Science.gov

Sample records for gas-phase protein structure

  1. Amphipols Outperform Dodecylmaltoside Micelles in Stabilizing Membrane Protein Structure in the Gas Phase

    PubMed Central

    2014-01-01

    Noncovalent mass spectrometry (MS) is emerging as an invaluable technique to probe the structure, interactions, and dynamics of membrane proteins (MPs). However, maintaining native-like MP conformations in the gas phase using detergent solubilized proteins is often challenging and may limit structural analysis. Amphipols, such as the well characterized A8-35, are alternative reagents able to maintain the solubility of MPs in detergent-free solution. In this work, the ability of A8-35 to retain the structural integrity of MPs for interrogation by electrospray ionization-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS) is compared systematically with the commonly used detergent dodecylmaltoside. MPs from the two major structural classes were selected for analysis, including two β-barrel outer MPs, PagP and OmpT (20.2 and 33.5 kDa, respectively), and two α-helical proteins, Mhp1 and GalP (54.6 and 51.7 kDa, respectively). Evaluation of the rotationally averaged collision cross sections of the observed ions revealed that the native structures of detergent solubilized MPs were not always retained in the gas phase, with both collapsed and unfolded species being detected. In contrast, ESI-IMS-MS analysis of the amphipol solubilized MPs studied resulted in charge state distributions consistent with less gas phase induced unfolding, and the presence of lowly charged ions which exhibit collision cross sections comparable with those calculated from high resolution structural data. The data demonstrate that A8-35 can be more effective than dodecylmaltoside at maintaining native MP structure and interactions in the gas phase, permitting noncovalent ESI-IMS-MS analysis of MPs from the two major structural classes, while gas phase dissociation from dodecylmaltoside micelles leads to significant gas phase unfolding, especially for the α-helical MPs studied. PMID:25495802

  2. Exploring Salt Bridge Structures of Gas-Phase Protein Ions using Multiple Stages of Electron Transfer and Collision Induced Dissociation

    NASA Astrophysics Data System (ADS)

    Zhang, Zhe; Browne, Shaynah J.; Vachet, Richard W.

    2014-04-01

    The gas-phase structures of protein ions have been studied by electron transfer dissociation (ETD) and collision-induced dissociation (CID) after electrospraying these proteins from native-like solutions into a quadrupole ion trap mass spectrometer. Because ETD can break covalent bonds while minimally disrupting noncovalent interactions, we have investigated the ability of this dissociation technique together with CID to probe the sites of electrostatic interactions in gas-phase protein ions. By comparing spectra from ETD with spectra from ETD followed by CID, we find that several proteins, including ubiquitin, CRABP I, azurin, and β-2-microglobulin, appear to maintain many of the salt bridge contacts known to exist in solution. To support this conclusion, we also performed calculations to consider all possible salt bridge patterns for each protein, and we find that the native salt bridge pattern explains the experimental ETD data better than nearly all other possible salt bridge patterns. Overall, our data suggest that ETD and ETD/CID of native protein ions can provide some insight into approximate location of salt bridges in the gas phase.

  3. The role of the detergent micelle in preserving the structure of membrane proteins in the gas phase.

    PubMed

    Reading, Eamonn; Liko, Idlir; Allison, Timothy M; Benesch, Justin L P; Laganowsky, Arthur; Robinson, Carol V

    2015-04-01

    Despite the growing importance of the mass spectrometry of membrane proteins, it is not known how their transfer from solution into vacuum affects their stability and structure. To address this we have carried out a systematic investigation of ten membrane proteins solubilized in different detergents and used mass spectrometry to gain physicochemical insight into the mechanism of their ionization and desolvation. We show that the chemical properties of the detergents mediate the charge state, both during ionization and detergent removal. Using ion mobility mass spectrometry, we monitor the conformations of membrane proteins and show how the surface charge density dictates the stability of folded states. We conclude that the gas-phase stability of membrane proteins is increased when a greater proportion of their surface is lipophilic and is consequently protected by the physical presence of the micelle.

  4. Collision cross sections of proteins and their complexes: a calibration framework and database for gas-phase structural biology.

