness, including small molecules in complex solvation environments, an amino acid, disordered peptides, and structured proteins. This correlation, when coupled to VSE, can be used to quantify noncovalent interactions, specific or nonspecific, in a consistent manner.

Vlasov Simulation of Electrostatic Solitary Structures in Multi-Component Plasmas

NASA Technical Reports Server (NTRS)

Umeda, Takayuki; Ashour-Abdalla, Maha; Pickett, Jolene S.; Goldstein, Melvyn L.

2012-01-01

Electrostatic solitary structures have been observed in the Earth's magnetosheath by the Cluster spacecraft. Recent theoretical work has suggested that these solitary structures are modeled by electron acoustic solitary waves existing in a four-component plasma system consisting of core electrons, two counter-streaming electron beams, and one species of background ions. In this paper, the excitation of electron acoustic waves and the formation of solitary structures are studied by means of a one-dimensional electrostatic Vlasov simulation. The present result first shows that either electron acoustic solitary waves with negative potential or electron phase-space holes with positive potential are excited in four-component plasma systems. However, these electrostatic solitary structures have longer duration times and higher wave amplitudes than the solitary structures observed in the magnetosheath. The result indicates that a high-speed and small free energy source may be needed as a fifth component. An additional simulation of a five-component plasma consisting of a stable four-component plasma and a weak electron beam shows the generation of small and fast electron phase-space holes by the bump-on-tail instability. The physical properties of the small and fast electron phase-space holes are very similar to those obtained by the previous theoretical analysis. The amplitude and duration time of solitary structures in the simulation are also in agreement with the Cluster observation.

Protein Frustratometer 2: a tool to localize energetic frustration in protein molecules, now with electrostatics.

PubMed

Parra, R Gonzalo; Schafer, Nicholas P; Radusky, Leandro G; Tsai, Min-Yeh; Guzovsky, A Brenda; Wolynes, Peter G; Ferreiro, Diego U

2016-07-08

The protein frustratometer is an energy landscape theory-inspired algorithm that aims at localizing and quantifying the energetic frustration present in protein molecules. Frustration is a useful concept for analyzing proteins' biological behavior. It compares the energy distributions of the native state with respect to structural decoys. The network of minimally frustrated interactions encompasses the folding core of the molecule. Sites of high local frustration often correlate with functional regions such as binding sites and regions involved in allosteric transitions. We present here an upgraded version of a webserver that measures local frustration. The new implementation that allows the inclusion of electrostatic energy terms, important to the interactions with nucleic acids, is significantly faster than the previous version enabling the analysis of large macromolecular complexes within a user-friendly interface. The webserver is freely available at URL: http://frustratometer.qb.fcen.uba.ar. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Structure-based prediction of free energy changes of binding of PTP1B inhibitors

NASA Astrophysics Data System (ADS)

Wang, Jing; Ling Chan, Shek; Ramnarayan, Kal

2003-08-01

The goals were (1) to understand the driving forces in the binding of small molecule inhibitors to the active site of PTP1B and (2) to develop a molecular mechanics-based empirical free energy function for compound potency prediction. A set of compounds with known activities was docked onto the active site. The related energy components and molecular surface areas were calculated. The bridging water molecules were identified and their contributions were considered. Linear relationships were explored between the above terms and the binding free energies of compounds derived based on experimental inhibition constants. We found that minimally three terms are required to give rise to a good correlation (0.86) with predictive power in five-group cross-validation test (q2 = 0.70). The dominant terms are the electrostatic energy and non-electrostatic energy stemming from the intra- and intermolecular interactions of solutes and from those of bridging water molecules in complexes.

Formation of Polyelectrolyte Complex Colloid Particles between Chitosan and Pectin with Different Degree of Esterification

NASA Astrophysics Data System (ADS)

Wang, Hui; Sun, Hongyuan; He, Jieyu

2017-12-01

The effects of degree of esterification, pectin/chitosan ratio and pH on the formation of polyelectrolyte complex colloid particles between chitosan (CS) and pectin (PE) were investigated. Low methoxyl pectin (LPE) was achieved by de-esterifying high methoxyl pectin (HPE) with pectin methyl esterase. Turbidity titration and colorimetric method was used to determine the stability of complex colloid particles. The structure and morphology of complex particles were characterized by FTIR and TEM. When pectin solution was dropped into chitosan solution, complex colloidal dispersion was stable as PE/CS mass ratio was no more than 3:2. Colloidal particles of HPE-CS complex coagulated at larger ratio of PE/CS than LPE-CS. The maximum complex occurred at pH 6.1 for HPE-CS and pH 5.7 for LPE-CS, and decreasing pH leaded to the dissociation of complex particles. Electrostatic interactions between carboxyl groups on pectin and amino groups on chitosan were confirmed by FTIR. Colloidal particle sizes ranged from about 100 nm to 400 nm with spherical shape.

S/G-1: an ab initio force-field blending frozen Hermite Gaussian densities and distributed multipoles. Proof of concept and first applications to metal cations.

PubMed

Chaudret, Robin; Gresh, Nohad; Narth, Christophe; Lagardère, Louis; Darden, Thomas A; Cisneros, G Andrés; Piquemal, Jean-Philip

2014-09-04

We demonstrate as a proof of principle the capabilities of a novel hybrid MM'/MM polarizable force field to integrate short-range quantum effects in molecular mechanics (MM) through the use of Gaussian electrostatics. This lead to a further gain in accuracy in the representation of the first coordination shell of metal ions. It uses advanced electrostatics and couples two point dipole polarizable force fields, namely, the Gaussian electrostatic model (GEM), a model based on density fitting, which uses fitted electronic densities to evaluate nonbonded interactions, and SIBFA (sum of interactions between fragments ab initio computed), which resorts to distributed multipoles. To understand the benefits of the use of Gaussian electrostatics, we evaluate first the accuracy of GEM, which is a pure density-based Gaussian electrostatics model on a test Ca(II)-H2O complex. GEM is shown to further improve the agreement of MM polarization with ab initio reference results. Indeed, GEM introduces nonclassical effects by modeling the short-range quantum behavior of electric fields and therefore enables a straightforward (and selective) inclusion of the sole overlap-dependent exchange-polarization repulsive contribution by means of a Gaussian damping function acting on the GEM fields. The S/G-1 scheme is then introduced. Upon limiting the use of Gaussian electrostatics to metal centers only, it is shown to be able to capture the dominant quantum effects at play on the metal coordination sphere. S/G-1 is able to accurately reproduce ab initio total interaction energies within closed-shell metal complexes regarding each individual contribution including the separate contributions of induction, polarization, and charge-transfer. Applications of the method are provided for various systems including the HIV-1 NCp7-Zn(II) metalloprotein. S/G-1 is then extended to heavy metal complexes. Tested on Hg(II) water complexes, S/G-1 is shown to accurately model polarization up to quadrupolar response level. This opens up the possibility of embodying explicit scalar relativistic effects in molecular mechanics thanks to the direct transferability of ab initio pseudopotentials. Therefore, incorporating GEM-like electron density for a metal cation enable the introduction of nonambiguous short-range quantum effects within any point-dipole based polarizable force field without the need of an extensive parametrization.

Complex fluids with mobile charge-regulating macro-ions

NASA Astrophysics Data System (ADS)

Markovich, Tomer; Andelman, David; Podgornik, Rudi

2017-10-01

We generalize the concept of charge regulation of ionic solutions, and apply it to complex fluids with mobile macro-ions having internal non-electrostatic degrees of freedom. The suggested framework provides a convenient tool for investigating systems where mobile macro-ions can self-regulate their charge (e.g., proteins). We show that even within a simplified charge-regulation model, the charge dissociation equilibrium results in different and notable properties. Consequences of the charge regulation include a positional dependence of the effective charge of the macro-ions, a non-monotonic dependence of the effective Debye screening length on the concentration of the monovalent salt, a modification of the electric double-layer structure, and buffering by the macro-ions of the background electrolyte.

Manufacturing a thin wire electrostatic trap for ultracold polar molecules.

PubMed

Kleinert, J; Haimberger, C; Zabawa, P J; Bigelow, N P

2007-11-01

We present a detailed description on how to build a thin wire electrostatic trap (TWIST) for ultracold polar molecules. It is the first design of an electrostatic trap that can be superimposed directly onto a magneto-optical trap (MOT). We can thus continuously produce ultracold polar molecules via photoassociation from a two species MOT and instantaneously trap them in the TWIST without the need for complex transfer schemes. Despite the spatial overlap of the TWIST and the MOT, the two traps can be operated and optimized completely independently due to the complementary nature of the utilized trapping mechanisms.

Electrostatic formation of liquid marbles and agglomerates

NASA Astrophysics Data System (ADS)

Liyanaarachchi, K. R.; Ireland, P. M.; Webber, G. B.; Galvin, K. P.

2013-07-01

We report observations of a sudden, explosive release of electrostatically charged 100 μm glass beads from a particle bed. These cross an air gap of several millimeters, are engulfed by an approaching pendant water drop, and form a metastable spherical agglomerate on the bed surface. The stability transition of the particle bed is explained by promotion of internal friction by in-plane electrostatic stresses. The novel agglomerates formed this way resemble the "liquid marbles" formed by coating a drop with hydrophobic particles. Complex multi-layered agglomerates may also be produced by this method, with potential industrial, pharmaceutical, environmental, and biological applications.

Coarse Grained Model for Biological Simulations: Recent Refinements and Validation

PubMed Central

Vicatos, Spyridon; Rychkova, Anna; Mukherjee, Shayantani; Warshel, Arieh

2014-01-01

Exploring the free energy landscape of proteins and modeling the corresponding functional aspects presents a major challenge for computer simulation approaches. This challenge is due to the complexity of the landscape and the enormous computer time needed for converging simulations. The use of various simplified coarse grained (CG) models offers an effective way of sampling the landscape, but most current models are not expected to give a reliable description of protein stability and functional aspects. The main problem is associated with insufficient focus on the electrostatic features of the model. In this respect our recent CG model offers significant advantage as it has been refined while focusing on its electrostatic free energy. Here we review the current state of our model, describing recent refinement, extensions and validation studies while focusing on demonstrating key applications. These include studies of protein stability, extending the model to include membranes and electrolytes and electrodes as well as studies of voltage activated proteins, protein insertion trough the translocon, the action of molecular motors and even the coupling of the stalled ribosome and the translocon. Our example illustrates the general potential of our approach in overcoming major challenges in studies of structure function correlation in proteins and large macromolecular complexes. PMID:25050439

Numerical Methods of Computational Electromagnetics for Complex Inhomogeneous Systems

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

Cai, Wei

Understanding electromagnetic phenomena is the key in many scientific investigation and engineering designs such as solar cell designs, studying biological ion channels for diseases, and creating clean fusion energies, among other things. The objectives of the project are to develop high order numerical methods to simulate evanescent electromagnetic waves occurring in plasmon solar cells and biological ion-channels, where local field enhancement within random media in the former and long range electrostatic interactions in the latter are of major challenges for accurate and efficient numerical computations. We have accomplished these objectives by developing high order numerical methods for solving Maxwell equationsmore » such as high order finite element basis for discontinuous Galerkin methods, well-conditioned Nedelec edge element method, divergence free finite element basis for MHD, and fast integral equation methods for layered media. These methods can be used to model the complex local field enhancement in plasmon solar cells. On the other hand, to treat long range electrostatic interaction in ion channels, we have developed image charge based method for a hybrid model in combining atomistic electrostatics and continuum Poisson-Boltzmann electrostatics. Such a hybrid model will speed up the molecular dynamics simulation of transport in biological ion-channels.« less

Crystal structure of a soluble form of human monoglyceride lipase in complex with an inhibitor at 1.35 Å resolution

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

Schalk-Hihi, Céline; Schubert, Carsten; Alexander, Richard

2011-12-22

A high-resolution structure of a ligand-bound, soluble form of human monoglyceride lipase (MGL) is presented. The structure highlights a novel conformation of the regulatory lid-domain present in the lipase family as well as the binding mode of a pharmaceutically relevant reversible inhibitor. Analysis of the structure lacking the inhibitor indicates that the closed conformation can accommodate the native substrate 2-arachidonoyl glycerol. A model is proposed in which MGL undergoes conformational and electrostatic changes during the catalytic cycle ultimately resulting in its dissociation from the membrane upon completion of the cycle. In addition, the study outlines a successful approach to transformmore » membrane associated proteins, which tend to aggregate upon purification, into a monomeric and soluble form.« less

[Molecular dynamics of immune complex of photoadduct-containing DNA with Fab-Anti-DNA antibody fragment].

PubMed

Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

2016-01-01

Antibodies to DNA play an important role in the pathogenesis of autoimmune diseases. The elucidation of structural mechanisms of both the antigen recognition and the interaction of anti-DNA antibodies with DNA will help to understand the role of DNA-containing immune complexes in various pathologies and can provide a basis for new treatment modalities. Moreover, the DNA-antibody complex is an analog of specific intracellular DNA-protein interactions. In this work, we used in silico molecular dynamic simulations of bimolecular complexes of the dsDNA segment containing the Fab fragment of an anti-DNA antibody to obtain the detailed thermodynamic and structural characteristics of dynamic intermolecular interactions. Using computationally modified crystal structure of the Fab-DNA complex (PDB ID: 3VW3), we studied the equilibrium molecular dynamics of the 64M-5 antibody Fab fragment associated with the dsDNA fragment containing the thymine dimer, the product of DNA photodamage. Amino acid residues that constitute paratopes and the complementary nucleotide epitopes for the Fab-DNA construct were identified. Stacking and electrostatic interactions were found to play the main role in mediating the most specific antibody-dsDNA contacts, while hydrogen bonds were less significant. These findings may shed light on the formation and properties of pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus associated with skin photosensitivity and DNA photodamage.

A theoretical study of complexes formed between cations and curved aromatic systems: electrostatics does not always control cation-π interaction.

PubMed

Carrazana-García, Jorge A; Cabaleiro-Lago, Enrique M; Rodríguez-Otero, Jesús

2017-04-19

The present work studies the interaction of two extended curved π-systems (corannulene and sumanene) with various cations (sodium, potassium, ammonium, tetramethylammonium, guanidinium and imidazolium). Polyatomic cations are models of groups found in important biomolecules in which cation-π interaction plays a fundamental role. The results indicate an important size effect: with extended π systems and cations of the size of potassium and larger, dispersion is much more important than has been generally recognized for cation-π interactions. In most of the systems studied here, the stability of the cation-π complexes is the result of a balanced combination of electrostatic, induction and dispersion contributions. None of the systems studied here owes its stability to the electrostatic interaction more than 42%. Induction dominates stabilization in complexes with sodium, and in some of the potassium and ammonium complexes. In complexes with large cations and with flat cations dispersion is the major stabilizing contribution and can provide more than 50% of the stabilization energy. This implies that theoretical studies of the cation-π interaction involving large or even medium-size fragments require a level of calculation capable of properly modelling dispersion. The separation between the cation and the π system is another important factor to take into account, especially when the fragments of the cation-π complex are bound (for example, to a protein backbone) and cannot interact at the most favourable distance.

Contribution of Electrostatics to the Kinetics of Electron Transfer from NADH-Cytochrome b5 Reductase to Fe(III)-Cytochrome b5.

PubMed

Kollipara, Sireesha; Tatireddy, Shivakishore; Pathirathne, Thusitha; Rathnayake, Lasantha K; Northrup, Scott H

2016-08-25

Brownian dynamics (BD) simulations provide here a theoretical atomic-level treatment of the reduction of human ferric cytochrome b5 (cyt b5) by NADH-cytochrome b5 reductaste (cyt b5r) and several of its mutants. BD is used to calculate the second-order rate constant of electron transfer (ET) between the proteins for direct correlation with experiments. Interestingly, the inclusion of electrostatic forces dramatically increases the reaction rate of the native proteins despite the overall negative charge of both proteins. The role played by electrostatic charge distribution in stabilizing the ET complexes and the role of mutations of several amino acid residues in stabilizing or destabilizing the complexes are analyzed. The complex with the shortest ET reaction distance (d = 6.58 Å) from rigid body BD is further subjected to 1 ns of molecular dynamics (MD) in a periodic box of TIP3P water to produce a more stable complex allowed by flexibility and with a shorter average reaction distance d = 6.02 Å. We predict a docking model in which the following ion-ion interactions are dominant (cyt b5r/cyt b5): Lys162-Heme O1D/Lys163-Asp64/Arg91-Heme O1A/Lys125-Asp70.

Accurate prediction of polarised high order electrostatic interactions for hydrogen bonded complexes using the machine learning method kriging.

PubMed

Hughes, Timothy J; Kandathil, Shaun M; Popelier, Paul L A

2015-02-05

As intermolecular interactions such as the hydrogen bond are electrostatic in origin, rigorous treatment of this term within force field methodologies should be mandatory. We present a method able of accurately reproducing such interactions for seven van der Waals complexes. It uses atomic multipole moments up to hexadecupole moment mapped to the positions of the nuclear coordinates by the machine learning method kriging. Models were built at three levels of theory: HF/6-31G(**), B3LYP/aug-cc-pVDZ and M06-2X/aug-cc-pVDZ. The quality of the kriging models was measured by their ability to predict the electrostatic interaction energy between atoms in external test examples for which the true energies are known. At all levels of theory, >90% of test cases for small van der Waals complexes were predicted within 1 kJ mol(-1), decreasing to 60-70% of test cases for larger base pair complexes. Models built on moments obtained at B3LYP and M06-2X level generally outperformed those at HF level. For all systems the individual interactions were predicted with a mean unsigned error of less than 1 kJ mol(-1). Copyright © 2013 Elsevier B.V. All rights reserved.

A complex study of 5-amino-3-methyl-4-[2-(5-amino-1,3,4-oxadiazolo)]-isoxazole monohydrate: A new low-molecular-weight immune response modifier

NASA Astrophysics Data System (ADS)

Ryng, Stanisław; Zimecki, Michał; Jezierska-Mazzarello, Aneta; Panek, Jarosław J.; Mączyński, Marcin; Głowiak, Tadeusz; Sawka-Dobrowolska, Wanda; Koll, Aleksander

2011-07-01

A new potential lead structure with immunological activity, 5-amino-3-methyl-4-[2-(5-amino-1,3,4-oxadiazolo)]-isoxazole monohydrate, was synthesized. A detailed description of synthesis is presented together with X-ray structural analysis. In vitro assays showed that the compound had a potent immunosuppressive activity. Next, Density Functional Theory (DFT) was employed to shed a light on molecular properties of the investigated isoxazole derivative. The molecular modeling part included geometric as well as electronic structure descriptions: (i) the conformational analysis was performed to localize the most appropriate conformation; (ii) the coordination energy and Basis Set Superposition Error (BSSE) were estimated for the complex of the isoxazole derivative interacting with water molecule; (iii) the potential energy distribution was used to assign molecular vibrations, and NBO population analysis served to describe the electronic structure; (iv) the electrostatic potential map was generated to provide the graphical presentation of regions exposed for intermolecular interactions. The contacts between the water molecule and the nitrogen atom of the isoxazole ring edge were present in the solid phase. On the other hand, the theoretical DFT prediction was that the oxygen atom of the edge should form a more stable complex with the water molecule.

Grid-Based Projector Augmented Wave (GPAW) Implementation of Quantum Mechanics/Molecular Mechanics (QM/MM) Electrostatic Embedding and Application to a Solvated Diplatinum Complex.

PubMed

Dohn, A O; Jónsson, E Ö; Levi, G; Mortensen, J J; Lopez-Acevedo, O; Thygesen, K S; Jacobsen, K W; Ulstrup, J; Henriksen, N E; Møller, K B; Jónsson, H

2017-12-12

A multiscale density functional theory-quantum mechanics/molecular mechanics (DFT-QM/MM) scheme is presented, based on an efficient electrostatic coupling between the electronic density obtained from a grid-based projector augmented wave (GPAW) implementation of density functional theory and a classical potential energy function. The scheme is implemented in a general fashion and can be used with various choices for the descriptions of the QM or MM regions. Tests on H 2 O clusters, ranging from dimer to decamer show that no systematic energy errors are introduced by the coupling that exceeds the differences in the QM and MM descriptions. Over 1 ns of liquid water, Born-Oppenheimer QM/MM molecular dynamics (MD) are sampled combining 10 parallel simulations, showing consistent liquid water structure over the QM/MM border. The method is applied in extensive parallel MD simulations of an aqueous solution of the diplatinum [Pt 2 (P 2 O 5 H 2 ) 4 ] 4- complex (PtPOP), spanning a total time period of roughly half a nanosecond. An average Pt-Pt distance deviating only 0.01 Å from experimental results, and a ground-state Pt-Pt oscillation frequency deviating by <2% from experimental results were obtained. The simulations highlight a remarkable harmonicity of the Pt-Pt oscillation, while also showing clear signs of Pt-H hydrogen bonding and directional coordination of water molecules along the Pt-Pt axis of the complex.

Al-Coated Conductive Fiber Filters for High-Efficiency Electrostatic Filtration: Effects of Electrical and Fiber Structural Properties.

PubMed

Choi, Dong Yun; An, Eun Jeong; Jung, Soo-Ho; Song, Dong Keun; Oh, Yong Suk; Lee, Hyung Woo; Lee, Hye Moon

2018-04-10

Through the direct decomposition of an Al precursor ink AlH 3 {O(C 4 H 9 ) 2 }, we fabricated an Al-coated conductive fiber filter for the efficient electrostatic removal of airborne particles (>99%) with a low pressure drop (~several Pascals). The effects of the electrical and structural properties of the filters were investigated in terms of collection efficiency, pressure drop, and particle deposition behavior. The collection efficiency did not show a significant correlation with the extent of electrical conductivity, as the filter is electrostatically charged by the metallic Al layers forming electrical networks throughout the fibers. Most of the charged particles were collected via surface filtration by Coulombic interactions; consequently, the filter thickness had little effect on the collection efficiency. Based on simulations of various fiber structures, we found that surface filtration can transition to depth filtration depending on the extent of interfiber distance. Therefore, the effects of structural characteristics on collection efficiency varied depending on the degree of the fiber packing density. This study will offer valuable information pertaining to the development of a conductive metal/polymer composite air filter for an energy-efficient and high-performance electrostatic filtration system.

Krebs cycle metabolon: structural evidence of substrate channeling revealed by cross-linking and mass spectrometry.

PubMed

Wu, Fei; Minteer, Shelley

2015-02-02

It has been hypothesized that the high metabolic flux in the mitochondria is due to the self-assembly of enzyme supercomplexes (called metabolons) that channel substrates from one enzyme to another, but there has been no experimental confirmation of this structure or the channeling. A structural investigation of enzyme organization within the Krebs cycle metabolon was accomplished by in vivo cross-linking and mass spectrometry. Eight Krebs cycle enzyme components were isolated upon chemical fixation, and interfacial residues between mitochondrial malate dehydrogenase, citrate synthase, and aconitase were identified. Using constraint protein docking, a low-resolution structure for the three-enzyme complex was achieved, as well as the two-fold symmetric octamer. Surface analysis showed formation of electrostatic channeling upon protein-protein association, which is the first structural evidence of substrate channeling in the Krebs cycle metabolon. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Understanding the physical basis of the salt dependence of the electrostatic binding free energy of mutated charged ligand-nucleic acid complexes.

PubMed

Harris, Robert C; Bredenberg, Johan H; Silalahi, Alexander R J; Boschitsch, Alexander H; Fenley, Marcia O

2011-06-01

The predictions of the derivative of the electrostatic binding free energy of a biomolecular complex, ΔG(el), with respect to the logarithm of the 1:1 salt concentration, d(ΔG(el))/d(ln[NaCl]), SK, by the Poisson-Boltzmann equation, PBE, are very similar to those of the simpler Debye-Hückel equation, DHE, because the terms in the PBE's predictions of SK that depend on the details of the dielectric interface are small compared to the contributions from long-range electrostatic interactions. These facts allow one to obtain predictions of SK using a simplified charge model along with the DHE that are highly correlated with both the PBE and experimental binding data. The DHE-based model developed here, which was derived from the generalized Born model, explains the lack of correlation between SK and ΔG(el) in the presence of a dielectric discontinuity, which conflicts with the popular use of this supposed correlation to parse experimental binding free energies into electrostatic and nonelectrostatic components. Moreover, the DHE model also provides a clear justification for the correlations between SK and various empirical quantities, like the number of ion pairs, the ligand charge on the interface, the Coulomb binding free energy, and the product of the charges on the complex's components, but these correlations are weak, questioning their usefulness. Copyright © 2011 Elsevier B.V. All rights reserved.

Electrostatically Accelerated Coupled Binding and Folding of Intrinsically Disordered Proteins

PubMed Central

Ganguly, Debabani; Otieno, Steve; Waddell, Brett; Iconaru, Luigi; Kriwacki, Richard W.; Chen, Jianhan

2012-01-01

Intrinsically disordered proteins (IDPs) are now recognized to be prevalent in biology, and many potential functional benefits have been discussed. However, the frequent requirement of peptide folding in specific interactions of IDPs could impose a kinetic bottleneck, which could be overcome only by efficient folding upon encounter. Intriguingly, existing kinetic data suggest that specific binding of IDPs is generally no slower than that of globular proteins. Here, we exploited the cell cycle regulator p27Kip1 (p27) as a model system to understand how IDPs might achieve efficient folding upon encounter for facile recognition. Combining experiments and coarse-grained modeling, we demonstrate that long-range electrostatic interactions between enriched charges on p27 and near its binding site on cyclin A not only enhance the encounter rate (i.e., electrostatic steering), but also promote folding-competent topologies in the encounter complexes, allowing rapid subsequent formation of short-range native interactions en route to the specific complex. In contrast, nonspecific hydrophobic interactions, while hardly affecting the encounter rate, can significantly reduce the efficiency of folding upon encounter and lead to slower binding kinetics. Further analysis of charge distributions in a set of known IDP complexes reveals that, although IDP binding sites tend to be more hydrophobic compared to the rest of the target surface, their vicinities are frequently enriched with charges to complement those on IDPs. This observation suggests that electrostatically accelerated encounter and induced folding might represent a prevalent mechanism for promoting facile IDP recognition. PMID:22721951

A Thermodynamic Model for Genome Packaging in Hepatitis B Virus.

PubMed

Kim, Jehoon; Wu, Jianzhong

2015-10-20

Understanding the fundamentals of genome packaging in viral capsids is important for finding effective antiviral strategies and for utilizing benign viral particles for gene therapy. While the structure of encapsidated genomic materials has been routinely characterized with experimental techniques such as cryo-electron microscopy and x-ray diffraction, much less is known about the molecular driving forces underlying genome assembly in an intracellular environment and its in vivo interactions with the capsid proteins. Here we study the thermodynamic basis of the pregenomic RNA encapsidation in human Hepatitis B virus in vivo using a coarse-grained molecular model that captures the essential components of nonspecific intermolecular interactions. The thermodynamic model is used to examine how the electrostatic interaction between the packaged RNA and the highly charged C-terminal domains (CTD) of capsid proteins regulate the nucleocapsid formation. The theoretical model predicts optimal RNA content in Hepatitis B virus nucleocapsids with different CTD lengths in good agreement with mutagenesis measurements, confirming the predominant role of electrostatic interactions and molecular excluded-volume effects in genome packaging. We find that the amount of encapsidated RNA is not linearly correlated with the net charge of CTD tails as suggested by earlier theoretical studies. Our thermodynamic analysis of the nucleocapsid structure and stability indicates that ∼10% of the CTD residues are free from complexation with RNA, resulting in partially exposed CTD tails. The thermodynamic model also predicts the free energy of complex formation between macromolecules, which corroborates experimental results for the impact of CTD truncation on the nucleocapsid stability. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Mg2+ in the Major Groove Modulates B-DNA Structure and Dynamics

PubMed Central

Guéroult, Marc; Boittin, Olivier; Mauffret, Oliver; Etchebest, Catherine; Hartmann, Brigitte

2012-01-01

This study investigates the effect of Mg2+ bound to the DNA major groove on DNA structure and dynamics. The analysis of a comprehensive dataset of B-DNA crystallographic structures shows that divalent cations are preferentially located in the DNA major groove where they interact with successive bases of (A/G)pG and the phosphate group of 5′-CpA or TpG. Based on this knowledge, molecular dynamics simulations were carried out on a DNA oligomer without or with Mg2+ close to an ApG step. These simulations showed that the hydrated Mg2+ forms a stable intra-strand cross-link between the two purines in solution. ApG generates an electrostatic potential in the major groove that is particularly attractive for cations; its intrinsic conformation is well-adapted to the formation of water-mediated hydrogen bonds with Mg2+. The binding of Mg2+ modulates the behavior of the 5′-neighboring step by increasing the BII (ε-ζ>0°) population of its phosphate group. Additional electrostatic interactions between the 5′-phosphate group and Mg2+ strengthen both the DNA-cation binding and the BII character of the 5′-step. Cation binding in the major groove may therefore locally influence the DNA conformational landscape, suggesting a possible avenue for better understanding how strong DNA distortions can be stabilized in protein-DNA complexes. PMID:22844516

Adsorption and release of ofloxacin from acid- and heat-treated halloysite.