    PubMed

    Bush, Matthew F; Hall, Zoe; Giles, Kevin; Hoyes, John; Robinson, Carol V; Ruotolo, Brandon T

    2010-11-15

    Collision cross sections in both helium and nitrogen gases were measured directly using a drift cell with RF ion confinement inserted within a quadrupole/ion mobility/time-of-flight hybrid mass spectrometer (Waters Synapt HDMS, Manchester, U.K.). Collision cross sections for a large set of denatured peptide, denatured protein, native-like protein, and native-like protein complex ions are reported here, forming a database of collision cross sections that spans over 2 orders of magnitude. The average effective density of the native-like ions is 0.6 g cm(-3), which is significantly lower than that for the solvent-excluded regions of proteins and suggests that these ions can retain significant memory of their solution-phase structures rather than collapse to globular structures. Because the measurements are acquired using an instrument that mimics the geometry of the commercial Synapt HDMS instrument, this database enables the determination of highly accurate collision cross sections from traveling-wave ion mobility data through the use of calibration standards with similar masses and mobilities. Errors in traveling-wave collision cross sections determined for native-like protein complexes calibrated using other native-like protein complexes are significantly less than those calibrated using denatured proteins. This database indicates that collision cross sections in both helium and nitrogen gases can be well-correlated for larger biomolecular ions, but non-correlated differences for smaller ions can be more significant. These results enable the generation of more accurate three-dimensional models of protein and other biomolecular complexes using gas-phase structural biology techniques.

  5. Relating gas phase to solution conformations: Lessons from disordered proteins

    PubMed Central

    Beveridge, Rebecca; Phillips, Ashley S.; Denbigh, Laetitia; Saleem, Hassan M.; MacPhee, Cait E.

    2015-01-01

    In recent years both mass spectrometry (MS) and ion mobility mass spectrometry (IM‐MS) have been developed as techniques with which to study proteins that lack a fixed tertiary structure but may contain regions that form secondary structure elements transiently, namely intrinsically disordered proteins (IDPs). IM‐MS is a suitable method for the study of IDPs which provides an insight to conformations that are present in solution, potentially enabling the analysis of lowly populated structural forms. Here, we describe the IM‐MS data of two IDPs; α‐Synuclein (α‐Syn) which is implicated in Parkinson's disease, and Apolipoprotein C‐II (ApoC‐II) which is involved in cardiovascular diseases. We report an apparent discrepancy in the way that ApoC‐II behaves in the gas phase. While most IDPs, including α‐Syn, present in many charge states and a wide range of rotationally averaged collision cross sections (CCSs), ApoC‐II presents in just four charge states and a very narrow range of CCSs, independent of solution conditions. Here, we compare MS and IM‐MS data of both proteins, and rationalise the differences between the proteins in terms of different ionisation processes which they may adhere to. PMID:25920945

  6. Relating gas phase to solution conformations: Lessons from disordered proteins.

    PubMed

    Beveridge, Rebecca; Phillips, Ashley S; Denbigh, Laetitia; Saleem, Hassan M; MacPhee, Cait E; Barran, Perdita E

    2015-08-01

    In recent years both mass spectrometry (MS) and ion mobility mass spectrometry (IM-MS) have been developed as techniques with which to study proteins that lack a fixed tertiary structure but may contain regions that form secondary structure elements transiently, namely intrinsically disordered proteins (IDPs). IM-MS is a suitable method for the study of IDPs which provides an insight to conformations that are present in solution, potentially enabling the analysis of lowly populated structural forms. Here, we describe the IM-MS data of two IDPs; α-Synuclein (α-Syn) which is implicated in Parkinson's disease, and Apolipoprotein C-II (ApoC-II) which is involved in cardiovascular diseases. We report an apparent discrepancy in the way that ApoC-II behaves in the gas phase. While most IDPs, including α-Syn, present in many charge states and a wide range of rotationally averaged collision cross sections (CCSs), ApoC-II presents in just four charge states and a very narrow range of CCSs, independent of solution conditions. Here, we compare MS and IM-MS data of both proteins, and rationalise the differences between the proteins in terms of different ionisation processes which they may adhere to. PMID:25920945

  7. The 'sticky business' of cleaning gas-phase membrane proteins: a detergent oriented perspective.

    PubMed

    Borysik, Antoni J; Robinson, Carol V

    2012-11-14

    In recent years the properties of gas-phase detergent clusters have come under close scrutiny due in part to their participation in the analysis of intact membrane protein complexes by mass spectrometry. The detergent molecules that cover the protein complex are removed in the gas-phase by thermally agitating the ions by collision-induced dissociation. This process however, is not readily controlled and can frequently result in the disruption of protein structure. Improved methods of releasing proteins from detergent clusters are clearly required. To facilitate this the structural properties of detergent clusters along with the mechanistic details of their dissociation need to be understood. Pivotal to understanding the properties of gas-phase detergent clusters is the technique of ion mobility mass spectrometry. This technique can be used to assign polydisperse detergent clusters and provide information about their geometries and packing densities. In this article we consider the shapes of detergent clusters and show that these clusters possess geometries that are inconsistent with those in solution. We analyse the distributions of clusters in detail using tandem mass spectrometry and suggest that the mean charge of clusters formed from certain detergents is governed by electrostatic repulsion. We discuss the dissociation of detergent clusters and propose that detergent evaporation it a key process in the protection of protein complexes during high energy collisions in the gas-phase.

  8. Uridine Nucleoside Thiation: Gas-Phase Structures and Energetics

    NASA Astrophysics Data System (ADS)

    Hamlow, Lucas; Lee, Justin; Rodgers, M. T.; Berden, Giel; Oomens, Jos

    2016-06-01

    The naturally occurring thiated uridine nucleosides, 4-thiouridine (s4Urd) and 2-thiouridine (s2Urd), play important roles in the function and analysis of a variety of RNAs. 2-Thiouridine and its C5 modified analogues are commonly found in tRNAs and are believed to play an important role in codon recognition possibly due to their different structure, which has been shown by NMR to be predominantly C3'-endo. 2-Thiouridine may also play an important role in facilitating nonenzymatic RNA replication and transcription. 4-Thiouridine is a commonly used photoactivatable crosslinker that is often used to study RNA-RNA and RNA-protein cross-linking behavior. Differences in the base pairing between uracil and 4-thiouracil with adenine and guanine are an important factor in their role as a cross linker. The photoactivity of s4Urd may also aid in preventing near-UV lethality in cells. An understanding of their intrinsic structure in the gas-phase may help further elucidate the roles these modified nucleosides play in the regulation of RNAs. In this work, infrared multiple photon dissociation (IRMPD) action spectra of the protonated forms of s2Urd and s4Urd were collected in the IR fingerprint region. Structural information is determined by comparison with theoretical linear IR spectra generated from density functional theory calculations using molecular modeling to generate low-energy candidate structures. Present results are compared with analogous results for the protonated forms of uridine and 2'-deoxyuridine as well as solution phase NMR data and crystal structures.

  9. Gas-phase diffusivity and tortuosity of structured soils.

    PubMed

    Kristensen, Andreas H; Thorbjørn, Anne; Jensen, Maria P; Pedersen, Mette; Moldrup, Per

    2010-06-25

    Modeling gas-phase diffusion of volatile contaminants in the unsaturated zone relies on soil-gas diffusivity models often developed for repacked and structureless soil columns. These suffer from the flaw of not reflecting preferential diffusion through voids and fractures in the soil, thus possibly causing an underestimation of vapor migration towards building foundations and vapor intrusion to indoor environments. We measured the ratio of the gas diffusion coefficient in soil and in free air (D(p)/D(0)) for 42 variously structured, intact, and unsaturated soil cores taken from 6 Danish sites. Whilst the results from structureless fine sand were adequately described using previously proposed models, results that were obtained from glacial clay till and limestone exhibited a dual-porosity behavior. Instead, these data were successfully described using a dual-porosity model for gas-phase diffusivity, considering a presence of drained fractures surrounded by a lower diffusivity matrix. Based on individual model fits, the tortuosity of fractures in till and limestone was found to be highest in samples with a total porosity <40%, suggesting soil compaction to affect the geometry of the fractures. In summary, this study highlights a potential order of magnitude underestimation associated in the use of classical models for prediction of subsurface gas-phase diffusion coefficients in heterogeneous and fractured soils.

  10. Amphipathic Polymers Enable the Study of Functional Membrane Proteins in the Gas Phase

    PubMed Central

    2012-01-01

    Membrane proteins are notoriously challenging to analyze using mass spectrometry (MS) because of their insolubility in aqueous solution. Current MS methods for studying intact membrane proteins involve solubilization in detergent. However, detergents can destabilize proteins, leading to protein unfolding and aggregation, or resulting in inactive entities. Amphipathic polymers, termed amphipols, can be used as a substitute for detergents and have been shown to enhance the stability of membrane proteins. Here, we show the utility of amphipols for investigating the structural and functional properties of membrane proteins using electrospray ionization mass spectrometry (ESI-MS). The functional properties of two bacterial outer-membrane β-barrel proteins, OmpT and PagP, in complex with the amphipol A8-35 are demonstrated, and their structural integrities are confirmed in the gas phase using ESI-MS coupled with ion mobility spectrometry (IMS). The data illustrate the power of ESI-IMS-MS in separating distinct populations of amphipathic polymers from the amphipol–membrane complex while maintaining a conformationally “nativelike” membrane protein structure in the gas phase. Together, the data indicate the potential importance and utility of amphipols for the analysis of membrane proteins using MS. PMID:23072351