PubMed

Wang, Qin; Zhang, Junping; Zheng, Yue; Wang, Aiqin

2014-01-01

Halloysite nanotube is an ideal vehicle of the controlled release of drugs. In this study, we systematically investigated the effects of acid- and heat-treatments on the physicochemical properties, structure and morphology of halloysite by XRD, FTIR, SEM and TEM. Afterwards, the adsorption and in vitro release properties of halloysite for cationic ofloxacin (OFL) were evaluated. The results indicate that HCl treatment has no influence on the crystal structure of halloysite, whereas it becomes amorphous after calcined at temperature higher than 500 °C. Both acid- and heat-treatments have no evident influence on the tubular structure of halloysite. OFL was adsorbed onto halloysite via electrostatic interaction between protonated OFL and negative halloysite surface, cation exchange as well as electrostatic interaction between the OFL-Al(3+) complexes and the negative halloysite surface. Acid-treatment facilitates the release of the adsorbed OFL compared with the natural halloysite in spite of a slight decrease of adsorption capacity. However, heat-treatment results in a sharp decrease of adsorption capacity for OFL owning to the OFL-promoted dissolution of aluminum and the disappearance of the porous structure. Although heat-treatment also facilitates release of the adsorbed OFL, the amount of OFL released is in fact less than the natural halloysite owing to the very low adsorption capacity. Thus, acid-activation is an effective protocol to improve the adsorption and release of halloysite for cationic drug molecules. Copyright © 2013 Elsevier B.V. All rights reserved.

DOCLASP - Docking ligands to target proteins using spatial and electrostatic congruence extracted from a known holoenzyme and applying simple geometrical transformations.

PubMed

Chakraborty, Sandeep

2014-01-01

The ability to accurately and effectively predict the interaction between proteins and small drug-like compounds has long intrigued researchers for pedagogic, humanitarian and economic reasons. Protein docking methods (AutoDock, GOLD, DOCK, FlexX and Glide to name a few) rank a large number of possible conformations of protein-ligand complexes using fast algorithms. Previously, it has been shown that structural congruence leading to the same enzymatic function necessitates the congruence of electrostatic properties (CLASP). The current work presents a methodology for docking a ligand into a target protein, provided that there is at least one known holoenzyme with ligand bound - DOCLASP (Docking using CLASP). The contact points of the ligand in the holoenzyme defines a motif, which is used to query the target enzyme using CLASP. If there are significant matches, the holoenzyme and the target protein are superimposed based on congruent atoms. The same linear and rotational transformations are also applied to the ligand, thus creating a unified coordinate framework having the holoenzyme, the ligand and the target enzyme. In the current work, the dipeptidyl peptidase-IV inhibitor vildagliptin was docked to the PI-PLC structure complexed with myo-inositol using DOCLASP. Also, corroboration of the docking of phenylthiourea to the modelled structure of polyphenol oxidase (JrPPO1) from walnut is provided based on the subsequently solved structure of JrPPO1 (PDBid:5CE9). Analysis of the binding of the antitrypanosomial drug suramin to nine non-homologous proteins in the PDB database shows a diverse set of binding motifs, and multiple binding sites in the phospholipase A2-likeproteins from the Bothrops genus of pitvipers. The conformational changes in the suramin molecule on binding highlights the challenges in docking flexible ligands into an already 'plastic' binding site. Thus, DOCLASP presents a method for 'soft docking' ligands to proteins with low computational requirements.

Cationic polymers for DNA origami coating - examining their binding efficiency and tuning the enzymatic reaction rates

NASA Astrophysics Data System (ADS)

Kiviaho, Jenny K.; Linko, Veikko; Ora, Ari; Tiainen, Tony; Järvihaavisto, Erika; Mikkilä, Joona; Tenhu, Heikki; Nonappa, Affc; Kostiainen, Mauri A.

2016-06-01

DNA origamis are fully tailored, programmable, biocompatible and readily functionalizable nanostructures that provide an excellent foundation for the development of sophisticated drug-delivery systems. However, the DNA origami objects suffer from certain drawbacks such as low cell-transfection rates and low stability. A great deal of studies on polymer-based transfection agents, mainly focusing on polyplex formation and toxicity, exists. In this study, the electrostatic binding between a brick-like DNA origami and cationic block-copolymers was explored. The effect of the polymer structure on the binding was investigated and the toxicity of the polymer-origami complexes evaluated. The study shows that all of the analyzed polymers had a suitable binding efficiency irrespective of the block structure. It was also observed that the toxicity of polymer-origami complexes was insignificant at the biologically relevant concentration levels. Besides brick-like DNA origamis, tubular origami carriers equipped with enzymes were also coated with the polymers. By adjusting the amount of cationic polymers that cover the DNA structures, we showed that it is possible to control the enzyme kinetics of the complexes. This work gives a starting point for further development of biocompatible and effective polycation-based block copolymers that can be used in coating different DNA origami nanostructures for various bioapplications.DNA origamis are fully tailored, programmable, biocompatible and readily functionalizable nanostructures that provide an excellent foundation for the development of sophisticated drug-delivery systems. However, the DNA origami objects suffer from certain drawbacks such as low cell-transfection rates and low stability. A great deal of studies on polymer-based transfection agents, mainly focusing on polyplex formation and toxicity, exists. In this study, the electrostatic binding between a brick-like DNA origami and cationic block-copolymers was explored. The effect of the polymer structure on the binding was investigated and the toxicity of the polymer-origami complexes evaluated. The study shows that all of the analyzed polymers had a suitable binding efficiency irrespective of the block structure. It was also observed that the toxicity of polymer-origami complexes was insignificant at the biologically relevant concentration levels. Besides brick-like DNA origamis, tubular origami carriers equipped with enzymes were also coated with the polymers. By adjusting the amount of cationic polymers that cover the DNA structures, we showed that it is possible to control the enzyme kinetics of the complexes. This work gives a starting point for further development of biocompatible and effective polycation-based block copolymers that can be used in coating different DNA origami nanostructures for various bioapplications. Electronic supplementary information (ESI) available: Details of materials, syntheses of the polymers, fabrication and purification of DNA origamis, luminescence decay assays, agarose gel electrophoresis, ethidium bromide displacement assay, MTT assay and TEM characterization. See DOI: 10.1039/c5nr08355a

Redox Specificity of 2-Hydroxyacid-Coupled NAD+/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics

PubMed Central

Durani, Susheel

2013-01-01

With “reactive” arginine as a kinetic reporter, 2-hydroxyacid dehydrogenases are assessed in basis of their specialization as NAD+-reducing or NADH-oxidizing enzymes. Specifically, M4 and H4 lactate dehydrogenases (LDHs) and cytoplasmic and mitochondrial malate dehydrogenases (MDHs) are compared to assess if their coenzyme specificity may involve electrostatics of cationic or neutral nicotinamide structure as the basis. The enzymes from diverse eukaryote and prokaryote sources thus are assessed in “reactivity” of functionally-critical arginine as a function of salt concentration and pH. Electrostatic calculations were performed on “reactive” arginines and found good correspondence with experiment. The reductive and oxidative LDHs and MDHs are assessed in their count over ionizable residues and in placement details of the residues in their structures as proteins. The variants found to be high or low in ΔpKa of “reactive” arginine are found to be also strong or weak cations that preferentially oxidize NADH (neutral nicotinamide structure) or reduce NAD+ (cationic nicotinamide structure). The ionized groups of protein structure may thus be important to redox specificity of the enzyme on basis of electrostatic preference for the oxidized (cationic nicotinamide) or reduced (neutral nicotinamide) coenzyme. Detailed comparisons of isozymes establish that the residues contributing in their redox specificity are scrambled in structure of the reductive enzyme. PMID:24391777

Cation–π interactions in protein–ligand binding: theory and data-mining reveal different roles for lysine and arginine† †Electronic supplementary information (ESI) available: DLPNO-CCSD(T)/aug-cc-pVnZ benchmarks; PLIP geometric criteria; polycyclic aromatic ring visualizations; van der Waals surfaces of model complexes; absolute energies from DLPNO-CCSD(T)/aug-cc-pVTZ and SAPT2+3/aug-cc-pVDZ calculations; Cartesian coordinates; Table of PDB IDs and corresponding cation–π interactions identified (.xls). See DOI: 10.1039/c7sc04905f

PubMed Central

Kumar, Kiran; Woo, Shin M.; Siu, Thomas; Cortopassi, Wilian A.

2018-01-01

We have studied the cation–π interactions of neutral aromatic ligands with the cationic amino acid residues arginine, histidine and lysine using ab initio calculations, symmetry adapted perturbation theory (SAPT), and a systematic meta-analysis of all available Protein Data Bank (PDB) X-ray structures. Quantum chemical potential energy surfaces (PES) for these interactions were obtained at the DLPNO-CCSD(T) level of theory and compared against the empirical distribution of 2012 unique protein–ligand cation–π interactions found in X-ray crystal structures. We created a workflow to extract these structures from the PDB, filtering by interaction type and residue pKa. The gas phase cation–π interaction of lysine is the strongest by more than 10 kcal mol–1, but the empirical distribution of 582 X-ray structures lies away from the minimum on the interaction PES. In contrast, 1381 structures involving arginine match the underlying calculated PES with good agreement. SAPT analysis revealed that underlying differences in the balance of electrostatic and dispersion contributions are responsible for this behavior in the context of the protein environment. The lysine–arene interaction, dominated by electrostatics, is greatly weakened by a surrounding dielectric medium and causes it to become essentially negligible in strength and without a well-defined equilibrium separation. The arginine–arene interaction involves a near equal mix of dispersion and electrostatic attraction, which is weakened to a much smaller degree by the surrounding medium. Our results account for the paucity of cation–π interactions involving lysine, even though this is a more common residue than arginine. Aromatic ligands are most likely to interact with cationic arginine residues as this interaction is stronger than for lysine in higher polarity surroundings. PMID:29719674

Trapping of muscle relaxant methocarbamol degradation product by complexation with copper(II) ion: Spectroscopic and quantum chemical studies

NASA Astrophysics Data System (ADS)

Mansour, Ahmed M.; Shehab, Ola R.

2014-07-01

Structural properties of methocarbamol (Mcm) were extensively studied both experimentally and theoretically using FT IR, 1H NMR, UV-Vis., geometry optimization, Mulliken charge, and molecular electrostatic potential. Stability arises from hyper-conjugative interactions, charge delocalization and H-bonding was analyzed using natural bond orbital (NBO) analysis. Mcm was decomposed in ethanol/water mixture at 80 °C to guaifenesin [(RS)-3-(2-methoxyphenoxy)propane-1,2-diol] and carbamate ion [NH2COO-], where the degradation mechanism was explained by trapping the carbamate ion via the complexation with copper(II) ion. The structure of the isolated complex ([Cu(NH2COO)2(H2O)]ṡ4H2O) was elucidated by spectral, thermal, and magnetic tools. Electronic spectra were discussed by TD-DFT and the descriptions of frontier molecular orbitals and the relocations of the electron density were determined. Calculated g-tensor values showed best agreement with experimental values from EPR when carried out using both the B3LYP and B3PW91 functional.

Lanthanide and transition metal complexes of bioactive coumarins: molecular modeling and spectroscopic studies.

PubMed

Georgieva, I; Mihaylov, Tz; Trendafilova, N

2014-06-01

The present paper summarizes theoretical and spectroscopic investigations on a series of active coumarins and their lanthanide and transition metal complexes with application in medicine and pharmacy. Molecular modeling as well as IR, Raman, NMR and electronic spectral simulations at different levels of theory were performed to obtain important molecular descriptors: total energy, formation energy, binding energy, stability, conformations, structural parameters, electron density distribution, molecular electrostatic potential, Fukui functions, atomic charges, and reactive indexes. The computations are performed both in gas phase and in solution with consideration of the solvent effect on the molecular structural and energetic parameters. The investigations have shown that the advanced computational methods are reliable for prediction of the metal-coumarin binding mode, electron density distribution, thermodynamic properties as well as the strength and nature of the metal-coumarin interaction (not experimentally accessible) and correctly interpret the experimental spectroscopic data. Known results from biological tests for cytotoxic, antimicrobial, anti-fungal, spasmolytic and anti-HIV activities on the studied metal complexes are reported and discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

Energetic and flexibility properties captured by long molecular dynamics simulations of a membrane-embedded pMHCII-TCR complex.

PubMed

Bello, Martiniano; Correa-Basurto, José

2016-04-01

Although crystallographic data have provided important molecular insight into the interactions in the pMHC-TCR complex, the inherent features of this structural approach cause it to only provide a static picture of the interactions. While unbiased molecular dynamics simulations (UMDSs) have provided important information about the dynamic structural behavior of the pMHC-TCR complex, most of them have modeled the pMHC-TCR complex as soluble, when in physiological conditions, this complex is membrane bound; therefore, following this latter UMDS protocol might hamper important dynamic results. In this contribution, we performed three independent 300 ns-long UMDSs of the pMHCII-TCR complex anchored in two opposing membranes to explore the structural and energetic properties of the recognition of pMHCII by the TCR. The conformational ensemble generated through UMDSs was subjected to clustering and Cartesian principal component analyses (cPCA) to explore the dynamical behavior of the pMHCII-TCR association. Furthermore, based on the conformational population sampled through UMDSs, the effective binding free energy, per-residue free energy decomposition, and alanine scanning mutations were explored for the native pMHCII-TCR complex, as well as for 12 mutations (p1-p12MHCII-TCR) introduced in the native peptide. Clustering analyses and cPCA provide insight into the rocking motion of the TCR onto pMHCII, together with the presence of new electrostatic interactions not observed through crystallographic methods. Energetic results provide evidence of the main contributors to the pMHC-TCR complex formation as well as the key residues involved in this molecular recognition process.

Electric potential and electric field imaging

NASA Astrophysics Data System (ADS)

Generazio, E. R.

2017-02-01

The technology and methods for remote quantitative imaging of electrostatic potentials and electrostatic fields in and around objects and in free space is presented. Electric field imaging (EFI) technology may be applied to characterize intrinsic or existing electric potentials and electric fields, or an externally generated electrostatic field made be used for "illuminating" volumes to be inspected with EFI. The baseline sensor technology (e-Sensor) and its construction, optional electric field generation (quasi-static generator), and current e-Sensor enhancements (ephemeral e-Sensor) are discussed. Demonstrations for structural, electronic, human, and memory applications are shown. This new EFI capability is demonstrated to reveal characterization of electric charge distribution creating a new field of study embracing areas of interest including electrostatic discharge (ESD) mitigation, crime scene forensics, design and materials selection for advanced sensors, dielectric morphology of structures, tether integrity, organic molecular memory, and medical diagnostic and treatment efficacy applications such as cardiac polarization wave propagation and electromyography imaging.

Electrostatic Effects in Filamentous Protein Aggregation

PubMed Central

Buell, Alexander K.; Hung, Peter; Salvatella, Xavier; Welland, Mark E.; Dobson, Christopher M.; Knowles, Tuomas P.J.

2013-01-01

Electrostatic forces play a key role in mediating interactions between proteins. However, gaining quantitative insights into the complex effects of electrostatics on protein behavior has proved challenging, due to the wide palette of scenarios through which both cations and anions can interact with polypeptide molecules in a specific manner or can result in screening in solution. In this article, we have used a variety of biophysical methods to probe the steady-state kinetics of fibrillar protein self-assembly in a highly quantitative manner to detect how it is modulated by changes in solution ionic strength. Due to the exponential modulation of the reaction rate by electrostatic forces, this reaction represents an exquisitely sensitive probe of these effects in protein-protein interactions. Our approach, which involves a combination of experimental kinetic measurements and theoretical analysis, reveals a hierarchy of electrostatic effects that control protein aggregation. Furthermore, our results provide a highly sensitive method for the estimation of the magnitude of binding of a variety of ions to protein molecules. PMID:23473495

DEPPDB - DNA electrostatic potential properties database. Electrostatic properties of genome DNA elements.

PubMed

Osypov, Alexander A; Krutinin, Gleb G; Krutinina, Eugenia A; Kamzolova, Svetlana G

2012-04-01

Electrostatic properties of genome DNA are important to its interactions with different proteins, in particular, related to transcription. DEPPDB - DNA Electrostatic Potential (and other Physical) Properties Database - provides information on the electrostatic and other physical properties of genome DNA combined with its sequence and annotation of biological and structural properties of genomes and their elements. Genomes are organized on taxonomical basis, supporting comparative and evolutionary studies. Currently, DEPPDB contains all completely sequenced bacterial, viral, mitochondrial, and plastids genomes according to the NCBI RefSeq, and some model eukaryotic genomes. Data for promoters, regulation sites, binding proteins, etc., are incorporated from established DBs and literature. The database is complemented by analytical tools. User sequences calculations are available. Case studies discovered electrostatics complementing DNA bending in E.coli plasmid BNT2 promoter functioning, possibly affecting host-environment metabolic switch. Transcription factors binding sites gravitate to high potential regions, confirming the electrostatics universal importance in protein-DNA interactions beyond the classical promoter-RNA polymerase recognition and regulation. Other genome elements, such as terminators, also show electrostatic peculiarities. Most intriguing are gene starts, exhibiting taxonomic correlations. The necessity of the genome electrostatic properties studies is discussed.

Deppdb--DNA electrostatic potential properties database: electrostatic properties of genome DNA.

PubMed

Osypov, Alexander A; Krutinin, Gleb G; Kamzolova, Svetlana G

2010-06-01

The electrostatic properties of genome DNA influence its interactions with different proteins, in particular, the regulation of transcription by RNA-polymerases. DEPPDB--DNA Electrostatic Potential Properties Database--was developed to hold and provide all available information on the electrostatic properties of genome DNA combined with its sequence and annotation of biological and structural properties of genome elements and whole genomes. Genomes in DEPPDB are organized on a taxonomical basis. Currently, the database contains all the completely sequenced bacterial and viral genomes according to NCBI RefSeq. General properties of the genome DNA electrostatic potential profile and principles of its formation are revealed. This potential correlates with the GC content but does not correspond to it exactly and strongly depends on both the sequence arrangement and its context (flanking regions). Analysis of the promoter regions for bacterial and viral RNA polymerases revealed a correspondence between the scale of these proteins' physical properties and electrostatic profile patterns. We also discovered a direct correlation between the potential value and the binding frequency of RNA polymerase to DNA, supporting the idea of the role of electrostatics in these interactions. This matches a pronounced tendency of the promoter regions to possess higher values of the electrostatic potential.

Molecular dynamics simulations of pea (Pisum sativum) lectin structure with octyl glucoside detergents: the ligand interactions and dynamics.

PubMed

Konidala, Praveen; Niemeyer, Bernd

2007-07-01

The mitogenic pea (Pisum sativum) lectin is a legume protein of non-immunoglobulin nature capable of specific recognition of glucose derivatives without altering its structure. Molecular dynamics simulations were performed in a realistic environment to investigate the structure and interaction properties of pea lectin with various concentrations of n-octyl-beta-d-glucopyranoside (OG) detergent monomers distributed inside explicit solvent cell. In addition, the diffusion coefficients of the ligands (OG, Ca2+, Mn2+, and Cl-) and the water molecules were also reported. The structural flexibility of the lectin was conserved in all simulations. The self-assembly of OG monomers into a small micelle at the hydrophobic site of the lectin was noticed in the simulation with 20 OG monomers. The interaction energy analysis concludes that the lectin was appropriately termed an adaptive structure. One or rarely two binding sites were observed at an instant in each simulation that were electrostatically favoured for the OG to interact with the surface amino acid residues. Enhanced binding of OG to the pea lectin was quantified in the system containing only Ca2+ divalent ions. Interestingly, no binding was observed in the simulation without divalent ions. Furthermore, the lectin-ligand complex was stabilized by multiple hydrogen bonds and at least one water bridge. Finally, the work was also in accordance with the published work elsewhere that the simulations performed with different initial conditions and using higher nonbonded cutoffs for the van der Waals and electrostatic interactions provide more accurate information and clues than the single large simulation of the biomolecular system of interest.

Electrostatic potential calculation for biomolecules--creating a database of pre-calculated values reported on a per residue basis for all PDB protein structures.

PubMed

Rocchia, W; Neshich, G

2007-10-05

STING and Java Protein Dossier provide a collection of physical-chemical parameters, describing protein structure, stability, function, and interaction, considered one of the most comprehensive among the available protein databases of similar type. Particular attention in STING is paid to the electrostatic potential. It makes use of DelPhi, a well-known tool that calculates this physical-chemical quantity for biomolecules by solving the Poisson Boltzmann equation. In this paper, we describe a modification to the DelPhi program aimed at integrating it within the STING environment. We also outline how the "amino acid electrostatic potential" and the "surface amino acid electrostatic potential" are calculated (over all Protein Data Bank (PDB) content) and how the corresponding values are made searchable in STING_DB. In addition, we show that the STING and Java Protein Dossier are also capable of providing these particular parameter values for the analysis of protein structures modeled in computers or being experimentally solved, but not yet deposited in the PDB. Furthermore, we compare the calculated electrostatic potential values obtained by using the earlier version of DelPhi and those by STING, for the biologically relevant case of lysozyme-antibody interaction. Finally, we describe the STING capacity to make queries (at both residue and atomic levels) across the whole PDB, by looking at a specific case where the electrostatic potential parameter plays a crucial role in terms of a particular protein function, such as ligand binding. BlueStar STING is available at http://www.cbi.cnptia.embrapa.br.

Structure and spectroscopic investigations of a bi-dentate N‧-[(4-ethylphenyl)methylidene]-4-hydroxybenzohydrazide and its Co(II), Ni(II), Cu(II) and Cd(II) complexes: Insights relevant to biological properties

NASA Astrophysics Data System (ADS)

Gopal Reddy, N. B.; Krishna, P. Murali; Shantha Kumar, S. S.; Patil, Yogesh P.; Nethaji, Munirathinam

2017-06-01

The present paper describes the synthesis of novel ligand, N‧-[(4-ethylphenyl)methylidene]-4-hydroxy benzohydrazide (HL) and its Co(II), Ni(II), Cu(II) and Cd(II) complexes. The ligand (HL) crystallizes in orthorhombic lattice in P212121 space group with a = 7.9941 (7) Å, b = 11.6154 (10) Å, c = 15.2278 (13) Å, α = β = γ = 90°. Spectroscopic data gives the strong evidence that ligand is coordinated through azomethine nitrogen and enolic oxygen with metal ion. The DNA binding studies revealed that the complexes bind to CT-DNA via intercalation/electrostatic interaction. All the targeted compounds showed more pronounced DNA cleavage activity in the presence of H2O2 and also inhibit the growth of in vitro antibacterial activity against Gram-positive and Gram-negative bacteria.

Hexahomotrioxacalix[3]arene derivatives as ionophores for molecular recognition of dopamine, serotonin and phenylethylamine.

PubMed

Ni, Xin-Long; Rahman, Shofiur; Wang, Shi; Jin, Cheng-Cheng; Zeng, Xi; Hughes, David L; Redshaw, Carl; Yamato, Takehiko

2012-06-21

The lower rim functionalized hexahomotrioxacalix[3]arene derivatives cone-3 and cone-5 bearing three benzyl and three N,N-diethyl-2-aminoethoxy groups, respectively, were synthesized from triol 1. Their complexation with 2-(3,4-dihydroxyphenyl)ethylamine (dopamine), 5-hydroxytryptamine (serotonin), and 2-phenylethylamine (phenethylamine), which have biologically important activities, has been studied by (1)H-NMR spectroscopy. The chemical shifts of the aromatic protons of the host and guest molecules and the up-field shifts of the ethyl protons of the guest molecules strongly suggest the formation of inclusion complexes in solution. The formation of the host-guest complexes is assisted by a hydrogen bond and/or an electrostatic interaction between the host and ammonium ion (RNH(3)(+)) of the guest. The structures of receptors cone-3 and cone-5 have been determined by X-ray crystallography.

Computer simulations of dendrimer-polyelectrolyte complexes.

PubMed

Pandav, Gunja; Ganesan, Venkat

2014-08-28

We carry out a systematic analysis of static properties of the clusters formed by complexation between charged dendrimers and linear polyelectrolyte (LPE) chains in a dilute solution under good solvent conditions. We use single chain in mean-field simulations and analyze the structure of the clusters through radial distribution functions of the dendrimer, cluster size, and charge distributions. The effects of LPE length, charge ratio between LPE and dendrimer, the influence of salt concentration, and the dendrimer generation number are examined. Systems with short LPEs showed a reduced propensity for aggregation with dendrimers, leading to formation of smaller clusters. In contrast, larger dendrimers and longer LPEs lead to larger clusters with significant bridging. Increasing salt concentration was seen to reduce aggregation between dendrimers as a result of screening of electrostatic interactions. Generally, maximum complexation was observed in systems with an equal amount of net dendrimer and LPE charges, whereas either excess LPE or dendrimer concentrations resulted in reduced clustering between dendrimers.

The Effect of Salt on the Complex Coacervation of Vinyl Polyelectrolytes

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

Perry, Sarah; Li, Yue; Priftis, Dimitrios

2014-06-01

Complex coacervation is an electrostatically-driven phase separation phenomenon that is utilized in a wide range of everyday applications and is of great interest for the creation of self-assembled materials. Here, we utilized turbidity to characterize the effect of salt type on coacervate formation using two vinyl polyelectrolytes, poly(acrylic acid sodium salt) (pAA) and poly(allylamine hydrochloride) (pAH), as simple models for industrial and biological coacervates. We confirmed the dominant role of salt valence on the extent of coacervate formation, while demonstrating the presence of significant secondary effects, which can be described by Hofmeister-like behavior. These results revealed the importance of ion-specificmore » interactions, which are crucial for the informed design of coacervate-based materials for use in complex ionic environments, and can enable more detailed theoretical investigations on the role of subtle electrostatic and thermodynamic effects in complex coacervation.« less

Identification of molecular descriptors for design of novel Isoalloxazine derivatives as potential Acetylcholinesterase inhibitors against Alzheimer's disease.

PubMed

Gurung, Arun Bahadur; Aguan, Kripamoy; Mitra, Sivaprasad; Bhattacharjee, Atanu

2017-06-01

In Alzheimer's disease (AD), the level of Acetylcholine (ACh) neurotransmitter is reduced. Since Acetylcholinesterase (AChE) cleaves ACh, inhibitors of AChE are very much sought after for AD treatment. The side effects of current inhibitors necessitate development of newer AChE inhibitors. Isoalloxazine derivatives have proved to be promising (AChE) inhibitors. However, their structure-activity relationship studies have not been reported till date. In the present work, various quantitative structure-activity relationship (QSAR) building methods such as multiple linear regression (MLR), partial least squares ,and principal component regression were employed to derive 3D-QSAR models using steric and electrostatic field descriptors. Statistically significant model was obtained using MLR coupled with stepwise selection method having r 2  = .9405, cross validated r 2 (q 2 ) = .6683, and a high predictability (pred_r 2  = .6206 and standard error, pred_r 2 se = .2491). Steric and electrostatic contribution plot revealed three electrostatic fields E_496, E_386 and E_577 and one steric field S_60 contributing towards biological activity. A ligand-based 3D-pharmacophore model was generated consisting of eight pharmacophore features. Isoalloxazine derivatives were docked against human AChE, which revealed critical residues implicated in hydrogen bonds as well as hydrophobic interactions. The binding modes of docked complexes (AChE_IA1 and AChE_IA14) were validated by molecular dynamics simulation which showed their stable trajectories in terms of root mean square deviation and molecular mechanics/Poisson-Boltzmann surface area binding free energy analysis revealed key residues contributing significantly to overall binding energy. The present study may be useful in the design of more potent Isoalloxazine derivatives as AChE inhibitors.

The Kaposi Sarcoma Herpesvirus Latency-associated Nuclear Antigen DNA Binding Domain Dorsal Positive Electrostatic Patch Facilitates DNA Replication and Episome Persistence.

PubMed

Li, Shijun; Tan, Min; Juillard, Franceline; Ponnusamy, Rajesh; Correia, Bruno; Simas, J Pedro; Carrondo, Maria A; McVey, Colin E; Kaye, Kenneth M

2015-11-20

Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA binding surface, which is the site of BET protein binding. Here we investigate the functional role of the positive patch in LANA-mediated episome persistence. As expected, LANA mutants with alanine or glutamate substitutions in the central, peripheral, or lateral portions of the positive patch maintained the ability to bind DNA by EMSA. However, all of the substitution mutants were deficient for LANA DNA replication and episome maintenance. Mutation of the peripheral region generated the largest deficiencies. Despite these deficiencies, all positive patch mutants concentrated to dots along mitotic chromosomes in cells containing episomes, similar to LANA. The central and peripheral mutants, but not the lateral mutants, were reduced for BET protein interaction as assessed by co-immunoprecipitation. However, defects in BET protein binding were independent of episome maintenance function. Overall, the reductions in episome maintenance closely correlated with DNA replication deficiencies, suggesting that the replication defects account for the reduced episome persistence. Therefore, the electrostatic patch exerts a key role in LANA-mediated DNA replication and episome persistence and may act through a host cell partner(s) other than a BET protein or by inducing specific structures or complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

From the Biochemistry of Tubulin to the Biophysics of Microtubules

NASA Astrophysics Data System (ADS)

Brown, J. A.; Tuszyński, J. A.

2001-09-01

Mirotubules (MTs) are protein polymers of the cytoskeleton that once fully understood will provide a deeper understanding of many cell functions. Assembly dynamics with the characteristic dynamic instability phenomenon has been intensively investigated over the past two decades and several models have been developed which adequately describe this phenomenon. Since the tubulin structure was imaged by Nogales and Downing, the dipole has been calculated and also the charge distribution on the surface of the protein together with a hydrophobicity plot. However, it still remains to be seen how the dipole changes upon the conformational change due to GTP hydrolysis. Furthermore, the contribution of the carboxyl terminus to the dipolar and electrostatic properties has not been accounted for. Using the crystallographic data of Nogales and Downing, some properties of the new structure of tubulin were examined. The so called multi-tubulin hypothesis seems to be explained by the differences in the electrostatic potentials produced by various tubulin isotypes produced by only several amino-acid substitutions. Such small changes in the tubulin structure may render the MTs less susceptible to naturally occurring agents which would otherwise bind them and impair their function. The hypothesis of electrostatic binding between protofilaments seems to be well founded. The MT structure has been compared with the previous work, to comment on models of motor protein movement and to consider how isotype changes affect the electrostatic potential surrounding the MT. The nature of binding between the MT and motor proteins also seems to be electrostatic and can be used to explain the stepping of these motors along the MT surface. The overall picture emerging from these studies is that the tubulin's molecular structure and the ensuing microtubular architecture can provide a microscopic-level understanding of the biological function in the cell.

Electrostatics at the nanoscale.

PubMed

Walker, David A; Kowalczyk, Bartlomiej; de la Cruz, Monica Olvera; Grzybowski, Bartosz A

2011-04-01

Electrostatic forces are amongst the most versatile interactions to mediate the assembly of nanostructured materials. Depending on experimental conditions, these forces can be long- or short-ranged, can be either attractive or repulsive, and their directionality can be controlled by the shapes of the charged nano-objects. This Review is intended to serve as a primer for experimentalists curious about the fundamentals of nanoscale electrostatics and for theorists wishing to learn about recent experimental advances in the field. Accordingly, the first portion introduces the theoretical models of electrostatic double layers and derives electrostatic interaction potentials applicable to particles of different sizes and/or shapes and under different experimental conditions. This discussion is followed by the review of the key experimental systems in which electrostatic interactions are operative. Examples include electroactive and "switchable" nanoparticles, mixtures of charged nanoparticles, nanoparticle chains, sheets, coatings, crystals, and crystals-within-crystals. Applications of these and other structures in chemical sensing and amplification are also illustrated.

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

Marcianò, G.; Huang, D. T., E-mail: d.huang@beatson.gla.ac.uk

The Spt16–SSRP1 heterodimer is a histone chaperone that plays an important role in regulating chromatin assembly. Here, a crystal structure of the N-terminal domain of human Spt16 is presented and it is shown that this domain may contribute to histone binding. The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of humanmore » Spt16 is reported at a resolution of 1.84 Å. The structure adopts an aminopeptidase-like fold similar to those of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Spt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low-micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding.« less

Structural insights into Rhino-Deadlock complex for germline piRNA cluster specification.

PubMed

Yu, Bowen; Lin, Yu An; Parhad, Swapnil S; Jin, Zhaohui; Ma, Jinbiao; Theurkauf, William E; Zhang, Zz Zhao; Huang, Ying

2018-06-01

PIWI-interacting RNAs (piRNAs) silence transposons in germ cells to maintain genome stability and animal fertility. Rhino, a rapidly evolving heterochromatin protein 1 (HP1) family protein, binds Deadlock in a species-specific manner and so defines the piRNA-producing loci in the Drosophila genome. Here, we determine the crystal structures of Rhino-Deadlock complex in Drosophila melanogaster and simulans In both species, one Rhino binds the N-terminal helix-hairpin-helix motif of one Deadlock protein through a novel interface formed by the beta-sheet in the Rhino chromoshadow domain. Disrupting the interface leads to infertility and transposon hyperactivation in flies. Our structural and functional experiments indicate that electrostatic repulsion at the interaction interface causes cross-species incompatibility between the sibling species. By determining the molecular architecture of this piRNA-producing machinery, we discover a novel HP1-partner interacting mode that is crucial to piRNA biogenesis and transposon silencing. We thus explain the cross-species incompatibility of two sibling species at the molecular level. © 2018 The Authors.

Solar wind interaction with dusty plasmas produces instabilities and solitary structures

NASA Astrophysics Data System (ADS)

Saleem, H.; Ali, S.

2017-12-01

It is pointed out that the solar wind interaction with dusty magnetospheres of the planets can give rise to purely growing instabilities as well as nonlinear electric field structures. Linear dispersion relation of the low frequency electrostatic ion-acoustic wave (IAW) is modified in the presence of stationary dust and its frequency becomes larger than its frequency in usual electron ion plasma even if ion temperature is equal to the electron temperature. This dust-ion-acoustic wave (DIAW) either becomes a purely growing electrostatic instability or turns out to be the modified dust-ion-acoustic wave (mDIAW) depending upon the magnitude of shear flow scale length and its direction. Growth rate of shear flow-driven electrostatic instability in a plasma having negatively charged stationary dust is larger than the usual D'Angelo instability of electron-ion plasma. It is shown that shear modified dust ion acoustic wave (mDIAW) produces electrostatic solitons in the nonlinear regime. The fluid theory predicts the existence of electrostatic solitons in the dusty plasmas in those regions where the inhomogeneous solar wind flow is parallel to the planetary or cometary magnetic field lines. The amplitude and width of the solitary structure depends upon dust density and magnitude of shear in the flow. This is a general theoretical model which is applied to dusty plasma of Saturn's F-ring for illustration.

Emission shaping in fluorescent proteins: role of electrostatics and π-stacking.

PubMed

Park, Jae Woo; Rhee, Young Min

2016-02-07

For many decades, simulating the excited state properties of complex systems has been an intriguing but daunting task due to its high computational cost. Here, we apply molecular dynamics based techniques with interpolated potential energy surfaces toward calculating fluorescence spectra of the green fluorescent protein (GFP) and its variants in a statistically meaningful manner. With the GFP, we show that the diverse electrostatic tuning can shape the emission features in many different ways. By computationally modulating the electrostatic interactions between the chromophore phenoxy oxygen and its nearby residues, we demonstrate that we indeed can shift the emission to the blue or to the red side in a predictable manner. We rationalize the shifting effects of individual residues in the GFP based on the responses of both the adiabatic and the diabatic electronic states of the chromophore. We next exhibit that the yellow emitting variant, the Thr203Tyr mutant, generates changes in the electrostatic interactions and an additional π-stacking interaction. These combined effects indeed induce a red shift to emit the fluorescence into the yellow region. With the series of demonstrations, we suggest that our approach can provide sound rationales and useful insights in understanding different responses of various fluorescent complexes, which may be helpful in designing new light emitting proteins and other related systems in future studies.

Morphing hybrid honeycomb (MOHYCOMB) with in situ Poisson’s ratio modulation

NASA Astrophysics Data System (ADS)

Heath, Callum J. C.; Neville, Robin M.; Scarpa, Fabrizio; Bond, Ian P.; Potter, Kevin D.

2016-08-01

Electrostatic adhesion can be used as a means of reversible attachment. Through application of high voltage (~2 kV) across closely spaced parallel plate electrodes, significant shear stresses (11 kPa) can be generated. The highest levels of electrostatic holding force can be achieved through close contact of connection surfaces; this is facilitated by flexible electrodes which can conform to reduce air gaps. Cellular structures are comprised of thin walled elements, making them ideal host structures for electrostatic adhesive elements. The reversible adhesion provides control of the internal connectivity of the cellular structure, and determines the effective cell geometry. This would offer variable stiffness and control of the effective Poisson’s ratio of the global cellular array. Using copper-polyimide thin film laminates and PVDF thin film dielectrics, double lap shear electrostatic adhesive elements have been introduced to a cellular geometry. By activating different groups of reversible adhesive interfaces, the cellular array can assume four different cell configurations. A maximum stiffness modulation of 450% between the ‘All off’ and ‘All on’ cell morphologies has been demonstrated. This structure is also capable of in situ effective Poisson’s ratio variations, with the ability to switch between values of -0.45 and 0.54. Such a structure offers the potential for tuneable vibration absorption (due to its variable stiffness properties), or as a smart honeycomb with controllable curvature and is termed morphing hybrid honeycomb.

Comparative molecular field analysis of artemisinin derivatives: Ab initio versus semiempirical optimized structures

NASA Astrophysics Data System (ADS)

Tonmunphean, Somsak; Kokpol, Sirirat; Parasuk, Vudhichai; Wolschann, Peter; Winger, Rudolf H.; Liedl, Klaus R.; Rode, Bernd M.

1998-07-01

Based on the belief that structural optimization methods, producing structures more closely to the experimental ones, should give better, i.e. more relevant, steric fields and hence more predictive CoMFA models, comparative molecular field analyses of artemisinin derivatives were performed based on semiempirical AM1 and HF/3-21G optimized geometries. Using these optimized geometries, the CoMFA results derived from the HF/3-21G method are found to be usually but not drastically better than those from AM1. Additional calculations were performed to investigate the electrostatic field difference using the Gasteiger and Marsili charges, the electrostatic potential fit charges at the AM1 level, and the natural population analysis charges at the HF/3-21G level of theory. For the HF/3-21G optimized structures no difference in predictability was observed, whereas for AM1 optimized structures such differences were found. Interestingly, if ionic compounds are omitted, differences between the various HF/3-21G optimized structure models using these electrostatic fields were found.

Interactions of the α-subunits of heterotrimeric G-proteins with GPCRs, effectors and RGS proteins: a critical review and analysis of interacting surfaces, conformational shifts, structural diversity and electrostatic potentials.

PubMed

Baltoumas, Fotis A; Theodoropoulou, Margarita C; Hamodrakas, Stavros J

2013-06-01

G-protein coupled receptors (GPCRs) are one of the largest families of membrane receptors in eukaryotes. Heterotrimeric G-proteins, composed of α, β and γ subunits, are important molecular switches in the mediation of GPCR signaling. Receptor stimulation after the binding of a suitable ligand leads to G-protein heterotrimer activation and dissociation into the Gα subunit and Gβγ heterodimer. These subunits then interact with a large number of effectors, leading to several cell responses. We studied the interactions between Gα subunits and their binding partners, using information from structural, mutagenesis and Bioinformatics studies, and conducted a series of comparisons of sequence, structure, electrostatic properties and intermolecular energies among different Gα families and subfamilies. We identified a number of Gα surfaces that may, in several occasions, participate in interactions with receptors as well as effectors. The study of Gα interacting surfaces in terms of sequence, structure and electrostatic potential reveals features that may account for the Gα subunit's behavior towards its interacting partners. The electrostatic properties of the Gα subunits, which in some cases differ greatly not only between families but also between subfamilies, as well as the G-protein interacting surfaces of effectors and regulators of G-protein signaling (RGS) suggest that electrostatic complementarity may be an important factor in G-protein interactions. Energy calculations also support this notion. This information may be useful in future studies of G-protein interactions with GPCRs and effectors. Copyright © 2013 Elsevier Inc. All rights reserved.

Novel dimeric interface and electrostatic recognition in bacterial Cu,Zn superoxide dismutase

PubMed Central

Bourne, Yves; Redford, Susan M.; Steinman, Howard M.; Lepock, James R.; Tainer, John A.; Getzoff, Elizabeth D.

1996-01-01

Eukaryotic Cu,Zn superoxide dismutases (CuZnSODs) are antioxidant enzymes remarkable for their unusually stable β-barrel fold and dimer assembly, diffusion-limited catalysis, and electrostatic guidance of their free radical substrate. Point mutations of CuZnSOD cause the fatal human neurodegenerative disease amyotrophic lateral sclerosis. We determined and analyzed the first crystallographic structure (to our knowledge) for CuZnSOD from a prokaryote, Photobacterium leiognathi, a luminescent symbiont of Leiognathid fish. This structure, exemplifying prokaryotic CuZnSODs, shares the active-site ligand geometry and the topology of the Greek key β-barrel common to the eukaryotic CuZnSODs. However, the β-barrel elements recruited to form the dimer interface, the strategy used to forge the channel for electrostatic recognition of superoxide radical, and the connectivity of the intrasubunit disulfide bond in P. leiognathi CuZnSOD are discrete and strikingly dissimilar from those highly conserved in eukaryotic CuZnSODs. This new CuZnSOD structure broadens our understanding of structural features necessary and sufficient for CuZnSOD activity, highlights a hitherto unrecognized adaptability of the Greek key β-barrel building block in evolution, and reveals that prokaryotic and eukaryotic enzymes diverged from one primordial CuZnSOD and then converged to distinct dimeric enzymes with electrostatic substrate guidance. PMID:8917495

Surface structural ion adsorption modeling of competitive binding of oxyanions by metal (hydr)oxides

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

Hiemstra, T.; Riemsdijk, W.H. van

1999-02-01

An important challenge in surface complexation models (SCM) is to connect the molecular microscopic reality to macroscopic adsorption phenomena. This study elucidates the primary factor controlling the adsorption process by analyzing the adsorption and competition of PO{sub 4}, AsO{sub 4}, and SeO{sub 3}. The authors show that the structure of the surface-complex acting in the dominant electrostatic field can be ascertained as the primary controlling adsorption factor. The surface species of arsenate are identical with those of phosphate and the adsorption behavior is very similar. On the basis of the selenite adsorption, The authors show that the commonly used 1pKmore » models are incapable to incorporate in the adsorption modeling the correct bidentate binding mechanism found by spectroscopy. The use of the bidentate mechanism leads to a proton-oxyanion ratio and corresponding pH dependence that are too large. The inappropriate intrinsic charge attribution to the primary surface groups and the condensation of the inner sphere surface complex to a point charge are responsible for this behavior of commonly used 2pK models. Both key factors are differently defined in the charge distributed multi-site complexation (CD-MUSIC) model and are based in this model on a surface structural approach. The CD-MUSIC model can successfully describe the macroscopic adsorption phenomena using the surface speciation and binding mechanisms as found by spectroscopy. The model is also able to predict the anion competition well. The charge distribution in the interface is in agreement with the observed structure of surface complexes.« less

Multi-Scale Structure of Coacervates formed by Oppositely Charged Polyelectrolytes

NASA Astrophysics Data System (ADS)

Rubinstein, Michael

We develop a scaling model of coacervates formed by oppositely charged polyelectrolytes and demonstrate that they self-organize into multi-scale structures. The intramolecular electrostatic interactions in dilute polyanion or polycation solutions are characterized by the electrostatic blobs with size D- and D+ respectively, that repel neighboring blobs on the same chains with electrostatic energy on the order of thermal energy kT . After mixing, electrostatic intramolecular repulsion of polyelectrolytes with higher charged density, say polyanions, keeps these polyanions in coacervates aligned into stretched arrays of electrostatic blobs of size D-

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

Toczydlowska, Diana; Kedra-Krolik, Karolina; Nejbert, Krzysztof

The role of surface electrostatics on the reductive dissolution of iron (III) oxides is poorly understood, despite its importance in controlling the amount of mobilized iron. We report the potentiometric titration of the a; y -Fe2O3 oxides exposed to reductants and complexing ligands (Fe(II), ascorbate, oxalate, malonate). We monitored in situ surface and potentials, the ratio of mobilized ferric to ferrous ions, and periodically analyzed nanoparticle crystal structure using X-ray diffraction. We found that addition of Fe2+ ions produces a response consistent with the iron solubilityactivity curve, whereas the presence of ascorbate significantly decreases the amount of mobilized Fe(III) duemore » to reduction to Fe(II). In addition, XRD analysis proved that y-Fe2O3 particles remain structurally unchanged along the titration pathway despite iron cycling between aqueous and solid reservoirs. Our studies, suggest that the surface redoxactivity of iron oxides is primarily governed by the balance between Fe(III) and Fe(II) ions in aqueous phase, which may be easily altered by complexing and reducing agents.« less

Structure of the Complex between a Heparan Sulfate Octasaccharide and Mycobacterial Heparin-Binding Hemagglutinin.

PubMed

Huang, Teng-Yi; Irene, Deli; Zulueta, Medel Manuel L; Tai, Tzu-Jui; Lain, Shih-Han; Cheng, Cheng-Po; Tsai, Ping-Xi; Lin, Shu-Yi; Chen, Zhi-Geng; Ku, Chiao-Chu; Hsiao, Chwan-Deng; Chyan, Chia-Lin; Hung, Shang-Cheng

2017-04-03

Heparin-binding hemagglutinin (HBHA) is a 199 amino acid virulence factor at the envelope of Mycobacterium tuberculosis that contributes to latent tuberculosis. The binding of HBHA to respiratory epithelial cells, which leads to extrapulmonary dissemination of the pathogen, is mediated by cell-surface heparan sulfate (HS). We report the structural characterization of the HBHA/HS complex by NMR spectroscopy. To develop a model for the molecular recognition, the first chemically synthesized uniformly 13 C- and 15 N-labeled HS octasaccharide and a uniformly 13 C- and 15 N-labeled form of HBHA were prepared. Residues 180-195 at the C-terminal region of HBHA show large chemical shift perturbation upon association with the octasaccharide. Molecular dynamics simulations conforming to the multidimensional NMR data revealed key electrostatic and even hydrophobic interactions between the binding partners that may aid in the development of agents targeting the binding event. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure of the Human FANCL RING-Ube2T Complex Reveals Determinants of Cognate E3-E2 Selection

PubMed Central

Hodson, Charlotte; Purkiss, Andrew; Miles, Jennifer Anne; Walden, Helen

2014-01-01

Summary The combination of an E2 ubiquitin-conjugating enzyme with an E3 ubiquitin-ligase is essential for ubiquitin modification of a substrate. Moreover, the pairing dictates both the substrate choice and the modification type. The molecular details of generic E3-E2 interactions are well established. Nevertheless, the determinants of selective, specific E3-E2 recognition are not understood. There are ∼40 E2s and ∼600 E3s giving rise to a possible ∼24,000 E3-E2 pairs. Using the Fanconi Anemia pathway exclusive E3-E2 pair, FANCL-Ube2T, we report the atomic structure of the FANCL RING-Ube2T complex, revealing a specific and extensive network of additional electrostatic and hydrophobic interactions. Furthermore, we show that these specific interactions are required for selection of Ube2T over other E2s by FANCL. PMID:24389026

Evaluating the Free Energies of Solvation and Electronic Structures of Lithium-Ion Battery Electrolytes.

PubMed

Shakourian-Fard, Mehdi; Kamath, Ganesh; Sankaranarayanan, Subramanian K R S

2016-09-19

Adaptive biasing force molecular dynamics simulations and density functional theory calculations were performed to understand the interaction of Li(+) with pure carbonates and ethylene carbonate (EC)-based binary mixtures. The most favorable Li carbonate cluster configurations obtained from molecular dynamics simulations were subjected to detailed structural and thermochemistry calculations on the basis of the M06-2X/6-311++G(d,p) level of theory. We report the ranking of these electrolytes on the basis of the free energies of Li-ion solvation in carbonates and EC-based mixtures. A strong local tetrahedral order involving four carbonates around the Li(+) was seen in the first solvation shell. Thermochemistry calculations revealed that the enthalpy of solvation and the Gibbs free energy of solvation of the Li(+) ion with carbonates are negative and suggested the ion-carbonate complexation process to be exothermic and spontaneous. Natural bond orbital analysis indicated that Li(+) interacts with the lone pairs of electrons on the carbonyl oxygen atom in the primary solvation sphere. These interactions lead to an increase in the carbonyl (C=O) bond lengths, as evidenced by a redshift in the vibrational frequencies [ν(C=O)] and a decrease in the electron density values at the C=O bond critical points in the primary solvation sphere. Quantum theory of atoms in molecules, localized molecular orbital energy decomposition analysis (LMO-EDA), and noncovalent interaction plots revealed the electrostatic nature of the Li(+) ion interactions with the carbonyl oxygen atoms in these complexes. On the basis of LMO-EDA, the strongest attractive interaction in these complexes was found to be the electrostatic interaction followed by polarization, dispersion, and exchange interactions. Overall, our calculations predicted EC and a binary mixture of EC/dimethyl carbonate to be appropriate electrolytes for Li-ion batteries, which complies with experiments and other theoretical results. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Computational Methods for Biomolecular Electrostatics

PubMed Central

Dong, Feng; Olsen, Brett; Baker, Nathan A.

2008-01-01

An understanding of intermolecular interactions is essential for insight into how cells develop, operate, communicate and control their activities. Such interactions include several components: contributions from linear, angular, and torsional forces in covalent bonds, van der Waals forces, as well as electrostatics. Among the various components of molecular interactions, electrostatics are of special importance because of their long range and their influence on polar or charged molecules, including water, aqueous ions, and amino or nucleic acids, which are some of the primary components of living systems. Electrostatics, therefore, play important roles in determining the structure, motion and function of a wide range of biological molecules. This chapter presents a brief overview of electrostatic interactions in cellular systems with a particular focus on how computational tools can be used to investigate these types of interactions. PMID:17964951

Unraveling the Agglomeration Mechanism in Charged Block Copolymer and Surfactant Complexes

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

Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.

Here, we report a molecular dynamics simulation investigation of self-assembly and complex formation of charged-neutral double hydrophilic and hydrophobic-hydrophilic block copolymers (BCP) with oppositely charged surfactants. Furthermore, the structure of the surfactant micelles and the BCP aggregation on the micelle surface is systematically studied for five different BCP volume fractions that also mimics a reduction of the surfactant concentration. The local electrostatic interactions between the oppositely charged species encourage the formation of core-shell structures between the surfactant micelles where the surfactants form the cores and the charged blocks of the BCP form the corona. The emergent morphologies of these aggregatesmore » are contingent upon the nature of the BCP neutral blocks. The hydrophilic neutral blocks agglomerate with the micelles as hairy colloidal structures while the hydrophobic neutrals agglomerate in lamellar structures with the surfactant micelles. The distribution of counterion charges along the simulation box show a close-to-normal density distribution for the hydrophilic neutral blocks and a binodal distribution for hydrophobic neutral blocks. No specific surfactant concentration dependent scaling relation is observed as opposed to the simpler case of homo-polyelectrolytes.« less

Unraveling the Agglomeration Mechanism in Charged Block Copolymer and Surfactant Complexes

DOE PAGES

Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.; ...

2017-01-27

Here, we report a molecular dynamics simulation investigation of self-assembly and complex formation of charged-neutral double hydrophilic and hydrophobic-hydrophilic block copolymers (BCP) with oppositely charged surfactants. Furthermore, the structure of the surfactant micelles and the BCP aggregation on the micelle surface is systematically studied for five different BCP volume fractions that also mimics a reduction of the surfactant concentration. The local electrostatic interactions between the oppositely charged species encourage the formation of core-shell structures between the surfactant micelles where the surfactants form the cores and the charged blocks of the BCP form the corona. The emergent morphologies of these aggregatesmore » are contingent upon the nature of the BCP neutral blocks. The hydrophilic neutral blocks agglomerate with the micelles as hairy colloidal structures while the hydrophobic neutrals agglomerate in lamellar structures with the surfactant micelles. The distribution of counterion charges along the simulation box show a close-to-normal density distribution for the hydrophilic neutral blocks and a binodal distribution for hydrophobic neutral blocks. No specific surfactant concentration dependent scaling relation is observed as opposed to the simpler case of homo-polyelectrolytes.« less

Tunable recognition of the steroid α-face by adjacent π-electron density

PubMed Central

Friščić, T.; Lancaster, R. W.; Fábián, L.; Karamertzanis, P. G.

2010-01-01

We report a previously unknown recognition motif between the α-face of the steroid hydrocarbon backbone and π-electron-rich aromatic substrates. Our study is based on a systematic and comparative analysis of the solid-state complexation of four steroids with 24 aromatic molecules. By using the solid state as a medium for complexation, we circumvent solubility and solvent competition problems that are inherent to the liquid phase. Characterization is performed using powder and single crystal X-ray diffraction, infrared solid-state spectroscopy and is complemented by a comprehensive cocrystal structure prediction methodology that surpasses earlier computational approaches in terms of realism and complexity. Our combined experimental and theoretical approach reveals that the α⋯π stacking is of electrostatic origin and is highly dependent on the steroid backbone’s unsaturated and conjugated character. We demonstrate that the α⋯π stacking interaction can drive the assembly of molecules, in particular progesterone, into solid-state complexes without the need for additional strong interactions. It results in a marked difference in the solid-state complexation propensities of different steroids with aromatic molecules, suggesting a strong dependence of the steroid-binding affinity and even physicochemical properties on the steroid’s A-ring structure. Hence, the hydrocarbon part of the steroid is a potentially important variable in structure-activity relationships for establishing the binding and signaling properties of steroids, and in the manufacture of pharmaceutical cocrystals. PMID:20624985

Polyamidoamine-Decorated Nanodiamonds as a Hybrid Gene Delivery Vector and siRNA Structural Characterization at the Charged Interfaces.

PubMed

Lim, Dae Gon; Rajasekaran, Nirmal; Lee, Dukhee; Kim, Nam Ah; Jung, Hun Soon; Hong, Sungyoul; Shin, Young Kee; Kang, Eunah; Jeong, Seong Hoon

2017-09-20

Nanodiamonds have been discovered as a new exogenous material source in biomedical applications. As a new potent form of nanodiamond (ND), polyamidoamine-decorated nanodiamonds (PAMAM-NDs) were prepared for E7 or E6 oncoprotein-suppressing siRNA gene delivery for high risk human papillomavirus-induced cervical cancer, such as types 16 and 18. It is critical to understand the physicochemical properties of siRNA complexes immobilized on cationic solid ND surfaces in the aspect of biomolecular structural and conformational changes, as the new inert carbon material can be extended into the application of a gene delivery vector. A spectral study of siRNA/PAMAM-ND complexes using differential scanning calorimetry and circular dichroism spectroscopy proved that the hydrogen bonding and electrostatic interactions between siRNA and PAMAM-NDs decreased endothermic heat capacity. Moreover, siRNA/PAMAM-ND complexes showed low cell cytotoxicity and significant suppressing effects for forward target E6 and E7 oncogenic genes, proving functional and therapeutic efficacy. The cellular uptake of siRNA/PAMAM-ND complexes at 8 h was visualized by macropinocytes and direct endosomal escape of the siRNA/PAMAM-ND complexes. It is presumed that PAMAM-NDs provided a buffering cushion to adjust the pH and hard mechanical stress to escape endosomes. siRNA/PAMAM-ND complexes provide a potential organic/inorganic hybrid material source for gene delivery carriers.

DFT-based molecular modeling and vibrational study of the La(III) complex of 3,3'-(benzylidene)bis(4-hydroxycoumarin).