  11. Detergent release prolongs the lifetime of native-like membrane protein conformations in the gas-phase.

    PubMed

    Borysik, Antoni J; Hewitt, Dominic J; Robinson, Carol V

    2013-04-24

    Recent studies have suggested that detergents can protect the structure of membrane proteins during their transition from solution to the gas-phase. Here we provide mechanistic insights into this process by interrogating the structures of membrane protein-detergent assemblies in the gas-phase using ion mobility mass spectrometry. We show a clear correlation between the population of native-like protein conformations and the degree of detergent attachment to the protein in the gas-phase. Interrogation of these protein-detergent assemblies, by tandem mass spectrometry, enables us to define the mechanism by which detergents preserve native-like protein conformations in a solvent free environment. We show that the release of detergent is more central to the survival of these conformations than the physical presence of detergent bound to the protein. We propose that detergent release competes with structural collapse for the internal energy of the ion and permits the observation of transient native-like membrane protein conformations that are otherwise lost to structural rearrangement in the gas-phase.

  12. Microwave spectrum and gas phase structure of maleimide

    NASA Astrophysics Data System (ADS)

    Pejlovas, Aaron M.; Oncer, Onur; Kang, Lu; Kukolich, Stephen G.

    2016-01-01

    The rotational spectrum of maleimide was measured in the 5-12 GHz range using a Flygare-Balle type, pulsed-beam Fourier transform microwave spectrometer. Rotational transitions were measured for the parent, all unique singly substituted 13C isotopologues, and an sbnd ND, deuterium substituted isotopologue. The parent (or normal isotopologue) rotational constants, centrifugal distortion constants, and quadrupole coupling constants are A = 6815.3251(12) MHz, B = 2361.85011(64) MHz, C = 1754.32750(64) MHz, DJ = 0.232(24) kHz, DJK = 0.546(54) kHz, 1.5χaa = 2.4227(53) MHz, and 0.25(χbb-χcc) = 1.3679(15) MHz. A best fit gas phase structure was determined using the experimental rotational constants of the isotopologues and some parameters from calculations. The inertial defect is Δ = -0.054 amu Å2, indicating a planar structure for maleimide, with no large amplitude motions observed on the sbnd NH hydrogen atom. Calculations using B3LYP/aug-cc-pVTZ provided rotational constants which are much closer (within 1-2%) to the experimental values compared to the MP2/aug-cc-pVTZ calculated values.

  13. Cryogenic Ion Mobility-Mass Spectrometry: Tracking Ion Structure from Solution to the Gas Phase.

    PubMed

    Servage, Kelly A; Silveira, Joshua A; Fort, Kyle L; Russell, David H

    2016-07-19

    guanidinium ion. Studies on the neuropeptide substance P illustrate the ability of cryo-IM-MS to elucidate information about heterogeneous ion populations. Results show that a kinetically trapped conformer is stabilized by a combination of hydration and specific intramolecular interactions, but upon dehydration, this conformer rearranges to form a thermodynamically favored gas-phase ion conformation. Finally, recent studies on hydration of the protein ubiquitin reveal water-mediated dimerization, thereby illustrating the extension of this approach to studies of large biomolecules. Collectively, these studies illustrate a new dimension to studies of biomolecules, resulting from the ability to monitor snapshots of the structural evolution of ions during the transition from solution to gas phase and provide unparalleled insights into the intricate interplay between competing effects that dictate conformational preferences. PMID:27334393

  14. CIUSuite: A Quantitative Analysis Package for Collision Induced Unfolding Measurements of Gas-Phase Protein Ions.

    PubMed

    Eschweiler, Joseph D; Rabuck-Gibbons, Jessica N; Tian, Yuwei; Ruotolo, Brandon T

    2015-11-17

    Ion mobility-mass spectrometry (IM-MS) is a technology of growing importance for structural biology, providing complementary 3D structure information for biomolecules within samples that are difficult to analyze using conventional analytical tools through the near-simultaneous acquisition of ion collision cross sections (CCSs) and masses. Despite recent advances in IM-MS instrumentation, the resolution of closely related protein conformations remains challenging. Collision induced unfolding (CIU) has been demonstrated as a useful tool for resolving isocrossectional protein ions, as they often follow distinct unfolding pathways when subjected to collisional heating in the gas phase. CIU has been used for a variety of applications, from differentiating binding modes of activation state-selective kinase inhibitors to characterizing the domain structure of multidomain proteins. With the growing utilization of CIU as a tool for structural biology, significant challenges have emerged in data analysis and interpretation, specifically the normalization and comparison of CIU data sets. Here, we present CIUSuite, a suite of software modules designed for the rapid processing, analysis, comparison, and classification of CIU data. We demonstrate these tools as part of a series of workflows for applications in comparative structural biology, biotherapeutic analysis, and high throughput screening of kinase inhibitors. These examples illustrate both the potential for CIU in general protein analysis as well as a demonstration of best practices in the interpretation of CIU data. PMID:26489593

  15. Gas-phase molecular structure and energetics of anionic silicates

    NASA Astrophysics Data System (ADS)

    Gomes, José R. B.; Cordeiro, M. Natália D. S.; Jorge, Miguel

    2008-09-01

    The gas-phase stabilities of linear, branched and cyclic silicates made of up to five silicon atoms were studied with density functional theory (DFT). The starting geometries for the DFT calculations at the B3LYP/6-311+G(2d,2p) level of theory were obtained from classical molecular dynamics simulations. We have observed that geometric parameters and charges are mainly affected by the degree of deprotonation. Charges on Si atoms are also influenced by their degree of substitution. The enthalpy of deprotonation of the neutral species was found to decrease with the size of the molecule, while the average deprotonation enthalpy of highly charged compounds increased with molecular size. Furthermore, the formation of rings in highly charged silicates is enthalpically preferred to chain growth. These observations result from two competing effects: the easier distribution of negative charge in silicates with low charge density and the strong intramolecular repulsions present in silicates with high charge density. As a consequence, highly charged silicates in the gas phase tend to be as small and as highly condensed as possible, which is in line with experimental observations from solution NMR.

  16. Secondary structures of short peptide chains in the gas phase: Double resonance spectroscopy of protected dipeptides

    NASA Astrophysics Data System (ADS)

    Chin, Wutharath; Dognon, Jean-Pierre; Canuel, Clélia; Piuzzi, François; Dimicoli, Iliana; Mons, Michel; Compagnon, Isabelle; von Helden, Gert; Meijer, Gerard

    2005-02-01

    The conformational structure of short peptide chains in the gas phase is studied by laser spectroscopy of a series of protected dipeptides, Ac-Xxx-Phe-NH2, Xxx=Gly, Ala, and Val. The combination of laser desorption with supersonic expansion enables us to vaporize the peptide molecules and cool them internally; IR/UV double resonance spectroscopy in comparison to density functional theory calculations on Ac-Gly-Phe-NH2 permits us to identify and characterize the conformers populated in the supersonic expansion. Two main conformations, corresponding to secondary structures of proteins, are found to compete in the present experiments. One is composed of a doubly γ-fold corresponding to the 27 ribbon structure. Topologically, this motif is very close to a β-strand backbone conformation. The second conformation observed is the β-turn, responsible for the chain reversal in proteins. It is characterized by a relatively weak hydrogen bond linking remote NH and CO groups of the molecule and leading to a ten-membered ring. The present gas phase experiment illustrates the intrinsic folding properties of the peptide chain and the robustness of the β-turn structure, even in the absence of a solvent. The β-turn population is found to vary significantly with the residues within the sequence; the Ac-Val-Phe-NH2 peptide, with its two bulky side chains, exhibits the largest β-turn population. This suggests that the intrinsic stabilities of the 27 ribbon and the β-turn are very similar and that weakly polar interactions occurring between side chains can be a decisive factor capable of controlling the secondary structure.

  17. High resolution ion mobility measurements for gas phase proteins: correlation between solution phase and gas phase conformations

    NASA Astrophysics Data System (ADS)

    Hudgins, Robert R.; Woenckhaus, Jürgen; Jarrold, Martin F.

    1997-11-01

    Our high resolution ion mobility apparatus has been modified by attaching an electrospray source to perform measurements for biological molecules. While the greater resolving power permits the resolution of more conformations for BPTI and cytochrome c, the resolved features are generally much broader than expected for a single rigid conformation. A major advantage of the new experimental configuration is the much gentler introduction of ions into the drift tube, so that the observed gas phase conformations appear to more closely reflect those present in solution. For example, it is possible to distinguish between the native state of cytochrome c and the methanol-denatured form on the basis of the ion mobility measurements; the mass spectra alone are not sensitive enough to detect this change. Thus this approach may provide a quick and sensitive tool for probing the solution phase conformations of biological molecules.

  18. Equilibrium structure of gas phase o-benzyne

    NASA Astrophysics Data System (ADS)

    Groner, Peter; Kukolich, Stephen G.