PubMed

Mihaylov, Tzvetan; Trendafilova, Natasha; Georgieva, Ivelina

2008-05-01

Molecular modeling of the La(III) complex of 3,3'-(benzylidene)bis(4-hydroxycoumarin) (PhDC) was performed using density functional theory (DFT) methods at B3LYP/6-31G(d) and BP86/TZP levels. Both Stuttgart-Dresden effective core potential and ZORA approximation were applied to the La(III) center. The electron density distribution and the nucleophilic centers of the deprotonated ligand PhDC(2-) in a solvent environment were estimated on the basis of Hirshfeld atomic charges, electrostatic potential values at the nuclei, and Nalewajski-Mrozek bond orders. In accordance with the empirical formula La(PhDC)(OH)(H(2)O), a chain structure of the complex was simulated by means of two types of molecular fragment: (1) two La(III) cations bound to one PhDC(2-) ligand, and (2) two PhDC(2-) ligands bound to one La(III) cation. Different orientations of PhDC(2-), OH(-) and H(2)O ligands in the La(III) complexes were investigated using 20 possible [La(PhDC(2-))(2)(OH)(H(2)O)](2-) fragments. Energy calculations predicted that the prism-like structure based on "tail-head" cis-LML2 type binding and stabilized via HO...HOH intramolecular hydrogen bonds is the most probable structure for the La(III) complex. The calculated vibrational spectrum of the lowest energy La(III) model fragment is in very good agreement with the experimental IR spectrum of the complex, supporting the suggested ligand binding mode to La(III) in a chain structure, namely, every PhDC(2-) interacts with two La(III) cations through both carbonylic and both hydroxylic oxygens, and every La(III) cation binds four oxygen atoms of two different PhDC(2-).

Crystal Structures of Covalent Complexes of [beta]-Lactam Antibiotics with Escherichia coli Penicillin-Binding Protein 5: Toward an Understanding of Antibiotic Specificity

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

Nicola, George; Tomberg, Joshua; Pratt, R.F.

Penicillin-binding proteins (PBPs) are the molecular targets for the widely used {beta}-lactam class of antibiotics, but how these compounds act at the molecular level is not fully understood. We have determined crystal structures of Escherichia coli PBP 5 as covalent complexes with imipenem, cloxacillin, and cefoxitin. These antibiotics exhibit very different second-order rates of acylation for the enzyme. In all three structures, there is excellent electron density for the central portion of the {beta}-lactam, but weak or absent density for the R1 or R2 side chains. Areas of contact between the antibiotics and PBP 5 do not correlate with themore » rates of acylation. The same is true for conformational changes, because although a shift of a loop leading to an electrostatic interaction between Arg248 and the {beta}-lactam carboxylate, which occurs completely with cefoxitin and partially with imipenem and is absent with cloxacillin, is consistent with the different rates of acylation, mutagenesis of Arg248 decreased the level of cefoxitin acylation only 2-fold. Together, these data suggest that structures of postcovalent complexes of PBP 5 are unlikely to be useful vehicles for the design of new covalent inhibitors of PBPs. Finally, superimposition of the imipenem-acylated complex with PBP 5 in complex with a boronic acid peptidomimetic shows that the position corresponding to the hydrolytic water molecule is occluded by the ring nitrogen of the {beta}-lactam. Because the ring nitrogen occupies a similar position in all three complexes, this supports the hypothesis that deacylation is blocked by the continued presence of the leaving group after opening of the {beta}-lactam ring.« less

Role of electrostatic interactions in determining the G-quadruplex structures

NASA Astrophysics Data System (ADS)

Lee, Jinkeong; Im, Haeri; Chong, Song-Ho; Ham, Sihyun

2018-02-01

We investigate the energetics of the antiparallel, hybrid and parallel type G-quadruplex structures of the human telomere DNA sequence. We find that both the conformational energy and solvation free energy of these structures are roughly inversely proportional to their radii of gyration. We rationalize this finding in terms of the dominance of the electrostatic contributions. We also show that the solvation free energy is more significant than the conformational energy in determining the G-quadruplex structures, which is in contrast to the canonical B-DNA structures. Our work will contribute to an understanding of the molecular mechanisms dictating various G-quadruplex topologies.

Bounding the electrostatic free energies associated with linear continuum models of molecular solvation.

PubMed

Bardhan, Jaydeep P; Knepley, Matthew G; Anitescu, Mihai

2009-03-14

The importance of electrostatic interactions in molecular biology has driven extensive research toward the development of accurate and efficient theoretical and computational models. Linear continuum electrostatic theory has been surprisingly successful, but the computational costs associated with solving the associated partial differential equations (PDEs) preclude the theory's use in most dynamical simulations. Modern generalized-Born models for electrostatics can reproduce PDE-based calculations to within a few percent and are extremely computationally efficient but do not always faithfully reproduce interactions between chemical groups. Recent work has shown that a boundary-integral-equation formulation of the PDE problem leads naturally to a new approach called boundary-integral-based electrostatics estimation (BIBEE) to approximate electrostatic interactions. In the present paper, we prove that the BIBEE method can be used to rigorously bound the actual continuum-theory electrostatic free energy. The bounds are validated using a set of more than 600 proteins. Detailed numerical results are presented for structures of the peptide met-enkephalin taken from a molecular-dynamics simulation. These bounds, in combination with our demonstration that the BIBEE methods accurately reproduce pairwise interactions, suggest a new approach toward building a highly accurate yet computationally tractable electrostatic model.

Bounding the electrostatic free energies associated with linear continuum models of molecular solvation

NASA Astrophysics Data System (ADS)

Bardhan, Jaydeep P.; Knepley, Matthew G.; Anitescu, Mihai

2009-03-01

The importance of electrostatic interactions in molecular biology has driven extensive research toward the development of accurate and efficient theoretical and computational models. Linear continuum electrostatic theory has been surprisingly successful, but the computational costs associated with solving the associated partial differential equations (PDEs) preclude the theory's use in most dynamical simulations. Modern generalized-Born models for electrostatics can reproduce PDE-based calculations to within a few percent and are extremely computationally efficient but do not always faithfully reproduce interactions between chemical groups. Recent work has shown that a boundary-integral-equation formulation of the PDE problem leads naturally to a new approach called boundary-integral-based electrostatics estimation (BIBEE) to approximate electrostatic interactions. In the present paper, we prove that the BIBEE method can be used to rigorously bound the actual continuum-theory electrostatic free energy. The bounds are validated using a set of more than 600 proteins. Detailed numerical results are presented for structures of the peptide met-enkephalin taken from a molecular-dynamics simulation. These bounds, in combination with our demonstration that the BIBEE methods accurately reproduce pairwise interactions, suggest a new approach toward building a highly accurate yet computationally tractable electrostatic model.

Electrostatically assembled dendrimer complex with a high-affinity protein binder for targeted gene delivery.

PubMed

Kim, Jong-Won; Lee, Joong-Jae; Choi, Joon Sig; Kim, Hak-Sung

2018-06-10

Although a variety of non-viral gene delivery systems have been developed, they still suffer from low efficiency and specificity. Herein, we present the assembly of a dendrimer complex comprising a DNA cargo and a targeting moiety as a new format for targeted gene delivery. A PAMAM dendrimer modified with histidine and arginine (HR-dendrimer) was used to enhance the endosomal escape and transfection efficiency. An EGFR-specific repebody, composed of leucine-rich repeat (LRR) modules, was employed as a targeting moiety. A polyanionic peptide was genetically fused to the repebody, followed by incubation with an HR-dendrimer and a DNA cargo to assemble the dendrimer complex through an electrostatic interaction. The resulting dendrimer complex was shown to deliver a DNA cargo with high efficiency in a receptor-specific manner. An analysis using a confocal microscope confirmed the internalization of the dendrimer complex and subsequent dissociation of a DNA cargo from the complex. The present approach can be broadly used in a targeted gene delivery in many areas. Copyright © 2018 Elsevier B.V. All rights reserved.

High-spin ribbons and antiferromagnetic ordering of a Mn(II)-biradical-Mn(II) complex.

PubMed

Fatila, Elisabeth M; Clérac, Rodolphe; Rouzières, Mathieu; Soldatov, Dmitriy V; Jennings, Michael; Preuss, Kathryn E

2013-09-11

A binuclear metal coordination complex of the first thiazyl-based biradical ligand 1 is reported (1 = 4,6-bis(1,2,3,5-dithiadiazolyl)pyrimidine; hfac =1,1,1,5,5,5,-hexafluoroacetylacetonato-). The Mn(hfac)2-biradical-Mn(hfac)2 complex 2 is a rare example of a discrete, molecular species employing a neutral bridging biradical ligand. It is soluble in common organic solvents and can be easily sublimed as a crystalline solid. Complex 2 has a spin ground state of S(T) = 4 resulting from antiferromagnetic coupling between the S(birad) = 1 biradical bridging ligand and two S(Mn) = 5/2 Mn(II) ions. Electrostatic contacts between atoms with large spin density promote a ferromagnetic arrangement of the moments of neighboring complexes in ribbon-like arrays. Weak antiferromagnetic coupling between these high-spin ribbons stabilizes an ordered antiferromagnetic ground state below 4.5 K. This is an unusual example of magnetic ordering in a molecular metal-radical complex, wherein the electrostatic contacts that direct the crystal packing are also responsible for providing an efficient exchange coupling pathway between molecules.

Molecular Basis for Phosphorylation-dependent SUMO Recognition by the DNA Repair Protein RAP80.

PubMed

Anamika; Spyracopoulos, Leo

2016-02-26

Recognition and repair of double-stranded DNA breaks (DSB) involves the targeted recruitment of BRCA tumor suppressors to damage foci through binding of both ubiquitin (Ub) and the Ub-like modifier SUMO. RAP80 is a component of the BRCA1 A complex, and plays a key role in the recruitment process through the binding of Lys(63)-linked poly-Ub chains by tandem Ub interacting motifs (UIM). RAP80 also contains a SUMO interacting motif (SIM) just upstream of the tandem UIMs that has been shown to specifically bind the SUMO-2 isoform. The RAP80 tandem UIMs and SIM function collectively for optimal recruitment of BRCA1 to DSBs, although the molecular basis of this process is not well understood. Using NMR spectroscopy, we demonstrate that the RAP80 SIM binds SUMO-2, and that both specificity and affinity are enhanced through phosphorylation of the canonical CK2 site within the SIM. The affinity increase results from an enhancement of electrostatic interactions between the phosphoserines of RAP80 and the SIM recognition module within SUMO-2. The NMR structure of the SUMO-2·phospho-RAP80 complex reveals that the molecular basis for SUMO-2 specificity is due to isoform-specific sequence differences in electrostatic SIM recognition modules. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

On the Selective Packaging of Genomic RNA by HIV-1.

PubMed

Comas-Garcia, Mauricio; Davis, Sean R; Rein, Alan

2016-09-12

Like other retroviruses, human immunodeficiency virus type 1 (HIV-1) selectively packages genomic RNA (gRNA) during virus assembly. However, in the absence of the gRNA, cellular messenger RNAs (mRNAs) are packaged. While the gRNA is selected because of its cis-acting packaging signal, the mechanism of this selection is not understood. The affinity of Gag (the viral structural protein) for cellular RNAs at physiological ionic strength is not much higher than that for the gRNA. However, binding to the gRNA is more salt-resistant, implying that it has a higher non-electrostatic component. We have previously studied the spacer 1 (SP1) region of Gag and showed that it can undergo a concentration-dependent conformational transition. We proposed that this transition represents the first step in assembly, i.e., the conversion of Gag to an assembly-ready state. To explain selective packaging of gRNA, we suggest here that binding of Gag to gRNA, with its high non-electrostatic component, triggers this conversion more readily than binding to other RNAs; thus we predict that a Gag-gRNA complex will nucleate particle assembly more efficiently than other Gag-RNA complexes. New data shows that among cellular mRNAs, those with long 3'-untranslated regions (UTR) are selectively packaged. It seems plausible that the 3'-UTR, a stretch of RNA not occupied by ribosomes, offers a favorable binding site for Gag.

Cationic polymers for DNA origami coating - examining their binding efficiency and tuning the enzymatic reaction rates.

PubMed

Kiviaho, Jenny K; Linko, Veikko; Ora, Ari; Tiainen, Tony; Järvihaavisto, Erika; Mikkilä, Joona; Tenhu, Heikki; Nonappa; Kostiainen, Mauri A

2016-06-02

DNA origamis are fully tailored, programmable, biocompatible and readily functionalizable nanostructures that provide an excellent foundation for the development of sophisticated drug-delivery systems. However, the DNA origami objects suffer from certain drawbacks such as low cell-transfection rates and low stability. A great deal of studies on polymer-based transfection agents, mainly focusing on polyplex formation and toxicity, exists. In this study, the electrostatic binding between a brick-like DNA origami and cationic block-copolymers was explored. The effect of the polymer structure on the binding was investigated and the toxicity of the polymer-origami complexes evaluated. The study shows that all of the analyzed polymers had a suitable binding efficiency irrespective of the block structure. It was also observed that the toxicity of polymer-origami complexes was insignificant at the biologically relevant concentration levels. Besides brick-like DNA origamis, tubular origami carriers equipped with enzymes were also coated with the polymers. By adjusting the amount of cationic polymers that cover the DNA structures, we showed that it is possible to control the enzyme kinetics of the complexes. This work gives a starting point for further development of biocompatible and effective polycation-based block copolymers that can be used in coating different DNA origami nanostructures for various bioapplications.

Transition from a beads-on-string to a spike structure in an electrified viscoelastic jet

NASA Astrophysics Data System (ADS)

Li, Fang; Yin, Xie-Yuan; Yin, Xie-Zhen

2017-02-01

A one-dimensional numerical simulation is performed to study the nonlinear behaviors of a perfectly conducting, slightly viscoelastic liquid jet under a large radial electric field. A singular spike structure different from a beads-on-string structure is detected. The electric field is found to be the key factor for the formation of spikes. The transition from a beads-on-string to a spike structure occurs at sufficiently large electric fields. Moreover, the transition occurs more easily for smaller wave numbers. Viscosity is found to suppress spikes while elasticity promotes them. The mechanism responsible for spike formation is further explored by examining the maximum radius of the jet in the beads-on-string case. The capillary and electrostatic forces prove to be dominant in droplets, and the transition takes place when the electrostatic force exceeds the capillary force. The self-similarity in spikes is discussed. Different from the transition moment, the inertial, electrostatic, and solvent viscous forces are important in a developed spike.

An electrostatic mechanism for Ca2+-mediated regulation of gap junction channels

PubMed Central

Bennett, Brad C.; Purdy, Michael D.; Baker, Kent A.; Acharya, Chayan; McIntire, William E.; Stevens, Raymond C.; Zhang, Qinghai; Harris, Andrew L.; Abagyan, Ruben; Yeager, Mark

2016-01-01

Gap junction channels mediate intercellular signalling that is crucial in tissue development, homeostasis and pathologic states such as cardiac arrhythmias, cancer and trauma. To explore the mechanism by which Ca2+ blocks intercellular communication during tissue injury, we determined the X-ray crystal structures of the human Cx26 gap junction channel with and without bound Ca2+. The two structures were nearly identical, ruling out both a large-scale structural change and a local steric constriction of the pore. Ca2+ coordination sites reside at the interfaces between adjacent subunits, near the entrance to the extracellular gap, where local, side chain conformational rearrangements enable Ca2+chelation. Computational analysis revealed that Ca2+-binding generates a positive electrostatic barrier that substantially inhibits permeation of cations such as K+ into the pore. Our results provide structural evidence for a unique mechanism of channel regulation: ionic conduction block via an electrostatic barrier rather than steric occlusion of the channel pore. PMID:26753910

Compliant displacement-multiplying apparatus for microelectromechanical systems

DOEpatents

Kota, Sridhar; Rodgers, M. Steven; Hetrick, Joel A.

2001-01-01

A pivotless compliant structure is disclosed that can be used to increase the geometric advantage or mechanical advantage of a microelectromechanical (MEM) actuator such as an electrostatic comb actuator, a capacitive-plate electrostatic actuator, or a thermal actuator. The compliant structure, based on a combination of interconnected flexible beams and cross-beams formed of one or more layers of polysilicon or silicon nitride, can provide a geometric advantage of from about 5:1 to about 60:1 to multiply a 0.25-3 .mu.m displacement provided by a short-stroke actuator so that such an actuator can be used to generate a displacement stroke of about 10-34 .mu.m to operate a ratchet-driven MEM device or a microengine. The compliant structure has less play than conventional displacement-multiplying devices based on lever arms and pivoting joints, and is expected to be more reliable than such devices. The compliant structure and an associated electrostatic or thermal actuator can be formed on a common substrate (e.g. silicon) using surface micromachining.

Molecular dynamics simulation of hepatitis C virus IRES IIId domain: structural behavior, electrostatic and energetic analysis.

PubMed

Golebiowski, Jérôme; Antonczak, Serge; Di-Giorgio, Audrey; Condom, Roger; Cabrol-Bass, Daniel

2004-02-01

The dynamic behavior of the HCV IRES IIId domain is analyzed by means of a 2.6-ns molecular dynamics simulation, starting from an NMR structure. The simulation is carried out in explicit water with Na+ counterions, and particle-mesh Ewald summation is used for the electrostatic interactions. In this work, we analyze selected patterns of the helix that are crucial for IRES activity and that could be considered as targets for the intervention of inhibitors, such as the hexanucleotide terminal loop (more particularly its three consecutive guanines) and the loop-E motif. The simulation has allowed us to analyze the dynamics of the loop substructure and has revealed a behavior among the guanine bases that might explain the different role of the third guanine of the GGG triplet upon molecular recognition. The accessibility of the loop-E motif and the loop major and minor groove is also examined, as well as the effect of Na+ or Mg2+ counterion within the simulation. The electrostatic analysis reveals several ion pockets, not discussed in the experimental structure. The positions of these ions are useful for locating specific electrostatic recognition sites for potential inhibitor binding.

Compact RF ion source for industrial electrostatic ion accelerator

NASA Astrophysics Data System (ADS)

Kwon, Hyeok-Jung; Park, Sae-Hoon; Kim, Dae-Il; Cho, Yong-Sub

2016-02-01

Korea Multi-purpose Accelerator Complex is developing a single-ended electrostatic ion accelerator to irradiate gaseous ions, such as hydrogen and nitrogen, on materials for industrial applications. ELV type high voltage power supply has been selected. Because of the limited space, electrical power, and robust operation, a 200 MHz RF ion source has been developed. In this paper, the accelerator system, test stand of the ion source, and its test results are described.

Compact RF ion source for industrial electrostatic ion accelerator.

PubMed

Kwon, Hyeok-Jung; Park, Sae-Hoon; Kim, Dae-Il; Cho, Yong-Sub

2016-02-01

Korea Multi-purpose Accelerator Complex is developing a single-ended electrostatic ion accelerator to irradiate gaseous ions, such as hydrogen and nitrogen, on materials for industrial applications. ELV type high voltage power supply has been selected. Because of the limited space, electrical power, and robust operation, a 200 MHz RF ion source has been developed. In this paper, the accelerator system, test stand of the ion source, and its test results are described.

Investigation of Singly Ionized Iodine Spectroscopy in Support of Electrostatic Propulsion Diagnostics Development

DTIC Science & Technology

2012-07-02

from complex user interactions due to the use of liquid lasing medium with finite lifetime. Solid state lasers such as titanium sapphire (Ti:Sapphire...transitions for laser -induced fluorescence of an accelerated atomic iodine singly charged ion (I+). While the second spectrum of iodine has been analyzed...diagnostics tools, such as laser -induced fluorescence (LIF), to examine the plasma acceleration within an electro-static plasma propulsion thruster. While

Growth, structure, Hirshfeld surface and spectroscopic properties of 2-amino-4-hydroxy-6-methylpyrimidinium-2,3-pyrazinedicorboxylate single crystal

NASA Astrophysics Data System (ADS)

Faizan, Mohd; Alam, Mohammad Jane; Afroz, Ziya; Rodrigues, Vítor Hugo Nunes; Ahmad, Shabbir

2018-03-01

The present work is focused on the crystal structure, vibrational spectroscopy and DFT calculations of hydrogen bonded 2,3-pyrazinedicorboxylic acid and 2-amino-4-hydroxy-6-methylpyrimidine (PDCA-.AHMP+) crystal. The crystal structure has been determined using single crystal X-ray diffraction analysis which shows that the crystal belongs to monoclinic space group P21/n. The PDCA-.AHMP+ crystal has been characterized by FTIR, FT-Raman and FT-NMR spectroscopic techniques. The FTIR and FT-Raman spectra of the complex have unique spectroscopic feature as compared with those of the starting material to confirm salt formation. The theoretical vibrational studies have been performed to understand the modes of the vibrations of asymmetric unit of the complex by DFT methods. Hirschfeld surface and 2D fingerprint plots analyses were carried out to investigate the intermolecular interactions and its contribution in the building of PDCA-.AHMP+ crystal. The experimental and simulated 13C and 1H NMR studies have assisted in structural analysis of PDCA-.AHMP+ crystal. The electronic spectroscopic properties of the complex were explored by the experimental as well as theoretical electronic spectra simulated using TD-DFT/IEF-PCM method at B3LYP/6-311++G (d,p) level of theory. In addition, frontier molecular orbitals, molecular electrostatic potential map (MEP) and nonlinear optical (NLO) properties using DFT method have been also presented.

Biomolecular electrostatics and solvation: a computational perspective

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

Ren, Pengyu; Chun, Jaehun; Thomas, Dennis G.

2012-11-01

An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. Thismore » review discusses the solvation of biomolecules with a computational biophysics view towards describing the phenomenon. While our main focus lies on the computational aspect of the models, we summarize the common characteristics of biomolecular solvation (e.g., solvent structure, polarization, ion binding, and nonpolar behavior) in order to provide reasonable backgrounds to understand the solvation models.« less

Electric Potential and Electric Field Imaging with Applications

NASA Technical Reports Server (NTRS)

Generazio, Ed

2016-01-01

The technology and techniques for remote quantitative imaging of electrostatic potentials and electrostatic fields in and around objects and in free space is presented. Electric field imaging (EFI) technology may be applied to characterize intrinsic or existing electric potentials and electric fields, or an externally generated electrostatic field may be used for (illuminating) volumes to be inspected with EFI. The baseline sensor technology, electric field sensor (e-sensor), and its construction, optional electric field generation (quasistatic generator), and current e-sensor enhancements (ephemeral e-sensor) are discussed. Demonstrations for structural, electronic, human, and memory applications are shown. This new EFI capability is demonstrated to reveal characterization of electric charge distribution, creating a new field of study that embraces areas of interest including electrostatic discharge mitigation, crime scene forensics, design and materials selection for advanced sensors, dielectric morphology of structures, inspection of containers, inspection for hidden objects, tether integrity, organic molecular memory, and medical diagnostic and treatment efficacy applications such as cardiac polarization wave propagation and electromyography imaging.

Electrostatic channeling in P. falciparum DHFR-TS: Brownian dynamics and Smoluchowski modeling.

PubMed

Metzger, Vincent T; Eun, Changsun; Kekenes-Huskey, Peter M; Huber, Gary; McCammon, J Andrew

2014-11-18

We perform Brownian dynamics simulations and Smoluchowski continuum modeling of the bifunctional Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (P. falciparum DHFR-TS) with the objective of understanding the electrostatic channeling of dihydrofolate generated at the TS active site to the DHFR active site. The results of Brownian dynamics simulations and Smoluchowski continuum modeling suggest that compared to Leishmania major DHFR-TS, P. falciparum DHFR-TS has a lower but significant electrostatic-mediated channeling efficiency (?15-25%) at physiological pH (7.0) and ionic strength (150 mM). We also find that removing the electric charges from key basic residues located between the DHFR and TS active sites significantly reduces the channeling efficiency of P. falciparum DHFR-TS. Although several protozoan DHFR-TS enzymes are known to have similar tertiary and quaternary structure, subtle differences in structure, active-site geometry, and charge distribution appear to influence both electrostatic-mediated and proximity-based substrate channeling.

Membrane protein properties revealed through data-rich electrostatics calculations

PubMed Central

Guerriero, Christopher J.; Brodsky, Jeffrey L.; Grabe, Michael

2015-01-01

SUMMARY The electrostatic properties of membrane proteins often reveal many of their key biophysical characteristics, such as ion channel selectivity and the stability of charged membrane-spanning segments. The Poisson-Boltzmann (PB) equation is the gold standard for calculating protein electrostatics, and the software APBSmem enables the solution of the PB equation in the presence of a membrane. Here, we describe significant advances to APBSmem including: full automation of system setup, per-residue energy decomposition, incorporation of PDB2PQR, calculation of membrane induced pKa shifts, calculation of non-polar energies, and command-line scripting for large scale calculations. We highlight these new features with calculations carried out on a number of membrane proteins, including the recently solved structure of the ion channel TRPV1 and a large survey of 1,614 membrane proteins of known structure. This survey provides a comprehensive list of residues with large electrostatic penalties for being embedded in the membrane potentially revealing interesting functional information. PMID:26118532

Biomolecular electrostatics and solvation: a computational perspective

PubMed Central

Ren, Pengyu; Chun, Jaehun; Thomas, Dennis G.; Schnieders, Michael J.; Marucho, Marcelo; Zhang, Jiajing; Baker, Nathan A.

2012-01-01

An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis, and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. This review discusses the solvation of biomolecules with a computational biophysics view towards describing the phenomenon. While our main focus lies on the computational aspect of the models, we provide an overview of the basic elements of biomolecular solvation (e.g., solvent structure, polarization, ion binding, and nonpolar behavior) in order to provide a background to understand the different types of solvation models. PMID:23217364

Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations.

PubMed

Marcoline, Frank V; Bethel, Neville; Guerriero, Christopher J; Brodsky, Jeffrey L; Grabe, Michael

2015-08-04

The electrostatic properties of membrane proteins often reveal many of their key biophysical characteristics, such as ion channel selectivity and the stability of charged membrane-spanning segments. The Poisson-Boltzmann (PB) equation is the gold standard for calculating protein electrostatics, and the software APBSmem enables the solution of the PB equation in the presence of a membrane. Here, we describe significant advances to APBSmem, including full automation of system setup, per-residue energy decomposition, incorporation of PDB2PQR, calculation of membrane-induced pKa shifts, calculation of non-polar energies, and command-line scripting for large-scale calculations. We highlight these new features with calculations carried out on a number of membrane proteins, including the recently solved structure of the ion channel TRPV1 and a large survey of 1,614 membrane proteins of known structure. This survey provides a comprehensive list of residues with large electrostatic penalties for being embedded in the membrane, potentially revealing interesting functional information. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biomolecular electrostatics and solvation: a computational perspective.

PubMed

Ren, Pengyu; Chun, Jaehun; Thomas, Dennis G; Schnieders, Michael J; Marucho, Marcelo; Zhang, Jiajing; Baker, Nathan A

2012-11-01

An understanding of molecular interactions is essential for insight into biological systems at the molecular scale. Among the various components of molecular interactions, electrostatics are of special importance because of their long-range nature and their influence on polar or charged molecules, including water, aqueous ions, proteins, nucleic acids, carbohydrates, and membrane lipids. In particular, robust models of electrostatic interactions are essential for understanding the solvation properties of biomolecules and the effects of solvation upon biomolecular folding, binding, enzyme catalysis, and dynamics. Electrostatics, therefore, are of central importance to understanding biomolecular structure and modeling interactions within and among biological molecules. This review discusses the solvation of biomolecules with a computational biophysics view toward describing the phenomenon. While our main focus lies on the computational aspect of the models, we provide an overview of the basic elements of biomolecular solvation (e.g. solvent structure, polarization, ion binding, and non-polar behavior) in order to provide a background to understand the different types of solvation models.

Effect of Base Sequence "Defects" on the Electrostatic Potential of Dissolved DNA

NASA Astrophysics Data System (ADS)

Adams, Scott V.; Wagner, Katrina; Kephart, Thomas S.; Edwards, Glenn

1997-11-01

An analytical model of the electrostatic potential surrounding dissolved DNA has been developed. The model consists of an all-atom, mathematically helical structure for DNA, in which the atoms are arranged in infinite lines of discrete point charges on concentric cylindrical surfaces. The surrounding solvent and counterions are treated with the Debye-Huckel approximation (Wagner et al., Biophysical Journal 73, 21-30, 1997). Variation in the electrostatic potential due to structural differences between A, B, and Z conformations and homopolymer base sequence is apparent. The most recent modification to the model exploits the principle of superposition to calculate the potential of DNA with a base sequence containing `defects.' That is, the base sequence is no longer uniform along the polymer. Differences between the potential of homopolymer DNA and the potential of DNA containing base `defects' are immediately obvious. These results may aid in understanding the role of electrostatics in base-sequence specificity exhibited by DNA-binding proteins.