    2006-01-01

    An equilibrium structure has been derived for o-benzyne from experimental rotational constants of seven isotopomers and vibration-rotation constants calculated from MP2 (full)/6-31G(d) quadratic and cubic force fields. In the case of benzene, this method yields results that are in excellent agreement with those obtained from high quality ab initio force fields. The ab initio-calculated vibrational averaging corrections were applied to the measured A0, B0 and C0 rotational constants and the resulting experimental, near-equilibrium, rotational constants were used in a least squares fit to determine the approximate equilibrium structural parameters. The C-C bond lengths for this equilibrium structure of o-benzyne are, beginning with the formal triple bond (C 1-C 2): 1.255, 1.383, 1.403 and 1.405 Å. The bond angles obtained are in good agreement with most of the recent ab initio predictions.

  19. Probing the glycosidic linkage: secondary structures in the gas phase

    NASA Astrophysics Data System (ADS)

    Simons, John P.; Cristina Stanca-Kaposta, E.; Cocinero, Emilio J.; Liu, B.; Davis, Benjamin G.; Gamblin, David P.; Kroemer, Romano T.

    2008-10-01

    The functional importance of carbohydrates in biological processes, particularly those involving specific molecular recognition, is immense. Characterizing the three-dimensional (3D) structures of carbohydrates and glycoproteins, and their interactions with other molecules, not least the ubiquitous solvent, water, is a key starting point for understanding these processes. The combination of laser-based electronic and vibrational spectroscopy of mass-selected carbohydrate molecules and their hydrated complexes, conducted under molecular beam conditions, with ab initio computation is providing a uniquely powerful means of characterizing 3D carbohydrate conformations; the structures of their hydrated complexes, the hydrogen-bonded networks they support (or which support them); and the factors that determine their conformational and structural preferences.

  20. Gas-Phase Intramolecular Protein Crosslinking via Ion/Ion Reactions: Ubiquitin and a Homobifunctional sulfo-NHS Ester

    NASA Astrophysics Data System (ADS)

    Webb, Ian K.; Mentinova, Marija; McGee, William M.; McLuckey, Scott A.

    2013-05-01

    Gas-phase intra-molecular crosslinking of protein ubiquitin cations has been demonstrated via ion/ion reactions with anions of a homobifunctional N-hydroxysulfosuccinimide (sulfo-NHS) ester reagent. The ion/ion reaction between multiply-protonated ubiquitin and crosslinker monoanions produces a stable, charge-reduced complex. Covalent crosslinking is indicated by the consecutive loss of 2 molecules of sulfo-NHS under ion trap collisional activation conditions. Covalent modification is verified by the presence of covalently crosslinked sequence ions produced by ion-trap collision-induced dissociation of the ion generated from the losses of sulfo-NHS. Analysis of the crosslinked sequence fragments allows for the localization of crosslinked primary amines, enabling proximity mapping of the gas-phase 3-D structures. The presence of two unprotonated reactive sites within the distance constraint of the crosslinker is required for successful crosslinking. The ability to covalently crosslink is, therefore, sensitive to protein charge state. As the charge state increases, fewer reactive sites are available and protein structure is more likely to become extended because of intramolecular electrostatic repulsion. At high charge states, the reagent shows little evidence for covalent crosslinking but does show evidence for `electrostatic crosslinking' in that the binding of the sulfonate groups to the protein is sufficiently strong that backbone cleavages are favored over reagent detachment under ion trap collisional activation conditions.

  1. Gas-phase intramolecular protein crosslinking via ion/ion reactions: ubiquitin and a homobifunctional sulfo-NHS ester.

    PubMed

    Webb, Ian K; Mentinova, Marija; McGee, William M; McLuckey, Scott A

    2013-05-01

    Gas-phase intra-molecular crosslinking of protein ubiquitin cations has been demonstrated via ion/ion reactions with anions of a homobifunctional N-hydroxysulfosuccinimide (sulfo-NHS) ester reagent. The ion/ion reaction between multiply-protonated ubiquitin and crosslinker monoanions produces a stable, charge-reduced complex. Covalent crosslinking is indicated by the consecutive loss of 2 molecules of sulfo-NHS under ion trap collisional activation conditions. Covalent modification is verified by the presence of covalently crosslinked sequence ions produced by ion-trap collision-induced dissociation of the ion generated from the losses of sulfo-NHS. Analysis of the crosslinked sequence fragments allows for the localization of crosslinked primary amines, enabling proximity mapping of the gas-phase 3-D structures. The presence of two unprotonated reactive sites within the distance constraint of the crosslinker is required for successful crosslinking. The ability to covalently crosslink is, therefore, sensitive to protein charge state. As the charge state increases, fewer reactive sites are available and protein structure is more likely to become extended because of intramolecular electrostatic repulsion. At high charge states, the reagent shows little evidence for covalent crosslinking but does show evidence for 'electrostatic crosslinking' in that the binding of the sulfonate groups to the protein is sufficiently strong that backbone cleavages are favored over reagent detachment under ion trap collisional activation conditions. PMID:23463545

  2. Gas Phase Structure of Amino Acids: La-Mb Studies

    NASA Astrophysics Data System (ADS)

    Mata, I. Pena S.; Sanz, M. E.; Vaquero, V.; Cabezas, C.; Perez, C.; Blanco, S.; López, J. C.; Alonso, J. L.

    2009-06-01

    Recent improvements in our laser ablation molecular beam Fourier transform microwave (LA-MB-FTMW) spectrometer such as using Laval-type nozzles and picoseconds Nd:YAG lasers (30 to 150 ps) have allowed a major step forward in the capabilities of this experimental technique as demonstrated by the last results in serine cysteine and threonine^a for which seven, six and seven conformers have been respectively identified. Taking advantage of these improvements we have investigated the natural amino acids metionine, aspartic and glutamic acids and the γ-aminobutyric acid (GABA) with the aim of identify and characterize their lower energy conformers. Searches in the rotational spectra have lead to the identification of seven conformers of metionine, six and five of aspartic and glutamic acids, respectively, and seven for the γ-aminobutyric. These conformers have been unambiguously identified by their spectroscopic constants. In particular the ^{14}N nuclear quadrupole coupling constants, that depend heavily on the orientation of the amino group with respect to the principal inertial axes of the molecule, prove to be a unique tool to distinguish unambigously between conformations with similar rotational constants. For the γ-aminobutyric acid two of the seven observed structures are stablized by an intramolecular interaction n-π*. Two new conformers of proline have been identified together with the two previously observed. J. L. Alonso, C. Pérez, M. E. Sanz, J. C. López, S. Blanco, Phys.Chem.Chem.Phys., 2009, 11, 617. D. B. Atkinson, M. A. Smith, Rev. Sci. Instrum. 1995, 66, 4434 S. Blanco, M. E. Sanz, J. C. López, J. L. Alonso, Proc. Natl. Acad. Sci. USA2007, 104, 20183. M. E. Sanz, S. Blanco, J. C. López, J. L. Alonso, Angew. Chem. Int. Ed.,2008, 120, 6312. A. Lesarri, S. Mata, E. J. Cocinero, S. Blanco, J.C. López, J. L. Alonso, Angew. Chem. Int. Ed. , 2002, 41, 4673

  3. Reagent Cluster Anions for Multiple Gas-Phase Covalent Modifications of Peptide and Protein Cations

    NASA Astrophysics Data System (ADS)

    Prentice, Boone M.; Stutzman, John R.; McLuckey, Scott A.

    2013-07-01

    Multiple gas phase ion/ion covalent modifications of peptide and protein ions are demonstrated using cluster-type reagent anions of N-hydroxysulfosuccinimide acetate (sulfo-NHS acetate) and 2-formyl-benzenesulfonic acid (FBMSA). These reagents are used to selectively modify unprotonated primary amine functionalities of peptides and proteins. Multiple reactive reagent molecules can be present in a single cluster ion, which allows for multiple covalent modifications to be achieved in a single ion/ion encounter and at the `cost' of only a single analyte charge. Multiple derivatizations are demonstrated when the number of available reactive sites on the analyte cation exceeds the number of reagent molecules in the anionic cluster (e.g., data shown here for reactions between the polypeptide [K10 + 3H]3+ and the reagent cluster [5R5Na - Na]-). This type of gas-phase ion chemistry is also applicable to whole protein ions. Here, ubiquitin was successfully modified using an FBMSA cluster anion which, upon collisional activation, produced fragment ions with various numbers of modifications. Data for the pentamer cluster are included as illustrative of the results obtained for the clusters comprised of two to six reagent molecules.

  4. Is it biologically relevant to measure the structures of small peptides in the gas-phase?

    NASA Astrophysics Data System (ADS)

    Barran, Perdita E.; Polfer, Nick C.; Campopiano, Dominic J.; Clarke, David J.; Langridge-Smith, Patrick R. R.; Langley, Ross J.; Govan, John R. W.; Maxwell, Alison; Dorin, Julia R.; Millar, Robert P.; Bowers, Michael T.