Computer simulation of the active site of human serum cholinesterase

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

Kefang Jiao; Song Li; Zhengzheng Lu

1996-12-31

The first 3D-structure of acetylchelinesterase from Torpedo California electric organ (T.AChE) was published by JL. Sussman in 1991. We have simulated 3D-structure of human serum cholinesterase (H.BuChE) and the active site of H.BuChE. It is discovered by experiment that the residue of H.BuChE is still active site after a part of H.BuChE is cut. For example, the part of 21KD + 20KD is active site of H.BuChE. The 20KD as it is. Studies on these peptides by Hemelogy indicate that two active peptides have same negative electrostatic potential maps diagram. These negative electrostatic areas attached by acetyl choline with positivemore » electrostatic potency. We predict that 147...236 peptide of AChE could be active site because it was as 20KD as with negative electrostatic potential maps. We look forward to proving from other ones.« less

Improvement of energy conversion effectiveness and maximum output power of electrostatic induction-type MEMS energy harvesters by using symmetric comb-electrode structures

NASA Astrophysics Data System (ADS)

Honma, H.; Mitsuya, H.; Hashiguchi, G.; Fujita, H.; Toshiyoshi, H.

2018-06-01

We introduce symmetric comb-electrode structures for the electrostatic vibrational MEMS energy harvester to lower the electrostatic constraint force attributed to the built-in electret potential, thereby allowing the harvester device to operate in a small acceleration range of 0.05 g or lower (1 g  =  9.8 m s‑2). Given the same device structure, two different potentials for the electret are tested to experimentally confirm that the output induction current is enhanced 4.2 times by increasing the electret potential from  ‑60 V to  ‑250 V. At the same time, the harvester effectiveness has been improved to as high as 93%. The device is used to swiftly charge a 470 µF storage capacitor to 3.3 V in 120 s from small sinusoidal vibrations of 0.6 g at 124 Hz.

Helical Structure Determines Different Susceptibilities of dsDNA, dsRNA, and tsDNA to Counterion-Induced Condensation

PubMed Central

Kornyshev, Alexei A.; Leikin, Sergey

2013-01-01

Recent studies of counterion-induced condensation of nucleic acid helices into aggregates produced several puzzling observations. For instance, trivalent cobalt hexamine ions condensed double-stranded (ds) DNA oligomers but not their more highly charged dsRNA counterparts. Divalent alkaline earth metal ions condensed triple-stranded (ts) DNA oligomers but not dsDNA. Here we show that these counterintuitive experimental results can be rationalized within the electrostatic zipper model of interactions between molecules with helical charge motifs. We report statistical mechanical calculations that reveal dramatic and nontrivial interplay between the effects of helical structure and thermal fluctuations on electrostatic interaction between oligomeric nucleic acids. Combining predictions for oligomeric and much longer helices, we also interpret recent experimental studies of the role of counterion charge, structure, and chemistry. We argue that an electrostatic zipper attraction might be a major or even dominant force in nucleic acid condensation. PMID:23663846

Design, Fabrication and Levitation Experiments of a Micromachined Electrostatically Suspended Six-Axis Accelerometer

PubMed Central

Cui, Feng; Liu, Wu; Chen, Wenyuan; Zhang, Weiping; Wu, Xiaosheng

2011-01-01

A micromachined electrostatically suspended six-axis accelerometer, with a square plate as proof mass housed by a top stator and bottom stator, is presented. The device structure and related techniques concerning its operating principles, such as calculation of capacitances and electrostatic forces/moments, detection and levitation control of the proof mass, acceleration measurement, and structural parameters design, are described. Hybrid MEMS manufacturing techniques, including surface micromachining fabrication of thin film electrodes and interconnections, integration fabrication of thick nickel structures about 500 μm using UV-LIGA by successful removal of SU-8 photoresist mold, DRIE of silicon proof mass in thickness of 450 μm, microassembly and solder bonding, were employed to fabricate this prototype microdevice. A levitation experiment system for the fabricated microaccelerometer chip is introduced, and levitation results show that fast initial levitation within 10 ms and stable full suspension of the proof mass have been successfully demonstrated. PMID:22247662

Quantum beats in conductance oscillations in graphene-based asymmetric double velocity wells and electrostatic wells

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

Liu, Lei; Department of Medical Physics, Basic Medical College, Hebei Medical University, Shijiazhuang, Hebei 050017; Li, Yu-Xian

2014-01-14

The transport properties in graphene-based asymmetric double velocity well (Fermi velocity inside the well less than that outside the well) and electrostatic well structures are investigated using the transfer matrix method. The results show that quantum beats occur in the oscillations of the conductance for asymmetric double velocity wells. The beating effect can also be found in asymmetric double electrostatic wells, but only if the widths of the two wells are different. The beat frequency for the asymmetric double well is exactly equal to the frequency difference between the oscillation rates in two isolated single wells with the same structuresmore » as the individual wells in the double well structure. A qualitative interpretation is proposed based on the fact that the resonant levels depend upon the sizes of the quantum wells. The beating behavior can provide a new way to identify the symmetry of double well structures.« less

Towards predictive molecular dynamics simulations of DNA: electrostatics and solution/crystal environments

NASA Astrophysics Data System (ADS)

Babin, Volodymr; Baucom, Jason; Darden, Thomas; Sagui, Celeste

2006-03-01

We have investigated to what extend molecular dynamics (MD) simulatons can reproduce DNA sequence-specific features, given different electrostatic descriptions and different cell environments. For this purpose, we have carried out multiple unrestrained MD simulations of the duplex d(CCAACGTTGG)2. With respect to the electrostatic descriptions, two different force fields were studied: a traditional description based on atomic point charges and a polarizable force field. With respect to the cell environment, the difference between crystal and solution environments is emphasized, as well as the structural importance of divalent ions. By imposing the correct experimental unit cell environment, an initial configuration with two ideal B-DNA duplexes in the unit cell is shown to converge to the crystallographic structure. To the best of our knowledge, this provides the first example of a multiple nanosecond MD trajectory that shows and ideal structure converging to an experimental one, with a significant decay of the RMSD.

Stripline fast faraday cup for measuring GHz structure of ion beams

DOEpatents

Bogaty, John M.

1992-01-01

The Stripline Fast Faraday Cup is a device which is used to quantitatively and qualitatively measure gigahertz time structure characteristics of ion beams with energies up to at least 30 Mev per nucleon. A stripline geometry is employed in conjunction with an electrostatic screen and a Faraday cup to provide for analysis of the structural characteristics of an ion beam. The stripline geometry allows for a large reduction in the size of the instrument while the electrostatic screen permits measurements of the properties associated with low speed ion beams.

Ionic strength independence of charge distributions in solvation of biomolecules

NASA Astrophysics Data System (ADS)

Virtanen, J. J.; Sosnick, T. R.; Freed, K. F.

2014-12-01

Electrostatic forces enormously impact the structure, interactions, and function of biomolecules. We perform all-atom molecular dynamics simulations for 5 proteins and 5 RNAs to determine the dependence on ionic strength of the ion and water charge distributions surrounding the biomolecules, as well as the contributions of ions to the electrostatic free energy of interaction between the biomolecule and the surrounding salt solution (for a total of 40 different biomolecule/solvent combinations). Although water provides the dominant contribution to the charge density distribution and to the electrostatic potential even in 1M NaCl solutions, the contributions of water molecules and of ions to the total electrostatic interaction free energy with the solvated biomolecule are comparable. The electrostatic biomolecule/solvent interaction energies and the total charge distribution exhibit a remarkable insensitivity to salt concentrations over a huge range of salt concentrations (20 mM to 1M NaCl). The electrostatic potentials near the biomolecule's surface obtained from the MD simulations differ markedly, as expected, from the potentials predicted by continuum dielectric models, even though the total electrostatic interaction free energies are within 11% of each other.

Second-Sphere Effects in Dinuclear FeIIIZnII Hydrolase Biomimetics: Tuning Binding and Reactivity Properties.

PubMed

Camargo, Tiago Pacheco; Neves, Ademir; Peralta, Rosely A; Chaves, Cláudia; Maia, Elene C P; Lizarazo-Jaimes, Edgar H; Gomes, Dawidson A; Bortolotto, Tiago; Norberto, Douglas R; Terenzi, Hernán; Tierney, David L; Schenk, Gerhard

2018-01-02

Herein, we report the synthesis and characterization of two dinuclear Fe III Zn II complexes [Fe III Zn II LP1] (1) and [Fe III Zn II LP2] (2), in which LP1 and LP2 are conjugated systems containing one and two pyrene groups, respectively, connected via the diamine -HN(CH 2 ) 4 NH- spacer to the well-known N 5 O 2 -donor H 2 L ligand (H 2 L = 2-bis{[(2-pyridylmethyl)aminomethyl]-6-[(2-hydroxybenzyl)(2-pyridylmethyl)]aminomethyl}-4-methylphenol). The complex [Fe III Zn II L1] (3), in which H 2 L was modified to H 2 L1, with a carbonyl group attached to the terminal phenol group, was included in this study for comparison purposes. 1 Both complexes 1 and 2 were satisfactorily characterized in the solid state and in solution. Extended X-ray absorption fine structure data for 1 and 3 in an acetonitrile solution show that the multiply bridged structure seen in the solid state of 3 is retained in solution. Potentiometric and UV-vis titration of 1 and 2 show that electrostatic interaction between the protonated amino groups and coordinated water molecules significantly decreases the pK a of the iron(III)-bound water compared to those of 3. On the other hand, catalytic activity studies using 1 and 2 in the hydrolysis of the activated substrate bis(2,4-dinitrophenyl)phosphate (BDNPP) resulted in a significant increase in the association of the substrate (K ass ≅ 1/K M ) compared to that of 3 because of electrostatic and hydrophobic interactions between BDNPP and the side-chain diaminopyrene of the ligands H 2 LP1 and H 2 LP2. In addition, the introduction of the pyrene motifs in 1 and 2 enhanced their activity toward DNA and as effective antitumor drugs, although the biochemical mechanism of the latter effect is currently under investigation. These complexes represent interesting examples of how to promote an increase in the activity of traditional artificial metal nucleases by introducing second-coordination-sphere effects.

Molecular dynamics simulation of liquid structure for undercooled Zr-Nb alloys assisted with electrostatic levitation experiments

NASA Astrophysics Data System (ADS)

Yang, S. J.; Hu, L.; Wang, L.; Wei, B.

2018-06-01

The liquid structures of undercooled Zr90Nb10, Zr70Nb30 and Zr50Nb50 alloys were studied by molecular dynamics simulation combined with electrostatic levitation experiments. The densities of three alloys were measured by electrostatic levitation to modify the Zr-Nb potential functions by adjusting parameters in potential functions. In simulation, the atomic packing in Zr-Nb alloys was more ordered at lower temperatures. The Voronoi tessellation analyses indicated Nb-centered clusters were easier to form than Zr-centered clusters although the Nb content was less than 50%. The partial pair distribution functions showed that the interactions among Zr atoms are quite different to that among Nb atoms.

Protein extraction into the bicontinuous microemulsion phase of a Water/SDS/pentanol/dodecane winsor-III system: Effect on nanostructure and protein conformation

DOE PAGES

Hayes, Douglas G.; Ye, Ran; Dunlap, Rachel N.; ...

2017-09-07

Bicontinuous microemulsions (BμEs), consisting of water and oil nanodomains separated by surfactant monolayers of near-zero curvature, are potentially valuable systems for purification and delivery of biomolecules, for hosting multiphasic biochemical reactions, and as templating media for preparing nanomaterials. We formed Winsor-III systems by mixing aqueous protein and sodium dodecyl sulfate (SDS) solutions with dodecane and 1-pentanol (cosurfactant) to efficiently extract proteins into the middle (BμE) phase. Bovine serum albumin (BSA) and cytochrome c partitioned to the BμE phase at 64% and 81% efficiency, respectively, producing highly concentrated protein solutions (32 and 44 g L –1, respectively), through release of watermore » and oil from the BμEs. Circular dichroism spectroscopic analysis demonstrated that BSA underwent minor secondary structural changes upon incorporation into BμEs, while the secondary structure of cytochrome c and pepsin underwent major changes. Small-angle x-ray scattering (SAXS) results show that proteins promoted an increase of the interfacial fluidity and surface area per volume for the BμE surfactant monolayers, and that each protein uniquely altered self-assembly in the Winsor-III systems. Cytochrome c partitioned via electrostatic attractions between SDS and the protein’s positively-charged groups, residing near the surfactant head groups of BμE monolayers, where it decreased surfactant packing efficiency. BSA partitioned through formation of SDS-BSA complexes via hydrophobic and electrostatic attractive interactions. As the BSA-SDS ratio increased, complexes’ partitioning favored BμEs over the oil excess phase due to the increased hydrophilicity of the complexes. In conclusion, this study demonstrates the potential utility of BμEs to purify proteins and prepare nanostructured fluids possessing high protein concentration.« less

Protein extraction into the bicontinuous microemulsion phase of a Water/SDS/pentanol/dodecane winsor-III system: Effect on nanostructure and protein conformation

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

Hayes, Douglas G.; Ye, Ran; Dunlap, Rachel N.

Bicontinuous microemulsions (BμEs), consisting of water and oil nanodomains separated by surfactant monolayers of near-zero curvature, are potentially valuable systems for purification and delivery of biomolecules, for hosting multiphasic biochemical reactions, and as templating media for preparing nanomaterials. We formed Winsor-III systems by mixing aqueous protein and sodium dodecyl sulfate (SDS) solutions with dodecane and 1-pentanol (cosurfactant) to efficiently extract proteins into the middle (BμE) phase. Bovine serum albumin (BSA) and cytochrome c partitioned to the BμE phase at 64% and 81% efficiency, respectively, producing highly concentrated protein solutions (32 and 44 g L –1, respectively), through release of watermore » and oil from the BμEs. Circular dichroism spectroscopic analysis demonstrated that BSA underwent minor secondary structural changes upon incorporation into BμEs, while the secondary structure of cytochrome c and pepsin underwent major changes. Small-angle x-ray scattering (SAXS) results show that proteins promoted an increase of the interfacial fluidity and surface area per volume for the BμE surfactant monolayers, and that each protein uniquely altered self-assembly in the Winsor-III systems. Cytochrome c partitioned via electrostatic attractions between SDS and the protein’s positively-charged groups, residing near the surfactant head groups of BμE monolayers, where it decreased surfactant packing efficiency. BSA partitioned through formation of SDS-BSA complexes via hydrophobic and electrostatic attractive interactions. As the BSA-SDS ratio increased, complexes’ partitioning favored BμEs over the oil excess phase due to the increased hydrophilicity of the complexes. In conclusion, this study demonstrates the potential utility of BμEs to purify proteins and prepare nanostructured fluids possessing high protein concentration.« less

Screening of benzamidine-based thrombin inhibitors via a linear interaction energy in continuum electrostatics model

NASA Astrophysics Data System (ADS)

Nicolotti, Orazio; Giangreco, Ilenia; Miscioscia, Teresa Fabiola; Convertino, Marino; Leonetti, Francesco; Pisani, Leonardo; Carotti, Angelo

2010-02-01

A series of 27 benzamidine inhibitors covering a wide range of biological activity and chemical diversity was analysed to derive a Linear Interaction Energy in Continuum Electrostatics (LIECE) model for analysing the thrombin inhibitory activity. The main interactions occurring at the thrombin binding site and the preferred binding conformations of inhibitors were explicitly biased by including into the LIECE model 10 compounds extracted from X-ray solved thrombin-inhibitor complexes available from the Protein Data Bank (PDB). Supported by a robust statistics ( r 2 = 0.698; q 2 = 0.662), the LIECE model was successful in predicting the inhibitory activity for about 76% of compounds ( r ext 2 ≥ 0.600) from a larger external test set encompassing 88 known thrombin inhibitors and, more importantly, in retrieving, at high sensitivity and with better performance than docking and shape-based methods, active compounds from a thrombin combinatorial library of 10240 mimetic chemical products. The herein proposed LIECE model has the potential for successfully driving the design of novel thrombin inhibitors with benzamidine and/or benzamidine-like chemical structure.

Nanocube-based hematite photoanode produced in the presence of Na2HPO4 for efficient solar water splitting

NASA Astrophysics Data System (ADS)

Liu, Kan; Wang, Hongyan; Wu, Quanping; Zhao, Jun; Sun, Zhe; Xue, Song

2015-06-01

A thin film of α-Fe2O3 on FTO substrate has been synthesized from hydrothermal process in an aqueous solution of FeCl3 and Na2HPO4. A nanocube structure of α-Fe2O3 is observed within the formed hematite films and coated with phosphate ions on the surface. For comparison, another phosphate modified hematite film has been prepared by soaking the bare hematite film in Na2HPO4 solution. A negative electrostatic field can be built up on the surface of both phosphate modified hematite which will promote charge separation and extraction of photoexcited holes to the electrode surface. It is found that different types of phosphate complex exist in the hematite films, which has been determined by the isoelectric point (IEP) of the hematite films, and consequently influences the formation and strength of the electrostatic field. The effects of phosphate ions on the morphology, surface characteristics and the photoelectrochemical properties of the hematite thin films are investigated and the mechanism is proposed.

Dynamics of streaming instability with quantum correction

NASA Astrophysics Data System (ADS)

Goutam, H. P.; Karmakar, P. K.

2017-05-01

A modified quantum hydrodynamic model (m-QHD) is herein proposed on the basis of the Thomas-Fermi (TF) theory of many fermionic quantum systems to investigate the dynamics of electrostatic streaming instability modes in a complex (dusty) quantum plasma system. The newly formulated m-QHD, as an amelioration over the existing usual QHD, employs a dimensionality-dependent Bohmian quantum correction prefactor, γ = [(D-2)/3D], in the electron quantum dynamics, where D symbolizing the problem dimensionality under consideration. The normal mode analysis of the coupled structure equations reveals the excitation of two distinct streaming modes associated with the flowing ions (against electrons and dust) and the flowing dust particulates (against the electrons and ions). It is mainly shown that the γ-factor introduces a new source of stability and dispersive effects to the ion-streaming instability solely; but not to the dust counterparts. A non-trivial application of our investigation in electrostatic beam-plasma (flow-driven) coupled dynamics leading to the development of self-sustained intense electric current, and hence, of strong magnetic field in compact astrophysical objects (in dwarf-family stars) is summarily indicated.

Modeling uranium(VI) adsorption onto montmorillonite under varying carbonate concentrations: A surface complexation model accounting for the spillover effect on surface potential

NASA Astrophysics Data System (ADS)

Tournassat, C.; Tinnacher, R. M.; Grangeon, S.; Davis, J. A.

2018-01-01

The prediction of U(VI) adsorption onto montmorillonite clay is confounded by the complexities of: (1) the montmorillonite structure in terms of adsorption sites on basal and edge surfaces, and the complex interactions between the electrical double layers at these surfaces, and (2) U(VI) solution speciation, which can include cationic, anionic and neutral species. Previous U(VI)-montmorillonite adsorption and modeling studies have typically expanded classical surface complexation modeling approaches, initially developed for simple oxides, to include both cation exchange and surface complexation reactions. However, previous models have not taken into account the unique characteristics of electrostatic surface potentials that occur at montmorillonite edge sites, where the electrostatic surface potential of basal plane cation exchange sites influences the surface potential of neighboring edge sites ('spillover' effect). A series of U(VI) - Na-montmorillonite batch adsorption experiments was conducted as a function of pH, with variable U(VI), Ca, and dissolved carbonate concentrations. Based on the experimental data, a new type of surface complexation model (SCM) was developed for montmorillonite, that specifically accounts for the spillover effect using the edge surface speciation model by Tournassat et al. (2016a). The SCM allows for a prediction of U(VI) adsorption under varying chemical conditions with a minimum number of fitting parameters, not only for our own experimental results, but also for a number of published data sets. The model agreed well with many of these datasets without introducing a second site type or including the formation of ternary U(VI)-carbonato surface complexes. The model predictions were greatly impacted by utilizing analytical measurements of dissolved inorganic carbon (DIC) concentrations in individual sample solutions rather than assuming solution equilibration with a specific partial pressure of CO2, even when the gas phase was laboratory air. Because of strong aqueous U(VI)-carbonate solution complexes, the measurement of DIC concentrations was even important for systems set up in the 'absence' of CO2, due to low levels of CO2 contamination during the experiment.

Three-dimensional structure of the NLRP7 pyrin domain: insight into pyrin-pyrin-mediated effector domain signaling in innate immunity.

PubMed

Pinheiro, Anderson S; Proell, Martina; Eibl, Clarissa; Page, Rebecca; Schwarzenbacher, Robert; Peti, Wolfgang

2010-08-27

The innate immune system provides an initial line of defense against infection. Nucleotide-binding domain- and leucine-rich repeat-containing protein (NLR or (NOD-like)) receptors play a critical role in the innate immune response by surveying the cytoplasm for traces of intracellular invaders and endogenous stress signals. NLRs themselves are multi-domain proteins. Their N-terminal effector domains (typically a pyrin or caspase activation and recruitment domain) are responsible for driving downstream signaling and initiating the formation of inflammasomes, multi-component complexes necessary for cytokine activation. However, the currently available structures of NLR effector domains have not yet revealed the mechanism of their differential modes of interaction. Here, we report the structure and dynamics of the N-terminal pyrin domain of NLRP7 (NLRP7 PYD) obtained by NMR spectroscopy. The NLRP7 PYD adopts a six-alpha-helix bundle death domain fold. A comparison of conformational and dynamics features of the NLRP7 PYD with other PYDs showed distinct differences for helix alpha3 and loop alpha2-alpha3, which, in NLRP7, is stabilized by a strong hydrophobic cluster. Moreover, the NLRP7 and NLRP1 PYDs have different electrostatic surfaces. This is significant, because death domain signaling is driven by electrostatic contacts and stabilized by hydrophobic interactions. Thus, these results provide new insights into NLRP signaling and provide a first molecular understanding of inflammasome formation.

Electrostatic quadrupole array for focusing parallel beams of charged particles

DOEpatents

Brodowski, John

1982-11-23

An array of electrostatic quadrupoles, capable of providing strong electrostatic focusing simultaneously on multiple beams, is easily fabricated from a single array element comprising a support rod and multiple electrodes spaced at intervals along the rod. The rods are secured to four terminals which are isolated by only four insulators. This structure requires bias voltage to be supplied to only two terminals and eliminates the need for individual electrode bias and insulators, as well as increases life by eliminating beam plating of insulators.

Solution structure of the phosphoryl transfer complex between the cytoplasmic A domain of the mannitol transporter IIMannitol and HPr of the Escherichia coli phosphotransferase system.

PubMed

Cornilescu, Gabriel; Lee, Byeong Ryong; Cornilescu, Claudia C; Wang, Guangshun; Peterkofsky, Alan; Clore, G Marius

2002-11-01

The solution structure of the complex between the cytoplasmic A domain (IIA(Mtl)) of the mannitol transporter II(Mannitol) and the histidine-containing phosphocarrier protein (HPr) of the Escherichia coli phosphotransferase system has been solved by NMR, including the use of conjoined rigid body/torsion angle dynamics, and residual dipolar couplings, coupled with cross-validation, to permit accurate orientation of the two proteins. A convex surface on HPr, formed by helices 1 and 2, interacts with a complementary concave depression on the surface of IIA(Mtl) formed by helix 3, portions of helices 2 and 4, and beta-strands 2 and 3. The majority of intermolecular contacts are hydrophobic, with a small number of electrostatic interactions at the periphery of the interface. The active site histidines, His-15 of HPr and His-65 of IIA(Mtl), are in close spatial proximity, and a pentacoordinate phosphoryl transition state can be readily accommodated with no change in protein-protein orientation and only minimal perturbations of the backbone immediately adjacent to the histidines. Comparison with two previously solved structures of complexes of HPr with partner proteins of the phosphotransferase system, the N-terminal domain of enzyme I (EIN) and enzyme IIA(Glucose) (IIA(Glc)), reveals a number of common features despite the fact that EIN, IIA(Glc), and IIA(Mtl) bear no structural resemblance to one another. Thus, entirely different underlying structural elements can form binding surfaces for HPr that are similar in terms of both shape and residue composition. These structural comparisons illustrate the roles of surface and residue complementarity, redundancy, incremental build-up of specificity and conformational side chain plasticity in the formation of transient specific protein-protein complexes in signal transduction pathways.

Crystal structure of LGR4-Rspo1 complex: insights into the divergent mechanisms of ligand recognition by leucine-rich repeat G-protein-coupled receptors (LGRs).

PubMed

Xu, Jin-Gen; Huang, Chunfeng; Yang, Zhengfeng; Jin, Mengmeng; Fu, Panhan; Zhang, Ni; Luo, Jian; Li, Dali; Liu, Mingyao; Zhou, Yan; Zhu, Yongqun

2015-01-23

Leucine-rich repeat G-protein-coupled receptors (LGRs) are a unique class of G-protein-coupled receptors characterized by a large extracellular domain to recognize ligands and regulate many important developmental processes. Among the three groups of LGRs, group B members (LGR4-6) recognize R-spondin family proteins (Rspo1-4) to stimulate Wnt signaling. In this study, we successfully utilized the "hybrid leucine-rich repeat technique," which fused LGR4 with the hagfish VLR protein, to obtain two recombinant human LGR4 proteins, LGR415 and LGR49. We determined the crystal structures of ligand-free LGR415 and the LGR49-Rspo1 complex. LGR4 exhibits a twisted horseshoe-like structure. Rspo1 adopts a flat and β-fold architecture and is bound in the concave surface of LGR4 in the complex through electrostatic and hydrophobic interactions. All the Rspo1-binding residues are conserved in LGR4-6, suggesting that LGR4-6 bind R-spondins through an identical surface. Structural analysis of our LGR4-Rspo1 complex with the previously determined LGR4 and LGR5 structures revealed that the concave surface of LGR4 is the sole binding site for R-spondins, suggesting a one-site binding model of LGR4-6 in ligand recognition. The molecular mechanism of LGR4-6 is distinct from the two-step mechanism of group A receptors LGR1-3 and the multiple-interface binding model of group C receptors LGR7-8, suggesting LGRs utilize the divergent mechanisms for ligand recognition. Our structures, together with previous reports, provide a comprehensive understanding of the ligand recognition by LGRs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Extending Halogen-based Medicinal Chemistry to Proteins: IODO-INSULIN AS A CASE STUDY.

PubMed

El Hage, Krystel; Pandyarajan, Vijay; Phillips, Nelson B; Smith, Brian J; Menting, John G; Whittaker, Jonathan; Lawrence, Michael C; Meuwly, Markus; Weiss, Michael A

2016-12-30

Insulin, a protein critical for metabolic homeostasis, provides a classical model for protein design with application to human health. Recent efforts to improve its pharmaceutical formulation demonstrated that iodination of a conserved tyrosine (Tyr B26 ) enhances key properties of a rapid-acting clinical analog. Moreover, the broad utility of halogens in medicinal chemistry has motivated the use of hybrid quantum- and molecular-mechanical methods to study proteins. Here, we (i) undertook quantitative atomistic simulations of 3-[iodo-Tyr B26 ]insulin to predict its structural features, and (ii) tested these predictions by X-ray crystallography. Using an electrostatic model of the modified aromatic ring based on quantum chemistry, the calculations suggested that the analog, as a dimer and hexamer, exhibits subtle differences in aromatic-aromatic interactions at the dimer interface. Aromatic rings (Tyr B16 , Phe B24 , Phe B25 , 3-I-Tyr B26 , and their symmetry-related mates) at this interface adjust to enable packing of the hydrophobic iodine atoms within the core of each monomer. Strikingly, these features were observed in the crystal structure of a 3-[iodo-Tyr B26 ]insulin analog (determined as an R 6 zinc hexamer). Given that residues B24-B30 detach from the core on receptor binding, the environment of 3-I-Tyr B26 in a receptor complex must differ from that in the free hormone. Based on the recent structure of a "micro-receptor" complex, we predict that 3-I-Tyr B26 engages the receptor via directional halogen bonding and halogen-directed hydrogen bonding as follows: favorable electrostatic interactions exploiting, respectively, the halogen's electron-deficient σ-hole and electronegative equatorial band. Inspired by quantum chemistry and molecular dynamics, such "halogen engineering" promises to extend principles of medicinal chemistry to proteins. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

CFD-ACE+: a CAD system for simulation and modeling of MEMS

NASA Astrophysics Data System (ADS)

Stout, Phillip J.; Yang, H. Q.; Dionne, Paul; Leonard, Andy; Tan, Zhiqiang; Przekwas, Andrzej J.; Krishnan, Anantha

1999-03-01

Computer aided design (CAD) systems are a key to designing and manufacturing MEMS with higher performance/reliability, reduced costs, shorter prototyping cycles and improved time- to-market. One such system is CFD-ACE+MEMS, a modeling and simulation environment for MEMS which includes grid generation, data visualization, graphical problem setup, and coupled fluidic, thermal, mechanical, electrostatic, and magnetic physical models. The fluid model is a 3D multi- block, structured/unstructured/hybrid, pressure-based, implicit Navier-Stokes code with capabilities for multi- component diffusion, multi-species transport, multi-step gas phase chemical reactions, surface reactions, and multi-media conjugate heat transfer. The thermal model solves the total enthalpy from of the energy equation. The energy equation includes unsteady, convective, conductive, species energy, viscous dissipation, work, and radiation terms. The electrostatic model solves Poisson's equation. Both the finite volume method and the boundary element method (BEM) are available for solving Poisson's equation. The BEM method is useful for unbounded problems. The magnetic model solves for the vector magnetic potential from Maxwell's equations including eddy currents but neglecting displacement currents. The mechanical model is a finite element stress/deformation solver which has been coupled to the flow, heat, electrostatic, and magnetic calculations to study flow, thermal electrostatically, and magnetically included deformations of structures. The mechanical or structural model can accommodate elastic and plastic materials, can handle large non-linear displacements, and can model isotropic and anisotropic materials. The thermal- mechanical coupling involves the solution of the steady state Navier equation with thermoelastic deformation. The electrostatic-mechanical coupling is a calculation of the pressure force due to surface charge on the mechanical structure. Results of CFD-ACE+MEMS modeling of MEMS such as cantilever beams, accelerometers, and comb drives are discussed.

Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling

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

Lin, Su-Chang; Lo, Yu-Chih; Wu, Hao

2010-08-23

MyD88, IRAK4 and IRAK2 are critical signalling mediators of the TLR/IL1-R superfamily. Here we report the crystal structure of the MyD88-IRAK4-IRAK2 death domain (DD) complex, which surprisingly reveals a left-handed helical oligomer that consists of 6 MyD88, 4 IRAK4 and 4 IRAK2 DDs. Assembly of this helical signalling tower is hierarchical, in which MyD88 recruits IRAK4 and the MyD88-IRAK4 complex recruits the IRAK4 substrates IRAK2 or the related IRAK1. Formation of these Myddosome complexes brings the kinase domains of IRAKs into proximity for phosphorylation and activation. Composite binding sites are required for recruitment of the individual DDs in the complex,more » which are confirmed by mutagenesis and previously identified signalling mutations. Specificities in Myddosome formation are dictated by both molecular complementarity and correspondence of surface electrostatics. The MyD88-IRAK4-IRAK2 complex provides a template for Toll signalling in Drosophila and an elegant mechanism for versatile assembly and regulation of DD complexes in signal transduction.« less

Studies on N-picolinoyl-N‧-benzothioylhydrazide and its Zn(II) complex: Synthesis, structure, antibacterial activity, thermal analysis and DFT calculation

NASA Astrophysics Data System (ADS)

Kushawaha, S. K.; Dani, R. K.; Bharty, M. K.; Chaudhari, U. K.; Sharma, V. K.; Kharwar, R. N.; Singh, N. K.

2014-04-01

A new Zn(II) complex [Zn(pbth)2] (where Hpbth = N-picolinoyl-N‧-benzothioylhydrazide) has been synthesized and characterized by elemental analyses, IR, UV-Visible and single crystal X-ray data. The distorted octahedral complex [Zn(pbth)2] crystallizes in monoclinic system with space group C2/c and is stabilized by various types of inter and intramolecular extended hydrogen bonding providing supramolecular framework. The optimized molecular geometry of N-picolinoyl-N‧-benzothioylhydrazide (Hpbth) and the zinc complex in the ground state have been calculated by using the DFT method using B3LYP functional with 6-311 G(d,p){C,H,N,O,S}/Lanl2DZ basis set. The results of the optimized molecular geometry are presented and compared with the experimental X-ray diffraction data. In addition, quantum chemical calculations of Hpbth and the complex, molecular electrostatic potential (MEP), contour map and frontier molecular orbital analysis were performed. The solid state electrical conductivity and thermal behaviour (TGA) of the complex were investigated. The bioefficacy of the complex has been examined against the growth of bacteria in vitro to evaluate its anti-microbial potential.

An NMR-Based Structural Rationale for Contrasting Stoichiometry and Ligand Binding Site(s) in Fatty Acid-binding Proteins†

PubMed Central

He, Yan; Estephan, Rima; Yang, Xiaomin; Vela, Adriana; Wang, Hsin; Bernard, Cédric; Stark, Ruth E.

2011-01-01

Liver fatty acid-binding protein (LFABP) is a 14-kDa cytosolic polypeptide, differing from other family members in number of ligand binding sites, diversity of bound ligands, and transfer of fatty acid(s) to membranes primarily via aqueous diffusion rather than direct collisional interactions. Distinct two-dimensional 1H-15N NMR signals indicative of slowly exchanging LFABP assemblies formed during stepwise ligand titration were exploited, without solving the protein-ligand complex structures, to yield the stoichiometries for the bound ligands, their locations within the protein binding cavity, the sequence of ligand occupation, and the corresponding protein structural accommodations. Chemical shifts were monitored for wild-type LFABP and a R122L/S124A mutant in which electrostatic interactions viewed as essential to fatty acid binding were removed. For wild-type LFABP the results compared favorably with previous tertiary structures of oleate-bound wild-type LFABP in crystals and in solution: there are two oleates, one U-shaped ligand that positions the long hydrophobic chain deep within the cavity and another extended structure with the hydrophobic chain facing the cavity and the carboxylate group lying close to the protein surface. The NMR titration validated a prior hypothesis that the first oleate to enter the cavity occupies the internal protein site. In contrast, 1H/15N chemical shift changes supported only one liganded oleate for R122L/S124A LFABP, at an intermediate location within the protein cavity. A rationale based on protein sequence and electrostatics was developed to explain the stoichiometry and binding site trends for LFABPs and to put these findings into context within the larger protein family. PMID:21226535

Crystal structure of the DNA polymerase III β subunit (β-clamp) from the extremophile Deinococcus radiodurans.

PubMed

Niiranen, Laila; Lian, Kjersti; Johnson, Kenneth A; Moe, Elin

2015-02-27

Deinococcus radiodurans is an extremely radiation and desiccation resistant bacterium which can tolerate radiation doses up to 5,000 Grays without losing viability. We are studying the role of DNA repair and replication proteins for this unusual phenotype by a structural biology approach. The DNA polymerase III β subunit (β-clamp) acts as a sliding clamp on DNA, promoting the binding and processivity of many DNA-acting proteins, and here we report the crystal structure of D. radiodurans β-clamp (Drβ-clamp) at 2.0 Å resolution. The sequence verification process revealed that at the time of the study the gene encoding Drβ-clamp was wrongly annotated in the genome database, encoding a protein of 393 instead of 362 amino acids. The short protein was successfully expressed, purified and used for crystallisation purposes in complex with Cy5-labeled DNA. The structure, which was obtained from blue crystals, shows a typical ring-shaped bacterial β-clamp formed of two monomers, each with three domains of identical topology, but with no visible DNA in electron density. A visualisation of the electrostatic surface potential reveals a highly negatively charged outer surface while the inner surface and the dimer forming interface have a more even charge distribution. The structure of Drβ-clamp was determined to 2.0 Å resolution and shows an evenly distributed electrostatic surface charge on the DNA interacting side. We hypothesise that this charge distribution may facilitate efficient movement on encircled DNA and help ensure efficient DNA metabolism in D. radiodurans upon exposure to high doses of ionizing irradiation or desiccation.

Using Atomic Force Microscopy to Characterize the Conformational Properties of Proteins and Protein-DNA Complexes That Carry Out DNA Repair.

PubMed

LeBlanc, Sharonda; Wilkins, Hunter; Li, Zimeng; Kaur, Parminder; Wang, Hong; Erie, Dorothy A

2017-01-01

Atomic force microscopy (AFM) is a scanning probe technique that allows visualization of single biomolecules and complexes deposited on a surface with nanometer resolution. AFM is a powerful tool for characterizing protein-protein and protein-DNA interactions. It can be used to capture snapshots of protein-DNA solution dynamics, which in turn, enables the characterization of the conformational properties of transient protein-protein and protein-DNA interactions. With AFM, it is possible to determine the stoichiometries and binding affinities of protein-protein and protein-DNA associations, the specificity of proteins binding to specific sites on DNA, and the conformations of the complexes. We describe methods to prepare and deposit samples, including surface treatments for optimal depositions, and how to quantitatively analyze images. We also discuss a new electrostatic force imaging technique called DREEM, which allows the visualization of the path of DNA within proteins in protein-DNA complexes. Collectively, these methods facilitate the development of comprehensive models of DNA repair and provide a broader understanding of all protein-protein and protein-nucleic acid interactions. The structural details gleaned from analysis of AFM images coupled with biochemistry provide vital information toward establishing the structure-function relationships that govern DNA repair processes. © 2017 Elsevier Inc. All rights reserved.

Role of second-sphere coordination in anion binding: Synthesis, characterization and X-ray structure of hexaamminecobalt(III) chloride hydrogen phthalate trihydrate and sodium hexaamminecobalt(III) benzoate monohydrate

NASA Astrophysics Data System (ADS)

Sharma, Raj Pal; Bala, Ritu; Sharma, Rajni; Kariuki, B. M.; Rychlewska, Urszula; Warżajtis, Beata

2005-06-01

In an effort to utilize [Co(NH 3) 6] 3+cation as a new host for carboxylate ions, orange coloured crystalline solids of composition [Co(NH 3) 6]Cl(C 8H 5O 4) 2·3H 2O ( 1) and Na[Co(NH 3) 6](C 7H 5O 2) 4·H 2O ( 2) were obtained by reacting hot aqueous solutions of hexaamminecobalt(III) chloride with potassium hydrogen phthalate and sodium benzoate in 1:3 molar ratio, respectively. The title complex salts were characterized by elemental analyses and spectroscopic studies (IR, UV/Visible and NMR). Single crystal X-ray structure determinations revealed the formation of second-sphere coordination complexes based on hydrogen bond interactions. In complex salt 1 only two out of three ionisable chloride ions present in [Co(NH 3) 6]Cl 3 were replaced by two CHO4- ions whereas in complex salt 2 all the three ionisable chloride ions present in [Co(NH 3) 6]Cl 3 were replaced and the final product was an adduct with another mole of sodium benzoate in solid state. The crystal lattice is stabilized by electrostatic forces of attraction and predominantly N-H⋯O interactions.

The Stiffness Variation of a Micro-Ring Driven by a Traveling Piecewise-Electrode

PubMed Central

Li, Yingjie; Yu, Tao; Hu, Yuh-Chung

2014-01-01

In the practice of electrostatically actuated micro devices; the electrostatic force is implemented by sequentially actuated piecewise-electrodes which result in a traveling distributed electrostatic force. However; such force was modeled as a traveling concentrated electrostatic force in literatures. This article; for the first time; presents an analytical study on the stiffness variation of microstructures driven by a traveling piecewise electrode. The analytical model is based on the theory of shallow shell and uniform electrical field. The traveling electrode not only applies electrostatic force on the circular-ring but also alters its dynamical characteristics via the negative electrostatic stiffness. It is known that; when a structure is subjected to a traveling constant force; its natural mode will be resonated as the traveling speed approaches certain critical speeds; and each natural mode refers to exactly one critical speed. However; for the case of a traveling electrostatic force; the number of critical speeds is more than that of the natural modes. This is due to the fact that the traveling electrostatic force makes the resonant frequencies of the forward and backward traveling waves of the circular-ring different. Furthermore; the resonance and stability can be independently controlled by the length of the traveling electrode; though the driving voltage and traveling speed of the electrostatic force alter the dynamics and stabilities of microstructures. This paper extends the fundamental insights into the electromechanical behavior of microstructures driven by electrostatic forces as well as the future development of MEMS/NEMS devices with electrostatic actuation and sensing. PMID:25230308

The stiffness variation of a micro-ring driven by a traveling piecewise-electrode.

PubMed

Li, Yingjie; Yu, Tao; Hu, Yuh-Chung

2014-09-16

In the practice of electrostatically actuated micro devices; the electrostatic force is implemented by sequentially actuated piecewise-electrodes which result in a traveling distributed electrostatic force. However; such force was modeled as a traveling concentrated electrostatic force in literatures. This article; for the first time; presents an analytical study on the stiffness variation of microstructures driven by a traveling piecewise electrode. The analytical model is based on the theory of shallow shell and uniform electrical field. The traveling electrode not only applies electrostatic force on the circular-ring but also alters its dynamical characteristics via the negative electrostatic stiffness. It is known that; when a structure is subjected to a traveling constant force; its natural mode will be resonated as the traveling speed approaches certain critical speeds; and each natural mode refers to exactly one critical speed. However; for the case of a traveling electrostatic force; the number of critical speeds is more than that of the natural modes. This is due to the fact that the traveling electrostatic force makes the resonant frequencies of the forward and backward traveling waves of the circular-ring different. Furthermore; the resonance and stability can be independently controlled by the length of the traveling electrode; though the driving voltage and traveling speed of the electrostatic force alter the dynamics and stabilities of microstructures. This paper extends the fundamental insights into the electromechanical behavior of microstructures driven by electrostatic forces as well as the future development of MEMS/NEMS devices with electrostatic actuation and sensing.

Charge Inversion by Electrostatic Complexation: Molecular Dynamics Simulations

NASA Astrophysics Data System (ADS)

Faraudo, Jordi; Travesset, Alex

2007-03-01

Ions near interfaces play an important role in many biological and physico-chemical processes and exhibit a fascinating diverse range of phenomena. A relevant example is charge inversion, where interfacial charges attract counterions in excess of their own nominal charge, thus leading to an inversion of the sign of the interfacial charge. In this work, we argue that in the case of amphiphilic interfaces, charge inversion can be generated by complexation, that is, electrostatic complexes containing several counterions bound to amphiphilic molecules. The formation of these complexes require the presence at the interface of groups with conformational degrees of freedom with many electronegative atoms. We illustrate this mechanism by analyzing all atomic molecular dynamics simulations of a DMPA (Dimirystoil-Phosphatidic acid) phospholipid monolayer in contact with divalent counterions. The results are found to be in agreement with recent experimental results on Langmuir monolayers. We also discuss the implications for biological systems, as Phosphatidic acid is emerging as a key signaling phospholipid.

Optical sample-position sensing for electrostatic levitation

NASA Technical Reports Server (NTRS)

Sridharan, G.; Chung, S.; Elleman, D.; Whim, W. K.

1989-01-01

A comparative study is conducted for optical position-sensing techniques applicable to micro-G conditions sample-levitation systems. CCD sensors are compared with one- and two-dimensional position detectors used in electrostatic particle levitation. In principle, the CCD camera method can be improved from current resolution levels of 200 microns through the incorporation of a higher-pixel device and more complex digital signal processor interface. Nevertheless, the one-dimensional position detectors exhibited superior, better-than-one-micron resolution.

Insight to the Interaction of the Dihydrolipoamide Acetyltransferase (E2) Core with the Peripheral Components in the Escherichia coli Pyruvate Dehydrogenase Complex via Multifaceted Structural Approaches*

PubMed Central

Chandrasekhar, Krishnamoorthy; Wang, Junjie; Arjunan, Palaniappa; Sax, Martin; Park, Yun-Hee; Nemeria, Natalia S.; Kumaran, Sowmini; Song, Jaeyoung; Jordan, Frank; Furey, William

2013-01-01

Multifaceted structural approaches were undertaken to investigate interaction of the E2 component with E3 and E1 components from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), as a representative of the PDHc from Gram-negative bacteria. The crystal structure of E3 at 2.5 Å resolution reveals similarity to other E3 structures and was an important starting point for understanding interaction surfaces between E3 and E2. Biochemical studies revealed that R129E-E2 and R150E-E2 substitutions in the peripheral subunit-binding domain (PSBD) of E2 greatly diminished PDHc activity, affected interactions with E3 and E1 components, and affected reductive acetylation of E2. Because crystal structures are unavailable for any complete E2-containing complexes, peptide-specific hydrogen/deuterium exchange mass spectrometry was used to identify loci of interactions between 3-lipoyl E2 and E3. Two peptides from the PSBD, including Arg-129, and three peptides from E3 displayed statistically significant reductions in deuterium uptake resulting from interaction between E3 and E2. Of the peptides identified on E3, two were from the catalytic site, and the third was from the interface domain, which for all known E3 structures is believed to interact with the PSBD. NMR clearly demonstrates that there is no change in the lipoyl domain structure on complexation with E3. This is the first instance where the entire wild-type E2 component was employed to understand interactions with E3. A model for PSBD-E3 binding was independently constructed and found to be consistent with the importance of Arg-129, as well as revealing other electrostatic interactions likely stabilizing this complex. PMID:23580650

Insight to the interaction of the dihydrolipoamide acetyltransferase (E2) core with the peripheral components in the Escherichia coli pyruvate dehydrogenase complex via multifaceted structural approaches.

PubMed

Chandrasekhar, Krishnamoorthy; Wang, Junjie; Arjunan, Palaniappa; Sax, Martin; Park, Yun-Hee; Nemeria, Natalia S; Kumaran, Sowmini; Song, Jaeyoung; Jordan, Frank; Furey, William

2013-05-24

Multifaceted structural approaches were undertaken to investigate interaction of the E2 component with E3 and E1 components from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc), as a representative of the PDHc from Gram-negative bacteria. The crystal structure of E3 at 2.5 Å resolution reveals similarity to other E3 structures and was an important starting point for understanding interaction surfaces between E3 and E2. Biochemical studies revealed that R129E-E2 and R150E-E2 substitutions in the peripheral subunit-binding domain (PSBD) of E2 greatly diminished PDHc activity, affected interactions with E3 and E1 components, and affected reductive acetylation of E2. Because crystal structures are unavailable for any complete E2-containing complexes, peptide-specific hydrogen/deuterium exchange mass spectrometry was used to identify loci of interactions between 3-lipoyl E2 and E3. Two peptides from the PSBD, including Arg-129, and three peptides from E3 displayed statistically significant reductions in deuterium uptake resulting from interaction between E3 and E2. Of the peptides identified on E3, two were from the catalytic site, and the third was from the interface domain, which for all known E3 structures is believed to interact with the PSBD. NMR clearly demonstrates that there is no change in the lipoyl domain structure on complexation with E3. This is the first instance where the entire wild-type E2 component was employed to understand interactions with E3. A model for PSBD-E3 binding was independently constructed and found to be consistent with the importance of Arg-129, as well as revealing other electrostatic interactions likely stabilizing this complex.

Effect of polarization on the stability of a helix dimer

NASA Astrophysics Data System (ADS)

Wang, Xing Y.; Zhang, John Z. H.

2011-01-01

Molecular dynamics (MD) simulations have been carried out to study helix-helix interaction using both standard AMBER and polarized force fields. Comparison of the two simulations shows that electrostatic polarization of intra-protein hydrogen bonds plays a significant role in stabilizing the structure of helix dimer. This stabilizing effect is clearly demonstrated by examining the monomer structure, helix crossing angle and stability of backbone hydrogen bonds under AMBER and PPC. Since reliable prediction of protein-protein structure is a significant challenge, the current study should help shed light on the importance of electrostatic polarization of protein in helix-helix interaction and helix bundle structures.

Structure of the Escherichia coli phosphonate binding protein PhnD and rationally optimized phosphonate biosensors.

PubMed

Alicea, Ismael; Marvin, Jonathan S; Miklos, Aleksandr E; Ellington, Andrew D; Looger, Loren L; Schreiter, Eric R

2011-12-02

The phnD gene of Escherichia coli encodes the periplasmic binding protein of the phosphonate (Pn) uptake and utilization pathway. We have crystallized and determined structures of E. coli PhnD (EcPhnD) in the absence of ligand and in complex with the environmentally abundant 2-aminoethylphosphonate (2AEP). Similar to other bacterial periplasmic binding proteins, 2AEP binds near the center of mass of EcPhnD in a cleft formed between two lobes. Comparison of the open, unliganded structure with the closed 2AEP-bound structure shows that the two lobes pivot around a hinge by ~70° between the two states. Extensive hydrogen bonding and electrostatic interactions stabilize 2AEP, which binds to EcPhnD with low nanomolar affinity. These structures provide insight into Pn uptake by bacteria and facilitated the rational design of high signal-to-noise Pn biosensors based on both coupled small-molecule dyes and autocatalytic fluorescent proteins. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structure of the Escherichia coli Phosphonate Binding Protein PhnD and Rationally Optimized Phosphonate Biosensors

PubMed Central

Alicea, Ismael; Marvin, Jonathan S.; Miklos, Aleksandr E.; Ellington, Andrew D.; Looger, Loren L.; Schreiter, Eric R.

2012-01-01

The phnD gene of Escherichia coli encodes the periplasmic binding protein of the phosphonate uptake and utilization pathway. We have crystallized and determined structures of E. coli PhnD (EcPhnD) in the absence of ligand and in complex with the environmentally abundant 2-aminoethylphosphonate (2AEP). Similar to other bacterial periplasmic binding proteins, 2AEP binds near the center of mass of EcPhnD in a cleft formed between two lobes. Comparison of the open, unliganded structure with the closed 2AEP-bound structure shows that the two lobes pivot around a hinge by ~70° between the two states. Extensive hydrogen bonding and electrostatic interactions stabilize 2AEP, which binds to EcPhnD with low nanomolar affinity. These structures provide insight into phosphonate uptake by bacteria and facilitated the rational design of high signal-to-noise phosphonate biosensors based both on coupled small molecule dyes and autocatalytic fluorescent proteins. PMID:22019591

Analysis of Structural MtrC Models Based on Homology with the Crystal Structure of MtrF

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

Edwards, Marcus; Fredrickson, Jim K.; Zachara, John M.

2012-12-01

The outer-membrane decahaem cytochrome MtrC is part of the transmembrane MtrCAB complex required for mineral respiration by Shewanella oneidensis. MtrC has significant sequence similarity to the paralogous decahaem cytochrome MtrF, which has been structurally solved through X-ray crystallography. This now allows for homology-based models of MtrC to be generated. The structure of these MtrC homology models contain ten bis-histidine-co-ordinated c-type haems arranged in a staggered cross through a four-domain structure. This model is consistent with current spectroscopic data and shows that the areas around haem 5 and haem 10, at the termini of an octahaem chain, are likely to havemore » functions similar to those of the corresponding haems in MtrF. The electrostatic surfaces around haem 7, close to the β-barrels, are different in MtrF and MtrC, indicating that these haems may have different potentials and interact with substrates differently.« less

Structure of the Escherichia coli Phosphonate Binding Protein PhnD and Rationally Optimized Phosphonate Biosensors

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

Alicea, Ismael; Marvin, Jonathan S.; Miklos, Aleksandr E.

2012-09-17

The phnD gene of Escherichia coli encodes the periplasmic binding protein of the phosphonate (Pn) uptake and utilization pathway. We have crystallized and determined structures of E. coli PhnD (EcPhnD) in the absence of ligand and in complex with the environmentally abundant 2-aminoethylphosphonate (2AEP). Similar to other bacterial periplasmic binding proteins, 2AEP binds near the center of mass of EcPhnD in a cleft formed between two lobes. Comparison of the open, unliganded structure with the closed 2AEP-bound structure shows that the two lobes pivot around a hinge by {approx}70{sup o} between the two states. Extensive hydrogen bonding and electrostatic interactionsmore » stabilize 2AEP, which binds to EcPhnD with low nanomolar affinity. These structures provide insight into Pn uptake by bacteria and facilitated the rational design of high signal-to-noise Pn biosensors based on both coupled small-molecule dyes and autocatalytic fluorescent proteins.« less

Exotic differentiable structures and general relativity

NASA Astrophysics Data System (ADS)

Brans, Carl H.; Randall, Duane

1993-02-01

We review recent developments in differential topology with special concern for their possible significance to physical theories, especially general relativity. In particular we are concerned here with the discovery of the existence of non-standard (“fake” or “exotic”) differentiable structures on topologically simple manifolds such asS 7, ℝ4 andS 3 X ℝ1. Because of the technical difficulties involved in the smooth case, we begin with an easily understood toy example looking at the role which the choice of complex structures plays in the formulation of two-dimensional vacuum electrostatics. We then briefly review the mathematical formalisms involved with differentiable structures on topological manifolds, diffeomorphisms and their significance for physics. We summarize the important work of Milnor, Freedman, Donaldson, and others in developing exotic differentiable structures on well known topological manifolds. Finally, we discuss some of the geometric implications of these results and propose some conjectures on possible physical implications of these new manifolds which have never before been considered as physical models.

How electrostatic networks modulate specificity and stability of collagen.

PubMed

Zheng, Hongning; Lu, Cheng; Lan, Jun; Fan, Shilong; Nanda, Vikas; Xu, Fei

2018-06-12

One-quarter of the 28 types of natural collagen exist as heterotrimers. The oligomerization state of collagen affects the structure and mechanics of the extracellular matrix, providing essential cues to modulate biological and pathological processes. A lack of high-resolution structural information limits our mechanistic understanding of collagen heterospecific self-assembly. Here, the 1.77-Å resolution structure of a synthetic heterotrimer demonstrates the balance of intermolecular electrostatics and hydrogen bonding that affects collagen stability and heterospecificity of assembly. Atomistic simulations and mutagenesis based on the solved structure are used to explore the contributions of specific interactions to energetics. A predictive model of collagen stability and specificity is developed for engineering novel collagen structures.

Metal Ion Binding at the Catalytic Site Induces Widely Distributed Changes in a Sequence Specific Protein–DNA Complex

PubMed Central

2016-01-01

Metal ion cofactors can alter the energetics and specificity of sequence specific protein–DNA interactions, but it is unknown if the underlying effects on structure and dynamics are local or dispersed throughout the protein–DNA complex. This work uses EcoRV endonuclease as a model, and catalytically inactive lanthanide ions, which replace the Mg2+ cofactor. Nuclear magnetic resonance (NMR) titrations indicate that four Lu3+ or two La3+ cations bind, and two new crystal structures confirm that Lu3+ binding is confined to the active sites. NMR spectra show that the metal-free EcoRV complex with cognate (GATATC) DNA is structurally distinct from the nonspecific complex, and that metal ion binding sites are not assembled in the nonspecific complex. NMR chemical shift perturbations were determined for 1H–15N amide resonances, for 1H–13C Ile-δ-CH3 resonances, and for stereospecifically assigned Leu-δ-CH3 and Val-γ-CH3 resonances. Many chemical shifts throughout the cognate complex are unperturbed, so metal binding does not induce major conformational changes. However, some large perturbations of amide and side chain methyl resonances occur as far as 34 Å from the metal ions. Concerted changes in specific residues imply that local effects of metal binding are propagated via a β-sheet and an α-helix. Both amide and methyl resonance perturbations indicate changes in the interface between subunits of the EcoRV homodimer. Bound metal ions also affect amide hydrogen exchange rates for distant residues, including a distant subdomain that contacts DNA phosphates and promotes DNA bending, showing that metal ions in the active sites, which relieve electrostatic repulsion between protein and DNA, cause changes in slow dynamics throughout the complex. PMID:27786446

Do surfaces of positive electrostatic potential on different halogen derivatives in molecules attract? like attracting like!

PubMed

Varadwaj, Arpita; Varadwaj, Pradeep R; Yamashita, Koichi

2018-03-15

Coulomb's law states that like charges repel, and unlike charges attract. However, it has recently been theoretically revealed that two similarly charged conducting spheres will almost always attract each other when both are in close proximity. Using multiscale first principles calculations, we illustrate practical examples of several intermolecular complexes that are formed by the consequences of attraction between positive atomic sites of similar or dissimilar electrostatic surface potential on interacting molecules. The results of the quantum theory of atoms in molecules and symmetry adapted perturbation theory support the attraction between the positive sites, characterizing the F•••X (X = F, Cl, Br) intermolecular interactions in a series of 20 binary complexes as closed-shell type, although the molecular electrostatic surface potential approach does not (a failure!). Dispersion that has an r -6 dependence, where r is the equilibrium distance of separation, is found to be the sole driving force pushing the two positive sites to attract. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Intermolecular interaction in nucleobases and dimethyl sulfoxide/water molecules: A DFT, NBO, AIM and NCI analysis.

PubMed

Venkataramanan, Natarajan Sathiyamoorthy; Suvitha, Ambigapathy; Kawazoe, Yoshiyuki

2017-11-01

This study aims to cast light on the physico-chemical nature and energetics of interactions between the nucleobases and water/DMSO molecules which occurs through the non-conventional CH⋯O/N-H bonds using a comprehensive quantum-chemical approach. The computed interaction energies do not show any appreciable change for all the nucleobase-solvent complexes, conforming the experimental findings on the hydration enthalpies. Compared to water, DMSO form complexes with high interaction energies. The quantitative molecular electrostatic potentials display a charge transfer during the complexation. NBO analysis shows the nucleobase-DMSO complexes, have higher stabilization energy values than the nucleobase-water complexes. AIM analysis illustrates that the in the nucleobase-DMSO complexes, SO⋯H-N type interaction have strongest hydrogen bond strength with high E HB values. Furthermore, the Laplacian of electron density and total electron density were negative indicating the partial covalent nature of bonding in these systems, while the other bonds are classified as noncovalent interactions. EDA analysis indicates, the electrostatic interaction is more pronounced in the case of nucleobase-water complexes, while the dispersion contribution is more dominant in nucleobase-DMSO complexes. NCI-RDG analysis proves the existence of strong hydrogen bonding in nucleobase-DMSO complex, which supports the AIM results. Copyright © 2017 Elsevier Inc. All rights reserved.

Inter-subunit electrostatic interactions in ferritin molecule: comparison with inter-molecular interactions in crystals

NASA Astrophysics Data System (ADS)

Takahashi, Takuya; Hogyoku, Michiru; Nagayama, Kuniaki

1996-10-01

We evaluated the contribution of electrostatic interactions to the stability of macromolecular assembly in a horse L ferritin molecule composed of 24 subunits and the three-dimensional crystal of the ferritin molecules with numerical calculation of Poisson-Boltzmann equation based on dielectric model. The calculation showed that the electrostatic energy both favors the assembly of the 24 subunits and the crystalline assembly of the ferritin molecules (i.e., 24-mers). Short-range interactions less than 5 Å such as salt bridges and hydrogen bonds were important for both the subunit assembly and the crystalline assembly. To elucidate the strong stabilization by electrostatic interactions in both the ferritin 24-mer and its crystal, we analyzed the contribution of individual atoms. It revealed that the stabilization was arising from buried salt bridges or hydrogen bonds, which yielded more than 5 kcal/mol in some interactions. These large electrostatic stabilization and also the unexpected small ionic strength dependence was different from those of bovine pancreatic trypsin inhibitor (BPTI) orthorhombic and pig-insulin cubic crystals previously calculated. We also evaluated changes of the accessible surface area (ASA) and hydration free energy in accordance with the process of the subunit assembly. The change of hydration free energy, which was very large (i.e. ˜ + 100 kcal/mol/subunit) and unfavorable for the assembly, was proportional to the electrostatic hydration energy (i.e. Born energy change in hydration process). Hydrophobic groups were likely to appear more frequently than hydrophilic groups at the subunit interfaces. These results suggest that the molecular structure of the ferritin 24-mer and the crystal structure of the 24-mers were both stabilized by local electrostatic interactions, in particular. We view protein crystals as an extension of the protein oligomer to an infinite number of subunits association.

Designing pH induced fold switch in proteins

NASA Astrophysics Data System (ADS)

Baruah, Anupaul; Biswas, Parbati

2015-05-01

This work investigates the computational design of a pH induced protein fold switch based on a self-consistent mean-field approach by identifying the ensemble averaged characteristics of sequences that encode a fold switch. The primary challenge to balance the alternative sets of interactions present in both target structures is overcome by simultaneously optimizing two foldability criteria corresponding to two target structures. The change in pH is modeled by altering the residual charge on the amino acids. The energy landscape of the fold switch protein is found to be double funneled. The fold switch sequences stabilize the interactions of the sites with similar relative surface accessibility in both target structures. Fold switch sequences have low sequence complexity and hence lower sequence entropy. The pH induced fold switch is mediated by attractive electrostatic interactions rather than hydrophobic-hydrophobic contacts. This study may provide valuable insights to the design of fold switch proteins.

Method for fabricating five-level microelectromechanical structures and microelectromechanical transmission formed

DOEpatents

Rodgers, M. Steven; Sniegowski, Jeffry J.; Miller, Samuel L.; McWhorter, Paul J.

2000-01-01

A process for forming complex microelectromechanical (MEM) devices having five layers or levels of polysilicon, including four structural polysilicon layers wherein mechanical elements can be formed, and an underlying polysilicon layer forming a voltage reference plane. A particular type of MEM device that can be formed with the five-level polysilicon process is a MEM transmission for controlling or interlocking mechanical power transfer between an electrostatic motor and a self-assembling structure (e.g. a hinged pop-up mirror for use with an incident laser beam). The MEM transmission is based on an incomplete gear train and a bridging set of gears that can be moved into place to complete the gear train to enable power transfer. The MEM transmission has particular applications as a safety component for surety, and for this purpose can incorporate a pin-in-maze discriminator responsive to a coded input signal.

Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel

NASA Astrophysics Data System (ADS)

Long, Stephen B.; Campbell, Ernest B.; MacKinnon, Roderick

2005-08-01

Voltage-dependent potassium ion (K+) channels (Kv channels) conduct K+ ions across the cell membrane in response to changes in the membrane voltage, thereby regulating neuronal excitability by modulating the shape and frequency of action potentials. Here we report the crystal structure, at a resolution of 2.9 angstroms, of a mammalian Kv channel, Kv1.2, which is a member of the Shaker K+ channel family. This structure is in complex with an oxido-reductase β subunit of the kind that can regulate mammalian Kv channels in their native cell environment. The activation gate of the pore is open. Large side portals communicate between the pore and the cytoplasm. Electrostatic properties of the side portals and positions of the T1 domain and β subunit are consistent with electrophysiological studies of inactivation gating and with the possibility of K+ channel regulation by the β subunit.

A novel multi-level IC-compatible surface microfabrication technology for MEMS with independently controlled lateral and vertical submicron transduction gaps

NASA Astrophysics Data System (ADS)

Cicek, Paul-Vahe; Elsayed, Mohannad; Nabki, Frederic; El-Gamal, Mourad

2017-11-01

An above-IC compatible multi-level MEMS surface microfabrication technology based on a silicon carbide structural layer is presented. The fabrication process flow provides optimal electrostatic transduction by allowing the creation of independently controlled submicron vertical and lateral gaps without the need for high resolution lithography. Adopting silicon carbide as the structural material, the technology ensures material, chemical and thermal compatibility with modern semiconductor nodes, reporting the lowest peak processing temperature (i.e. 200 °C) of all comparable works. This makes this process ideally suited for integrating capacitive-based MEMS directly above standard CMOS substrates. Process flow design and optimization are presented in the context of bulk-mode disk resonators, devices that are shown to exhibit improved performance with respect to previous generation flexural beam resonators, and that represent relatively complex MEMS structures. The impact of impending improvements to the fabrication technology is discussed.

Recent progress in biopolymer nanoparticle and microparticle formation by heat-treating electrostatic protein-polysaccharide complexes.

PubMed

Jones, Owen G; McClements, David Julian

2011-09-14

Functional biopolymer nanoparticles or microparticles can be formed by heat treatment of globular protein-ionic polysaccharide electrostatic complexes under appropriate solution conditions. These biopolymer particles can be used as encapsulation and delivery systems, fat mimetics, lightening agents, or texture modifiers. This review highlights recent progress in the design and fabrication of biopolymer particles based on heating globular protein-ionic polysaccharide complexes above the thermal denaturation temperature of the proteins. The influence of biopolymer type, protein-polysaccharide ratio, pH, ionic strength, and thermal history on the characteristics of the biopolymer particles formed is reviewed. Our current understanding of the underlying physicochemical mechanisms of particle formation and properties is given. The information provided in this review should facilitate the rational design of biopolymer particles with specific physicochemical and functional attributes, as well as stimulate further research in identifying the physicochemical origin of particle formation. Copyright © 2010 Elsevier B.V. All rights reserved.

Exosites in the substrate specificity of blood coagulation reactions.

PubMed

Bock, P E; Panizzi, P; Verhamme, I M A

2007-07-01

The specificity of blood coagulation proteinases for substrate, inhibitor, and effector recognition is mediated by exosites on the surfaces of the catalytic domains, physically separated from the catalytic site. Some thrombin ligands bind specifically to either exosite I or II, while others engage both exosites. The involvement of different, overlapping constellations of exosite residues enables binding of structurally diverse ligands. The flexibility of the thrombin structure is central to the mechanism of complex formation and the specificity of exosite interactions. Encounter complex formation is driven by electrostatic ligand-exosite interactions, followed by conformational rearrangement to a stable complex. Exosites on some zymogens are in low affinity proexosite states and are expressed concomitant with catalytic site activation. The requirement for exosite expression controls the specificity of assembly of catalytic complexes on the coagulation pathway, such as the membrane-bound factor Xa*factor Va (prothrombinase) complex, and prevents premature assembly. Substrate recognition by prothrombinase involves a two-step mechanism with initial docking of prothrombin to exosites, followed by a conformational change to engage the FXa catalytic site. Prothrombin and its activation intermediates bind prothrombinase in two alternative conformations determined by the zymogen to proteinase transition that are hypothesized to involve prothrombin (pro)exosite I interactions with FVa, which underpin the sequential activation pathway. The role of exosites as the major source of substrate specificity has stimulated development of exosite-targeted anticoagulants for treatment of thrombosis.

Effect of fish gelatin-gum arabic interactions on structural and functional properties of concentrated emulsions.

PubMed

Anvari, Mohammad; Joyner Melito, Helen S

2017-12-01

Concentrated emulsions containing both proteins and polysaccharides are the basis for many commercial products; however, the effects of protein-polysaccharide interactions on the functional properties of these complex systems are often poorly understood from a fundamental standpoint. Hence, the objective of this study was to determine the effects of fish gelatin (FG)-gum arabic (GA) complexation at different aqueous phase pH (3.6, 5.0, and 9.0) on concentrated emulsion structure-function relationships. Concentrated emulsions were prepared using FG-GA mixtures and characterized by rheometry and confocal scanning laser microscopy (CSLM). CSLM images showed that all samples were O/W emulsions; emulsions with lower pH showed smaller oil droplets, greater homogeneity in size distribution, and higher stability. This was attributed to an increased number of FG-GA complexes in the emulsification. Electrostatic attractive interactions and charge neutralization created biopolymer associations with increased emulsification capacity. Samples with FG-GA mixtures at lower pH showed higher elastic moduli under small deformation and exhibited greater deviation between apparent and complex viscosities under the Cox-Merz rule, indicating increased gel network extension and greater intermolecular connectivity between adsorbed layers of adjacent oil droplets. These results can be used to incorporate protein-polysaccharide complexes as a suitable emulsifier in materials comprising concentrated emulsions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and characterisation of semi-crystalline composite granules: The effect of particle chemistry and the electrostatic charging

NASA Astrophysics Data System (ADS)

Haque, Syed N.; Hussain, Tariq; Chowdhry, Babur Z.; Douroumis, Dennis; Scoutaris, Nikolaos; Nokhodchi, Ali; Maniruzzaman, Mohammed

2017-12-01

This study investigated the surface of semi-crystalline composite granules produced via a novel mechano-chemical process and assessed the effect of electrostatic charging. Ibuprofen (IBU), a model drug with low solubility and known associated processing challenges was loaded in composite granules to improve its processibility and dissolution rates. Synthetic amorphous mesoporous magnesium alumina metasilicate (MAS) was co-processed with hydrophilic HPMC polymer in the presence of polyethylene glycol 2000 (PEG) and deionised water. The solid state analyses conducted by scanning electron microscopy (SEM), X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) revealed the existence of semi-crystalline IBU in the complex composite structures. Dynamic vapour sorption (DVS) study showed the water sorption and desorption profiles of the manufactured composite granules as well as the effect of water on the solid-state stability of IBU in various formulations. Advanced surface analysis conducted via energy dispersive X-ray (EDS) revealed homogenous distribution of the drug/excipients on the surface of the granules while atomic force microscopy (AFM) complemented the findings. The electrostatic charge analysis showed variable charge property which is affected by the size of the particles/granules. As expected, the in vitro dissolution study showed about 5 fold increase in the release rates of IBU compared to that of the bulk drug. The mechanochemical processing has been demonstrated as an efficient technique to develop semi-crystalline composite granules with enhanced dissolution rates of water insoluble drugs.

Mechanochemical Preparation of Stable Sub-100 nm γ-Cyclodextrin:Buckminsterfullerene (C60) Nanoparticles by Electrostatic or Steric Stabilization.

PubMed

Van Guyse, Joachim F R; de la Rosa, Victor R; Hoogenboom, Richard

2018-02-21

Buckminster fullerene (C 60 )'s main hurdle to enter the field of biomedicine is its low bioavailability, which results from its extremely low water solubility. A well-known approach to increase the water solubility of C 60 is by complexation with γ-cyclodextrins. However, the formed complexes are not stable in time as they rapidly aggregate and eventually precipitate due to attractive intermolecular forces, a common problem in inclusion complexes of cyclodextrins. In this study we attempt to overcome the attractive intermolecular forces between the complexes by designing custom γ-cyclodextrin (γCD)-based supramolecular hosts for C 60 that inhibit the aggregation found in native γCD-C 60 complexes. The approach entails the introduction of either repulsive electrostatic forces or increased steric hindrance to prevent aggregation, thus enhancing the biomedical application potential of C 60 . These modifications have led to new sub-100 nm nanostructures that show long-term stability in solution. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solution NMR structure of CsgE: Structural insights into a chaperone and regulator protein important for functional amyloid formation.

PubMed

Shu, Qin; Krezel, Andrzej M; Cusumano, Zachary T; Pinkner, Jerome S; Klein, Roger; Hultgren, Scott J; Frieden, Carl

2016-06-28

Curli, consisting primarily of major structural subunit CsgA, are functional amyloids produced on the surface of Escherichia coli, as well as many other enteric bacteria, and are involved in cell colonization and biofilm formation. CsgE is a periplasmic accessory protein that plays a crucial role in curli biogenesis. CsgE binds to both CsgA and the nonameric pore protein CsgG. The CsgG-CsgE complex is the curli secretion channel and is essential for the formation of the curli fibril in vivo. To better understand the role of CsgE in curli formation, we have determined the solution NMR structure of a double mutant of CsgE (W48A/F79A) that appears to be similar to the wild-type (WT) protein in overall structure and function but does not form mixed oligomers at NMR concentrations similar to the WT. The well-converged structure of this mutant has a core scaffold composed of a layer of two α-helices and a layer of three-stranded antiparallel β-sheet with flexible N and C termini. The structure of CsgE fits well into the cryoelectron microscopy density map of the CsgG-CsgE complex. We highlight a striking feature of the electrostatic potential surface in CsgE structure and present an assembly model of the CsgG-CsgE complex. We suggest a structural mechanism of the interaction between CsgE and CsgA. Understanding curli formation can provide the information necessary to develop treatments and therapeutic agents for biofilm-related infections and may benefit the prevention and treatment of amyloid diseases. CsgE could establish a paradigm for the regulation of amyloidogenesis because of its unique role in curli formation.

Quenching interaction of BSA with DTAB is dynamic in nature: A spectroscopic insight

NASA Astrophysics Data System (ADS)

Das, Nirmal Kumar; Pawar, Lavanya; Kumar, Naveen; Mukherjee, Saptarshi

2015-08-01

The role of electrostatic interactions between the protein, Bovine Serum Albumin (BSA) and the cationic surfactant, dodecyltrimethylammonium bromide (DTAB) has been substantiated using spectroscopic approaches. The primary mechanism of fluorescence quenching of the tryptophan of BSA is most probably dynamic in nature as the complex formation resulting in a protein-surfactant assembly is not very spontaneous. The weak interaction buries the tryptophan amino acid residue inside the protein scaffolds which have been quantitatively proved by our acrylamide quenching studies. The loss in the secondary structure of the protein as a result of interaction with DTAB has been elucidated by CD spectroscopy.

DNA interactions of non-chelating tinidazole-based coordination compounds and their structural, redox and cytotoxic properties.

PubMed

Castro-Ramírez, Rodrigo; Ortiz-Pastrana, Naytzé; Caballero, Ana B; Zimmerman, Matthew T; Stadelman, Bradley S; Gaertner, Andrea A E; Brumaghim, Julia L; Korrodi-Gregório, Luís; Pérez-Tomás, Ricardo; Gamez, Patrick; Barba-Behrens, Norah

2018-05-23

Novel tinidazole (tnz) coordination compounds of different geometries were synthesised, whose respective solid-state packing appears to be driven by inter- and intramolecular lone pairπ interactions. The copper(ii) compounds exhibit interesting redox properties originating from both the tnz and the metal ions. These complexes interact with DNA through two distinct ways, namely via electrostatic interactions or/and groove binding, and they can mediate the generation of ROS that damage the biomolecule. Cytotoxic studies revealed an interesting activity of the dinuclear compound [Cu(tnz)2(μ-Cl)Cl]2 7, which is further more efficient towards cancer cells, compared with normal cells.

Electrostatic antenna space environment interaction study

NASA Technical Reports Server (NTRS)

Katz, I.

1981-01-01

The interactions of the electrostatic antenna with the space environment in both low Earth orbit and geosynchronous orbit are investigated. It is concluded that the electrostatically controlled membrane mirror is a viable concept for space applications. However, great care must be taken to enclose the high voltage electrodes in a Faraday cage structure to separate the high voltage region from the ambient plasma. For this reason, metallized cloth is not acceptable as a membrane material. Conventional spacecraft charging at geosynchronous orbit should not be a problem provided ancillary structures (such as booms) are given nonnegligible conductivity and adequate grounding. Power loss due to plasma electrons entering the high field region is a potentially serious problem. In low earth orbit any opening whatever in the Faraday cage is likely to produce an unacceptable power drain.

Influence of Structure, Charge, and Concentration on the Pectin-Calcium-Surfactant Complexes.

PubMed

Joshi, Nidhi; Rawat, Kamla; Bohidar, H B

2016-05-12

Polymer-surfactant complex formation of pectin with different types of surfactants, cationic (cetyltrimethylammonium bromide, CTAB and dodecyl trimethylammonium bromide, DTAB), anionic (sodium dodecyl sulfate, SDS), and neutral (Triton X-100, TX-100), was investigated at room temperature in the presence and absence of cross-linker calcium chloride using light scattering, zeta potential, rheology, and UV-vis spectroscopic measurements where the surfactant concentration was maintained below their critical micellar concentration (CMC). Results indicated that the interaction of cationic surfactant with pectin in the presence and absence of calcium chloride was much stronger compared to anionic and neutral surfactants. The neutral surfactant showed identifiable interaction despite the absence of any charged headgroup, while anionic surfactant showed feeble or very weak interaction with the polymer. The pectin-CTAB or DTAB complex formation was attributed to associative electrostatic and hydrophobic interactions. On comparison between the cationic surfactants, it was found that CTAB interacts strongly with pectin because of its long hydrocarbon chain. The morphology of complexes formed exhibited random coil structures while at higher concentration of surfactant, rod-like or extended random coil structures were noticed. Thus, functional characteristics of the complex could be tuned by varying the type of surfactant (charge and structure) and its concentration. The differential network rigidity (pectin-CTAB versus pectin-DTAB gels) obtained from rheology measurements showed that addition of a very small amount of surfactant (concentration ≪ CMC) was required for enhancing network strength, while the presence of a large amount of surfactant resulted in the formation of fragile gels. No gel formation occurred when the surfactant concentration was close to their CMC values. Considering the importance of pectin in food and pharmaceutical industry, this study is relevant.

Silicon supported lipid-DNA thin film structures at varying temperature studied by energy dispersive X-ray diffraction and neutron reflectivity.

PubMed

Domenici, F; Castellano, C; Dell'Unto, F; Albinati, A; Congiu, A

2011-11-01

Non-viral gene transfection by means of lipid-based nanosystems, such as solid supported lipid assemblies, is often limited due to their lack of stability and the consequent loss of efficiency. Therefore not only a detailed thermo-lyotropic study of these DNA-lipid complexes is necessary to understand their interaction mechanisms, but it can also be considered as a first step in conceiving and developing new transfection biosystems. The aim of our study is a structural characterization of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC)-dimethyl-dioctadecyl-ammonium bromide (DDAB)-DNA complex at varying temperature using the energy dispersive X-ray diffraction (EDXD) and neutron reflectivity (NR) techniques. We have shown the formation of a novel thermo-lyotropic structure of DOPC/DDAB thin film self-organized in multi-lamellar planes on (100)-oriented silicon support by spin coating, thus enlightening its ability to include DNA strands. Our NR measurements indicate that the DOPC/DDAB/DNA complex forms temperature-dependent structures. At 65°C and relative humidity of 100% DNA fragments are buried between single lamellar leaflets constituting the hydrocarbon core of the lipid bilayers. This finding supports the consistency of the hydrophobic interaction model, which implies that the coupling between lipid tails and hypo-hydrated DNA single strands could be the driving force of DNA-lipid complexation. Upon cooling to 25°C, EDXD analysis points out that full-hydrated DOPC-DDAB-DNA can switch in a different metastable complex supposed to be driven by lipid heads-DNA electrostatic interaction. Thermotropic response analysis also clarifies that DOPC has a pivotal role in promoting the formation of our observed thermophylic silicon supported lipids-DNA assembly. Copyright © 2011 Elsevier B.V. All rights reserved.

Computer simulations of the interaction of human immunodeficiency virus (HIV) aspartic protease with spherical gold nanoparticles: implications in acquired immunodeficiency syndrome (AIDS)

NASA Astrophysics Data System (ADS)

Whiteley, Chris G.; Lee, Duu-Jong

2016-09-01

The interaction of gold nanoparticles (AuNP) with human immune-deficiency virus aspartic protease (HIVPR) is modelled using a regime of molecular dynamics simulations. The simulations of the ‘docking’, first as a rigid-body complex, and eventually through flexible-fit analysis, creates 36 different complexes from four initial orientations of the nanoparticle strategically positioned around the surface of the enzyme. The structural deviations of the enzymes from the initial x-ray crystal structure during each docking simulation are assessed by comparative analysis of secondary structural elements, root mean square deviations, B-factors, interactive bonding energies, dihedral angles, radius of gyration (R g), circular dichroism (CD), volume occupied by C α , electrostatic potentials, solvation energies and hydrophobicities. Normalisation of the data narrows the selection from the initial 36 to one ‘final’ probable structure. It is concluded that, after computer simulations on each of the 36 initial complexes incorporating the 12 different biophysical techniques, the top five complexes are the same no matter which technique is explored. The significance of the present work is an expansion of an earlier study on the molecular dynamic simulation for the interaction of HIVPR with silver nanoparticles. This work is supported by experimental evidence since the initial ‘orientation’ of the AgNP with the enzyme is the same as the ‘final’ AuNP-HIVPR complex generated in the present study. The findings will provide insight into the forces of the binding of the HIVPR to AuNP. It is anticipated that the protocol developed in this study will act as a standard process for the interaction of any nanoparticle with any biomedical target.

Computer simulations of the interaction of human immunodeficiency virus (HIV) aspartic protease with spherical gold nanoparticles: implications in acquired immunodeficiency syndrome (AIDS).

PubMed

Whiteley, Chris G; Lee, Duu-Jong

2016-09-09

The interaction of gold nanoparticles (AuNP) with human immune-deficiency virus aspartic protease (HIVPR) is modelled using a regime of molecular dynamics simulations. The simulations of the 'docking', first as a rigid-body complex, and eventually through flexible-fit analysis, creates 36 different complexes from four initial orientations of the nanoparticle strategically positioned around the surface of the enzyme. The structural deviations of the enzymes from the initial x-ray crystal structure during each docking simulation are assessed by comparative analysis of secondary structural elements, root mean square deviations, B-factors, interactive bonding energies, dihedral angles, radius of gyration (R g), circular dichroism (CD), volume occupied by C α , electrostatic potentials, solvation energies and hydrophobicities. Normalisation of the data narrows the selection from the initial 36 to one 'final' probable structure. It is concluded that, after computer simulations on each of the 36 initial complexes incorporating the 12 different biophysical techniques, the top five complexes are the same no matter which technique is explored. The significance of the present work is an expansion of an earlier study on the molecular dynamic simulation for the interaction of HIVPR with silver nanoparticles. This work is supported by experimental evidence since the initial 'orientation' of the AgNP with the enzyme is the same as the 'final' AuNP-HIVPR complex generated in the present study. The findings will provide insight into the forces of the binding of the HIVPR to AuNP. It is anticipated that the protocol developed in this study will act as a standard process for the interaction of any nanoparticle with any biomedical target.

A pH-responsive carboxylic β-1,3-glucan polysaccharide for complexation with polymeric guests.

PubMed

Lien, Le Thi Ngoc; Shiraki, Tomohiro; Dawn, Arnab; Tsuchiya, Youichi; Tokunaga, Daisuke; Tamaru, Shun-ichi; Enomoto, Naoya; Hojo, Junichi; Shinkai, Seiji

2011-06-07

The helix-forming nature of β-1,3-glucan polysaccharides is a characteristic that has potential for producing gene carriers, bio-nanomaterials and other chiral nanowires. Herein, carboxylic curdlan (CurCOOH) bearing the β-1,3-polyglucuronic acid structure was successfully prepared from β-1,3-glucan polysaccharide curdlan (Cur) by one-step oxidation using a 4-acetamido-TEMPO/NaClO/NaClO(2) system as the oxidant. The resulting high-molecular-weight CurCOOH was proved to bear the 6-COOH group in 100% purity. The optical rotatory dispersion (ORD) spectra indicated that the obtained CurCOOH behaves as a water-soluble single-strand in various pH aqueous media. This advantage has allowed us to use CurCOOH as a polymeric host to form various macromolecular complexes. For example, complexation of CurCOOH with single-walled carbon nanotubes (SWNTs) resulted in a water-soluble one-dimensional architecture, which formed a dispersion in aqueous solution that was stable for several months, and much more stable than SWNTs complexes of the similar negatively-charged polyacrylic acid (PAA) and polymethacrylic acid (PMAA). It was shown that in the complex, SWNTs are effectively wrapped by a small amount of CurCOOH, enabling them to avoid electrostatic repulsion. This pH-responsive CurCOOH formed a very stable complex with cationic water-soluble polythiophenes (PT-1), which was stabilized not only by the hydrophobic interaction but also by the electrostatic attraction between trimethylammonium cations in PT-1 and dissociated anionic COO(-) groups in CurCOOH. The included PT-1 became CD-active only in the neutral to basic pH region, and the positive Cotton effect suggested that the conjugated main chain is twisted in the right-handed direction. We also found that CurCOOH can interact with polycytidylic acid (poly(C)) only under high NaCl concentrations, the binding and release of which could be controlled by a change in the salt concentration. We believe, therefore, that CurCOOH bearing a dissociable COOH group can act as a new potential polymeric host to construct novel polymeric complexes applicable for gene carriers, biosensors, chiral polymer assemblies, etc.

An expanded genetic code for probing the role of electrostatics in enzyme catalysis by vibrational Stark spectroscopy.

PubMed

Völler, Jan-Stefan; Biava, Hernan; Hildebrandt, Peter; Budisa, Nediljko

2017-11-01

To find experimental validation for electrostatic interactions essential for catalytic reactions represents a challenge due to practical limitations in assessing electric fields within protein structures. This review examines the applications of non-canonical amino acids (ncAAs) as genetically encoded probes for studying the role of electrostatic interactions in enzyme catalysis. ncAAs constitute sensitive spectroscopic probes to detect local electric fields by exploiting the vibrational Stark effect (VSE) and thus have the potential to map the protein electrostatics. Mapping the electrostatics in proteins will improve our understanding of natural catalytic processes and, in beyond, will be helpful for biocatalyst engineering. This article is part of a Special Issue entitled "Biochemistry of Synthetic Biology - Recent Developments" Guest Editor: Dr. Ilka Heinemann and Dr. Patrick O'Donoghue. Copyright © 2017 Elsevier B.V. All rights reserved.

The Crystal Structure of Coxsackievirus A21 and Its Interaction with ICAM-1

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

Xiao, Chuan; Bator-Kelly, Carol M.; Rieder, Elizabeth

2010-11-30

CVA21 and polioviruses both belong to the Enterovirus genus in the family of Picornaviridae, whereas rhinoviruses form a distinct picornavirus genus. Nevertheless, CVA21 and the major group of human rhinoviruses recognize intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, whereas polioviruses use poliovirus receptor. The crystal structure of CVA21 has been determined to 3.2 {angstrom} resolution. Its structure has greater similarity to poliovirus structures than to other known picornavirus structures. Cryo-electron microscopy (cryo-EM) was used to determine an 8.0 {angstrom} resolution structure of CVA21 complexed with an ICAM-1 variant, ICAM-1{sup Kilifi}. The cryo-EM map was fitted with the crystal structuresmore » of ICAM-1 and CVA21. Significant differences in the structure of CVA21 with respect to the poliovirus structures account for the inability of ICAM-1 to bind polioviruses. The interface between CVA21 and ICAM-1 has shape and electrostatic complementarity with many residues being conserved among those CVAs that bind ICAM-1.« less

Electronic structure and reactivity of three-coordinate iron complexes.

PubMed

Holland, Patrick L

2008-08-01

[Reaction: see text]. The identity and oxidation state of the metal in a coordination compound are typically thought to be the most important determinants of its reactivity. However, the coordination number (the number of bonds to the metal) can be equally influential. This Account describes iron complexes with a coordination number of only three, which differ greatly from iron complexes with octahedral (six-coordinate) geometries with respect to their magnetism, electronic structure, preference for ligands, and reactivity. Three-coordinate complexes with a trigonal-planar geometry are accessible using bulky, anionic, bidentate ligands (beta-diketiminates) that steer a monodentate ligand into the plane of their two nitrogen donors. This strategy has led to a variety of three-coordinate iron complexes in which iron is in the +1, +2, and +3 oxidation states. Systematic studies on the electronic structures of these complexes have been useful in interpreting their properties. The iron ions are generally high spin, with singly occupied orbitals available for pi interactions with ligands. Trends in sigma-bonding show that iron(II) complexes favor electronegative ligands (O, N donors) over electropositive ligands (hydride). The combination of electrostatic sigma-bonding and the availability of pi-interactions stabilizes iron(II) fluoride and oxo complexes. The same factors destabilize iron(II) hydride complexes, which are reactive enough to add the hydrogen atom to unsaturated organic molecules and to take part in radical reactions. Iron(I) complexes use strong pi-backbonding to transfer charge from iron into coordinated alkynes and N 2, whereas iron(III) accepts charge from a pi-donating imido ligand. Though the imidoiron(III) complex is stabilized by pi-bonding in the trigonal-planar geometry, addition of pyridine as a fourth donor weakens the pi-bonding, which enables abstraction of H atoms from hydrocarbons. The unusual bonding and reactivity patterns of three-coordinate iron compounds may lead to new catalysts for oxidation and reduction reactions and may be used by nature in transient intermediates of nitrogenase enzymes.

Noncovalent fabrication and tunable fusion of block copolymer-giant polyoxometalate hybrid micelles.

PubMed

Zhang, Liying; Li, Haolong; Wu, Lixin

2014-09-21

The block copolymers (BCs), as structure-directing agents, co-assembling with nanoscale inorganic additives is an important route to fabricate nanostructured hybrid materials. In this work, we present a facile approach to fabricate hybrid micelles composed of BCs and polyoxometalates (POMs), in which the POM clusters are premodified with the groups that can specifically interact with a certain BC block. A representative POM (NH4)42[Mo(132)O(372)(CH(3)COO)(30)(H2O)72] (Mo(132)) is chosen as the example and encapsulated with cationic molecules containing carboxyphenyl groups through electrostatic interactions, and then the resulting hybrid complex can further co-assemble with poly(styrene-block-4-vinylpyridine) (PS-b-P4VP) through hydrogen bonding with the pyridine groups, which leads to the formation of hybrid micelles and the localization of Mo(132) in the micelle cores. The micelles exhibit a high stability despite time and dilution. Furthermore, the fusion of the micelles can be readily adjusted by varying the length of PS blocks, which is promising to be used in constructing polymer-POM hybrid materials with discrete or continuous hybrid domains. This work is based on the electrostatic premodification of POMs and thus its concept is generally suitable for the whole anionic POM system, which may create a large class of BC-POM nanocomposites with tunable structures.

NASA Tech Briefs, April 2005

NASA Technical Reports Server (NTRS)

2005-01-01

Gas-Tolerant Device Senses Electrical Conductivity of Liquid Nanoactuators Based on Electrostatic Forces on Dielectrics Replaceable Microfluidic Cartridges for a PCR Biosensor CdZnTe Image Detectors for Hard-X-Ray Telescopes High-Aperture-Efficiency Horn Antenna Full-Circle Resolver-to-Linear-Analog Converter Continuous, Full-Circle Arctangent Circuit Advanced Three-Dimensional Display System Automatic Focus Adjustment of a Microscope Topics covered include: FastScript3D - A Companion to Java 3D; Generating Mosaics of Astronomical Images; Simulating Descent and Landing of a Spacecraft; Simulating Vibrations in a Complex Loaded Structure; Rover Sequencing and Visualization Program; Software Template for Instruction in Mathematics; Support for User Interfaces for Distributed Systems; Nanostructured MnO2-Based Cathodes for Li-Ion/Polymer Cells; Multi-Layer Laminated Thin Films for Inflatable Structures; Two-Step Laser Ranging for Precise Tracking of a Spacecraft; Growing Aligned Carbon Nanotubes for Interconnections in ICs; Multilayer Composite Pressure Vessels; Texturing Blood-Glucose-Monitoring Optics Using Oxygen Beams; Fault-Tolerant Heat Exchanger; Atomic Clock Based on Opto-Electronic Oscillator; Microfocus/Polycapillary-Optic Crystallographic X-Ray Sys; Depth-Penetrating Luminescence Thermography of Thermal- Barrier Coatings; One-Dimensional Photonic Crystal Superprisms; Measuring Low-Order Aberrations in a Segmented Telescope; Mapping From an Instrumented Glove to a Robot Hand; Application of the Hilbert-Huang Transform to Financial Data; Optimizing Parameters for Deep-Space Optical Communication; and Low-Shear Microencapsulation and Electrostatic Coating.

Influence of structural and surface properties of whey-derived peptides on zinc-chelating capacity, and in vitro gastric stability and bioaccessibility of the zinc-peptide complexes.

PubMed

Udechukwu, M Chinonye; Downey, Brianna; Udenigwe, Chibuike C

2018-02-01

Gastrointestinal stability of zinc-peptide complexes is essential for zinc delivery. As peptide surface charge can influence their metal complex stability, we evaluated the zinc-chelating capacity and stability of zinc complexes of whey protein hydrolysates (WPH), produced with Everlase (WPH-Ever; ζ-potential, -39mV) and papain (WPH-Pap; ζ-potential, -7mV), during simulated digestion. WPH-Ever had lower amount of zinc-binding amino acids but showed higher zinc-chelating capacity than WPH-Pap. This is attributable to the highly anionic surface charge of WPH-Ever for electrostatic interaction with zinc. Release of zinc during peptic digestion was lower for WPH-Ever-zinc, and over 50% of zinc remained bound in both peptide complexes after peptic-pancreatic digestion. Fourier transform infrared spectroscopy suggests the involvement of carboxylate ion, and sidechain carbon-oxygen of aspartate/glutamate and serine/threonine in zinc-peptide complexation. The findings indicate that strong zinc chelation can promote gastric stability and impede intestinal release, for peptides intended for use as dietary zinc carriers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Theoretical Prediction of the Heats of Formation, Densities, and Relative Sensitivities for 3,7-diamino-2,4,6,8-tetranitro-1,5-diazanaphthalene (DATNP) and 3,7-diamino-2,4,6,8-tetranitro-1,5-diazanaphthalene 1,5-N-oxide (DATNPO)

DTIC Science & Technology

2016-02-01

Figures Fig. 1 Optimized structure of a) 1 and b) 2 ......................................................2 Fig. 2 Electrostatic potential map of 1...3 Electrostatic potential map of 2, without a) and with b) molecule overlay...previous report.7 For the estimation of the impact sensitivities, the electrostatic maps on the 0.001 isosurfaces were generated with the scalar range

Continuum electromechanical modeling of protein-membrane interactions

NASA Astrophysics Data System (ADS)

Zhou, Y. C.; Lu, Benzhuo; Gorfe, Alemayehu A.

2010-10-01

A continuum electromechanical model is proposed to describe the membrane curvature induced by electrostatic interactions in a solvated protein-membrane system. The model couples the macroscopic strain energy of membrane and the electrostatic solvation energy of the system, and equilibrium membrane deformation is obtained by minimizing the electroelastic energy functional with respect to the dielectric interface. The model is illustrated with the systems with increasing geometry complexity and captures the sensitivity of membrane curvature to the permanent and mobile charge distributions.

Oligomerisation status and evolutionary conservation of interfaces of protein structural domain superfamilies.

PubMed

Sukhwal, Anshul; Sowdhamini, Ramanathan

2013-07-01

Protein-protein interactions are important in carrying out many biological processes and functions. These interactions may be either permanent or of temporary nature. Several studies have employed tools like solvent accessibility and graph theory to identify these interactions, but still more studies need to be performed to quantify and validate them. Although we now have many databases available with predicted and experimental results on protein-protein interactions, we still do not have many databases which focus on providing structural details of the interacting complexes, their oligomerisation state and homologues. In this work, protein-protein interactions have been thoroughly investigated within the structural regime and quantified for their strength using calculated pseudoenergies. The PPCheck server, an in-house webserver, has been used for calculating the pseudoenergies like van der Waals, hydrogen bonds and electrostatic energy based on distances between atoms of amino acids from two interacting proteins. PPCheck can be visited at . Based on statistical data, as obtained by studying established protein-protein interacting complexes from earlier studies, we came to a conclusion that an average protein-protein interface consisted of about 51 to 150 amino acid residues and the generalized energy per residue ranged from -2 kJ mol(-1) to -6 kJ mol(-1). We found that some of the proteins have an exceptionally higher number of amino acids at the interface and it was purely because of their elaborate interface or extended topology i.e. some of their secondary structure regions or loops were either inter-mixing or running parallel to one another or they were taking part in domain swapping. Residue networks were prepared for all the amino acids of the interacting proteins involved in different types of interactions (like van der Waals, hydrogen-bonding, electrostatic or intramolecular interactions) and were analysed between the query domain-interacting partner pair and its remote homologue-interacting partner pair. We found that, in exceptional cases, homologous proteins belonging to the same superfamily, but with remote sequence similarity, can share similar interfaces.

Probing the modulated formation of gold nanoparticles-beta-lactoglobulin corona complexes and their applications.

PubMed

Yang, Jiang; Wang, Bo; You, Youngsang; Chang, Woo-Jin; Tang, Ke; Wang, Yi-Cheng; Zhang, Wenzhao; Ding, Feng; Gunasekaran, Sundaram

2017-11-23

Understanding the interactions between proteins and nanoparticles (NPs) along with the underlying structural and dynamic information is of utmost importance to exploit nanotechnology for biomedical applications. Upon adsorption onto a NP surface, proteins form a well-organized layer, termed the corona, that dictates the identity of the NP-protein complex and governs its biological pathways. Given its high biological relevance, in-depth molecular investigations and applications of NPs-protein corona complexes are still scarce, especially since different proteins form unique corona patterns, making identification of the biomolecular motifs at the interface critical. In this work, we provide molecular insights and structural characterizations of the bio-nano interface of a popular food-based protein, namely bovine beta-lactoglobulin (β-LG), with gold nanoparticles (AuNPs) and report on our investigations of the formation of corona complexes by combined molecular simulations and complementary experiments. Two major binding sites in β-LG were identified as being driven by citrate-mediated electrostatic interactions, while the associated binding kinetics and conformational changes in the secondary structures were also characterized. More importantly, the superior stability of the corona led us to further explore its biomedical applications, such as in the smartphone-based point-of-care biosensing of Escherichia coli (E. coli) and in the computed tomography (CT) of the gastrointestinal (GI) tract through oral administration to probe GI tolerance and functions. Considering their biocompatibility, edible nature, and efficient excretion through defecation, AuNPs-β-LG corona complexes have shown promising perspectives for future in vitro and in vivo clinical settings.

An anti-DNA antibody prefers damaged dsDNA over native.

PubMed

Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

2017-01-01

DNA-protein interactions, including DNA-antibody complexes, have both fundamental and practical significance. In particular, antibodies against double-stranded DNA play an important role in the pathogenesis of autoimmune diseases. Elucidation of structural mechanisms of an antigen recognition and interaction of anti-DNA antibodies provides a basis for understanding the role of DNA-containing immune complexes in human pathologies and for new treatments. Here we used Molecular Dynamic simulations of bimolecular complexes of a segment of dsDNA with a monoclonal anti-DNA antibody's Fab-fragment to obtain detailed structural and physical characteristics of the dynamic intermolecular interactions. Using a computationally modified crystal structure of a Fab-DNA complex (PDB: 3VW3), we studied in silico equilibrium Molecular Dynamics of the Fab-fragment associated with two homologous dsDNA fragments, containing or not containing dimerized thymine, a product of DNA photodamage. The Fab-fragment interactions with the thymine dimer-containing DNA was thermodynamically more stable than with the native DNA. The amino acid residues constituting a paratope and the complementary nucleotide epitopes for both Fab-DNA constructs were identified. Stacking and electrostatic interactions were shown to play the main role in the antibody-dsDNA contacts, while hydrogen bonds were less significant. The aggregate of data show that the chemically modified dsDNA (containing a covalent thymine dimer) has a higher affinity toward the antibody and forms a stronger immune complex. These findings provide a mechanistic insight into formation and properties of the pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus, associated with skin photosensibilization and DNA photodamage.

Coarse-grained simulations of polyelectrolyte complexes: MARTINI models for poly(styrene sulfonate) and poly(diallyldimethylammonium)

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

Vögele, Martin; Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt a. M.; Holm, Christian

2015-12-28

We present simulations of aqueous polyelectrolyte complexes with new MARTINI models for the charged polymers poly(styrene sulfonate) and poly(diallyldimethylammonium). Our coarse-grained polyelectrolyte models allow us to study large length and long time scales with regard to chemical details and thermodynamic properties. The results are compared to the outcomes of previous atomistic molecular dynamics simulations and verify that electrostatic properties are reproduced by our MARTINI coarse-grained approach with reasonable accuracy. Structural similarity between the atomistic and the coarse-grained results is indicated by a comparison between the pair radial distribution functions and the cumulative number of surrounding particles. Our coarse-grained models aremore » able to quantitatively reproduce previous findings like the correct charge compensation mechanism and a reduced dielectric constant of water. These results can be interpreted as the underlying reason for the stability of polyelectrolyte multilayers and complexes and validate the robustness of the proposed models.« less

The (FHCl)- molecular anion - Structural aspects, global surface, and vibrational eigenspectrum

NASA Technical Reports Server (NTRS)

Klepeis, Neil E.; East, Allan L. L.; Csaszar, Attila G.; Allen, Wesley D.; Lee, Timothy J.; Schwenke, David W.

1993-01-01

State of the art ab initio electronic structure methods have been used to investigate the (FHCl)- molecular anion. It is proposed that the geometric structure and binding energies of the complex are r(e)(H-F) = 0.963 +/- 0.003 A, R(e)(H-Cl) = 1.925 +/- 0.015 A, and D0(HF + Cl(-)) = 21.8 +/- 0.4 kcal/mol. A Morokuma decomposition of the ion-molecular bonding give the following electrostatic, polarization, exchange repulsion, dispersion, and charge-transfer plus higher-order mixing components of the vibrationless complexation energy: -27.3, -5.2, +18.3, -4.5, and -5.0 kcal/mol, respectively. A couples cluster single and doubles global surface is constructed from 208 and 228 energy points for linear and bent configurations, respectively, these being fit to rms errors of only 3.9 and 9.3/cm, respectively, below 8000/cm. Converged J = 0 and J = 1 variational eigenstates of the (FHCl)- surface to near the HF + Cl(-) dissociation threshold are determined. The fundamental vibrational frequencies are found to be nu1 = 247/cm, nu2 = 876/cm, and nu3 = 2884/cm. The complete vibrational eigenspectrum is analyzed.

A highly modular beamline electrostatic levitation facility, optimized for in situ high-energy x-ray scattering studies of equilibrium and supercooled liquids

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

Mauro, N.A.; Kelton, K.F.

2011-10-27

High-energy x-ray diffraction studies of metallic liquids provide valuable information about structural evolution on the atomic length scale, leading to insights into the origin of the nucleation barrier and the processes of supercooling and glass formation. The containerless processing of the beamline electrostatic levitation (BESL) facility allows coordinated thermophysical and structural studies of equilibrium and supercooled liquids to be made in a contamination-free, high-vacuum ({approx}10{sup -8} Torr) environment. To date, the incorporation of electrostatic levitation facilities into synchrotron beamlines has been difficult due to the large footprint of the apparatus and the difficulties associated with its transportation and implementation. Here,more » we describe a modular levitation facility that is optimized for diffraction studies of high-temperature liquids at high-energy synchrotron beamlines. The modular approach used in the apparatus design allows it to be easily transported and quickly setup. Unlike most previous electrostatic levitation facilities, BESL can be operated by a single user instead of a user team.« less

Multilayer out-of-plane overlap electrostatic energy harvesting structure actuated by blood pressure for powering intra-cardiac implants

NASA Astrophysics Data System (ADS)

Deterre, M.; Risquez, S.; Bouthaud, B.; Dal Molin, R.; Woytasik, M.; Lefeuvre, E.

2013-12-01

We present an innovative multilayer out-of-plane electrostatic energy harvesting device conceived in view of scavenging energy from regular blood pressure in the heart. This concept involves the use of a deformable packaging for the implant in order to transmit the blood pressure to the electrostatic transducer. As shown in previous work, this is possible by using thin metal micro-bellows structure, providing long term hermeticity and high flexibility. The design of the electrostatic device has overcome several challenges such as the very low frequency of the mechanical excitation (1 to 2 Hz) and the small available room in the medical implant. Analytical and numerical models have been used to maximize the capacitance variation, and hence to optimize the energy conversion. We have theoretically shown that a 25-layer transducer with 6-mm diameter and 1-mm thickness could harvest at least 20 mJ per heart beat in the left ventricle under a maximum voltage of 75 V. These results show that the proposed concept is promising and could power the next generation of leadless pacemakers.

Second-sphere coordination in anion binding: Synthesis, characterization and X-ray structures of bis(diethylenetriamine)cobalt(III) complexes containing benzoates

NASA Astrophysics Data System (ADS)

Bala, Ritu; Kaur, Amrinder; Kashyap, Monika; Janzen, Daron E.

2014-04-01

New complexes of composition s-fac-[Co(dien)2]Cl2(Bz)·H2O (1), s-fac-[Co(dien)2]Cl(p-CBz)2·4.5H2O (2) and mer-[Co(dien)2](p-NBz)3·3H2O (3) were obtained by reacting aqueous solutions of bis(diethylenetriamine)cobalt(III) chloride and sodium salts of benzoates ((Bz = benzoate, CBz = p-chlorobenzoate, NBz = p-nitrobenzoate)) in 1:3 molar ratio. These complexes were characterized by TG analysis and spectroscopic studies (IR, NMR and UV-vis). IR and NMR studies were used for the isomeric identification of [Co(dien)2]3+ in new complexes. This cation, contains ligand diethylenetriamine (dien) bearing H-bond donors, capable of forming hydrogen bonds and its binding properties with benzoates have been studied using standard UV-vis spectroscopic titrations in aqueous medium (log k for Bz = 2.11, p-CBz = 3.64 and p-NBz = 3.66). Single crystal X-ray study of complex 2 and 3 reveals that both the structures are dominantly stabilized by second-sphere coordination through H-bonding interactions of type-NH (dien)⋯O (benzoates) and H (water)⋯O (benzoates) in addition to the electrostatic forces of attractions. Further, the NH (dien)⋯Cl- (counter ion) and NH (dien)⋯O (water) types of interactions are also playing a dominant role to stabilize the crystal lattice in complex 2 and 3 respectively.

Molecular electrostatics for probing lone pair-π interactions.

PubMed

Mohan, Neetha; Suresh, Cherumuttathu H; Kumar, Anmol; Gadre, Shridhar R

2013-11-14

An electrostatics-based approach has been proposed for probing the weak interactions between lone pair containing molecules and π deficient molecular systems. For electron-rich molecules, the negative minima in molecular electrostatic potential (MESP) topography give the location of electron localization and the MESP value at the minimum (Vmin) quantifies the electron-rich character of that region. Interactive behavior of a lone pair bearing molecule with electron deficient π-systems, such as hexafluorobenzene, 1,3,5-trinitrobenzene, 2,4,6-trifluoro-1,3,5-triazine and 1,2,4,5-tetracyanobenzene explored within DFT brings out good correlation of the lone pair-π interaction energy (E(int)) with the Vmin value of the electron-rich system. Such interaction is found to be portrayed well with the Electrostatic Potential for Intermolecular Complexation (EPIC) model. On the basis of the precise location of MESP minimum, a prediction for the orientation of a lone pair bearing molecule with an electron deficient π-system is possible in the majority of the cases studied.

Implications of hydrogen/halogen-bond in the stabilization of confined water and anion-water clusters by a cationic receptor

NASA Astrophysics Data System (ADS)

Hoque, Md. Najbul; Das, Gopal

2016-03-01

Anion complexation of benzene capped flexible tripodal receptor and solid state stabilization of discrete hybrid anion-water or infinite water clusters by various supramolecular interactions are reported here. The crystal structure of the receptor in protonated states shows all the three arms projected in one direction. We structurally demonstrate discrete fluoride-water cluster [F2-H2O]2- and square shaped chloride-water cluster [Cl2-(H2O)2]2- inside the cationic channel of the receptor. Structural analysis also reveals that these clusters are stabilized inside the channel through active participation of N/C/Ow‧H⋯Ow, N/C/Ow‧H⋯X- (X- = F-, Cl- and I-) H-bonds and electrostatic interactions. Moreover, C-H⋯π and π⋯π types weak intermolecular interactions appear to play crucial role in supramolecular assembly of receptor. Additionally, on treatment with hydroiodic acid (HI) L resulted zwitterionic iodide complex. Crystal structure reveals the presence of S···I halogen bonded dimer, I2···I halogen bond, 1D infinite water chain and neutral iodine molecules. It is comprehensible that ligand basal structure (benzene capped and N-bridge head in two tripodal) play crucial roles in the formation of diverse halide-water cluster. All structures were well examined by different techniques such as NMR, IR, TGA, DSC, PXRD and XRD.

Structural and Functional Studies of H. seropedicae RecA Protein - Insights into the Polymerization of RecA Protein as Nucleoprotein Filament.

PubMed

Leite, Wellington C; Galvão, Carolina W; Saab, Sérgio C; Iulek, Jorge; Etto, Rafael M; Steffens, Maria B R; Chitteni-Pattu, Sindhu; Stanage, Tyler; Keck, James L; Cox, Michael M

2016-01-01

The bacterial RecA protein plays a role in the complex system of DNA damage repair. Here, we report the functional and structural characterization of the Herbaspirillum seropedicae RecA protein (HsRecA). HsRecA protein is more efficient at displacing SSB protein from ssDNA than Escherichia coli RecA protein. HsRecA also promotes DNA strand exchange more efficiently. The three dimensional structure of HsRecA-ADP/ATP complex has been solved to 1.7 Å resolution. HsRecA protein contains a small N-terminal domain, a central core ATPase domain and a large C-terminal domain, that are similar to homologous bacterial RecA proteins. Comparative structural analysis showed that the N-terminal polymerization motif of archaeal and eukaryotic RecA family proteins are also present in bacterial RecAs. Reconstruction of electrostatic potential from the hexameric structure of HsRecA-ADP/ATP revealed a high positive charge along the inner side, where ssDNA is bound inside the filament. The properties of this surface may explain the greater capacity of HsRecA protein to bind ssDNA, forming a contiguous nucleoprotein filament, displace SSB and promote DNA exchange relative to EcRecA. Our functional and structural analyses provide insight into the molecular mechanisms of polymerization of bacterial RecA as a helical nucleoprotein filament.

Impact of Electrostatics on Processing and Product Performance of Pharmaceutical Solids.

PubMed

Desai, Parind Mahendrakumar; Tan, Bernice Mei Jin; Liew, Celine Valeria; Chan, Lai Wah; Heng, Paul Wan Sia

2015-01-01

Manufacturing of pharmaceutical solids involves different unit operations and processing steps such as powder blending, fluidization, sieving, powder coating, pneumatic conveying and spray drying. During these operations, particles come in contact with other particles, different metallic, glass or polymer surfaces and can become electrically charged. Electrostatic charging often gives a negative connotation as it creates sticking, jamming, segregation or other issues during tablet manufacturing, capsule filling, film packaging and other pharmaceutical operations. A thorough and fundamental appreciation of the current knowledge of mechanisms and the potential outcomes is essential in order to minimize potential risks resulting from this phenomenon. The intent of this review is to discuss the electrostatic properties of pharmaceutical powders, equipment surfaces and devices affecting pharmaceutical processing and product performance. Furthermore, the underlying mechanisms responsible for the electrostatic charging are described and factors affecting electrostatic charging have been reviewed in detail. Feasibility of different methods used in the laboratory and pharmaceutical industry to measure charge propensity and decay has been summarized. Different computational and experimental methods studied have proven that the particle charging is a very complex phenomenon and control of particle charging is extremely important to achieve reliable manufacturing and reproducible product performance.

Improving the treatment of coarse-grain electrostatics: CVCEL.

PubMed

Ceres, N; Lavery, R

2015-12-28

We propose an analytic approach for calculating the electrostatic energy of proteins or protein complexes in aqueous solution. This method, termed CVCEL (Circular Variance Continuum ELectrostatics), is fitted to Poisson calculations and is able to reproduce the corresponding energies for different choices of solute dielectric constant. CVCEL thus treats both solute charge interactions and charge self-energies, and it can also deal with salt solutions. Electrostatic damping notably depends on the degree of solvent exposure of the charges, quantified here in terms of circular variance, a measure that reflects the vectorial distribution of the neighbors around a given center. CVCEL energies can be calculated rapidly and have simple analytical derivatives. This approach avoids the need for calculating effective atomic volumes or Born radii. After describing how the method was developed, we present test results for coarse-grain proteins of different shapes and sizes, using different internal dielectric constants and different salt concentrations and also compare the results with those from simple distance-dependent models. We also show that the CVCEL approach can be used successfully to calculate the changes in electrostatic energy associated with changes in protein conformation or with protein-protein binding.

Probing the electrostatics of active site microenvironments along the catalytic cycle for Escherichia coli dihydrofolate reductase.

PubMed

Liu, C Tony; Layfield, Joshua P; Stewart, Robert J; French, Jarrod B; Hanoian, Philip; Asbury, John B; Hammes-Schiffer, Sharon; Benkovic, Stephen J

2014-07-23

Electrostatic interactions play an important role in enzyme catalysis by guiding ligand binding and facilitating chemical reactions. These electrostatic interactions are modulated by conformational changes occurring over the catalytic cycle. Herein, the changes in active site electrostatic microenvironments are examined for all enzyme complexes along the catalytic cycle of Escherichia coli dihydrofolate reductase (ecDHFR) by incorporation of thiocyanate probes at two site-specific locations in the active site. The electrostatics and degree of hydration of the microenvironments surrounding the probes are investigated with spectroscopic techniques and mixed quantum mechanical/molecular mechanical (QM/MM) calculations. Changes in the electrostatic microenvironments along the catalytic environment lead to different nitrile (CN) vibrational stretching frequencies and (13)C NMR chemical shifts. These environmental changes arise from protein conformational rearrangements during catalysis. The QM/MM calculations reproduce the experimentally measured vibrational frequency shifts of the thiocyanate probes across the catalyzed hydride transfer step, which spans the closed and occluded conformations of the enzyme. Analysis of the molecular dynamics trajectories provides insight into the conformational changes occurring between these two states and the resulting changes in classical electrostatics and specific hydrogen-bonding interactions. The electric fields along the CN axes of the probes are decomposed into contributions from specific residues, ligands, and solvent molecules that make up the microenvironments around the probes. Moreover, calculation of the electric field along the hydride donor-acceptor axis, along with decomposition of this field into specific contributions, indicates that the cofactor and substrate, as well as the enzyme, impose a substantial electric field that facilitates hydride transfer. Overall, experimental and theoretical data provide evidence for significant electrostatic changes in the active site microenvironments due to conformational motion occurring over the catalytic cycle of ecDHFR.