    2005-02-01

    Recent developments in sample introduction of biologically relevant molecules have heralded a new era for gas-phase methods of structural determination. One of the biggest challenges is to relate gas-phase structures, often measured in the absence of water and counter ions, with in vivo biologically active structures. An advantage of gas-phase based techniques is that a given peptide can be analysed in a variety of different forms, for example, as a function of charge state, or with additional water molecules. Molecular modelling can provide insight into experimental findings and help elucidate the differences between structural forms. Combining experiment and theory provides a thorough interrogation of candidate conformations. Here two important naturally occurring peptide systems have been examined in detail and results are assessed in terms of their biological significance. The first of these is gonadotropin-releasing hormone (GnRH), a decapeptide which is the central regulator of the reproductive system in vertebrates. We have examined several naturally occurring variants of this peptide using Ion Mobility Mass Spectrometry and Electron Capture Dissociation (ECD) in conjunction with Fourier Transform Ion Cyclotron Mass Spectrometry (FT-ICR-MS). Candidate conformations are modelled using the AMBER force field. Single amino acid changes, for example Gly6 --> Ala6, or Ala6 --> D-Ala6, have observable effects on the gas phase structure of GnRH. It has been shown that evolutionary primary sequence variations are key to the biological activity of GnRH, and it is thought that this is due to different binding affinities at target receptors. This work provides strong evidence that this activity is structurally based. The second system examined is the relationship between the quaternary structure and activity of two novel [beta]-defensins. FT-ICR mass spectrometry has been employed to characterize di-sulphide bridging and dissociation based experiments utilised to

  5. Probing secondary structures of peptide chains using gas phase laser spectroscopy

    NASA Astrophysics Data System (ADS)

    Mons, Michel

    2006-03-01

    A bottom-up approach involving conformer-specific IR studies of short peptide sequences enables us to map the intramolecular interactions that shape the peptide backbone, in particular those H-bonds that are responsible for stability and formation of secondary structures in proteins, like turns or helices. The combination of laser-desorption of solid samples coupled to the efficient cooling in a supersonic expansion makes it possible to isolate in the gas phase the lowest conformations of the energy landscape of small flexible biomolecules. The low temperature achieved enables spectroscopists to record UV spectra in which the contribution of each conformer populated can be distinguished and the corresponding conformation identified using IR/UV double resonance spectroscopy. Data collected are directly comparable to the best quantum chemistry calculations on these species and therefore constitute a severe test for the theoretical methods used. It will be shown how investigation of sequences with an increasing number of building blocks permits to deduce the robust structural trends of a peptide backbone: i) local conformational preference of the backbone in one-residue chains, ii) in capped dipeptides, the competition between a succession of local conformational preferences and overall folded structures, in which a different type of H-bonding scheme, involving distant H-bonding sites along the backbone, takes place: in particular beta-turns, the secondary structure responsible for chain reversals, and finally iii) evidence for the spontaneous helical folding (short 3-10 helix) of three-residue chains will be presented, illustrating the relative weakness of the H-bonding in these molecular assemblies.

  6. Description and control of dissociation channels in gas-phase protein complexes

    NASA Astrophysics Data System (ADS)

    Thachuk, Mark; Fegan, Sarah K.; Raheem, Nigare

    2016-08-01

    Using molecular dynamics simulations of a coarse-grained model of the charged apo-hemoglobin protein complex, this work expands upon our initial report [S. K. Fegan and M. Thachuk, J. Am. Soc. Mass Spectrom. 25, 722-728 (2014)] about control of dissociation channels in the gas phase using specially designed charge tags. Employing a charge hopping algorithm and a range of temperatures, a variety of dissociation channels are found for activated gas-phase protein complexes. At low temperatures, a single monomer unfolds and becomes charge enriched. At higher temperatures, two additional channels open: (i) two monomers unfold and charge enrich and (ii) two monomers compete for unfolding with one eventually dominating and the other reattaching to the complex. At even higher temperatures, other more complex dissociation channels open with three or more monomers competing for unfolding. A model charge tag with five sites is specially designed to either attract or exclude charges. By attaching this tag to the N-terminus of specific monomers, the unfolding of those monomers can be decidedly enhanced or suppressed. In other words, using charge tags to direct the motion of charges in a protein complex provides a mechanism for controlling dissociation. This technique could be used in mass spectrometry experiments to direct forces at specific attachment points in a protein complex, and hence increase the diversity of product channels available for quantitative analysis. In turn, this could provide insight into the function of the protein complex in its native biological environment. From a dynamics perspective, this system provides an interesting example of cooperative behaviour involving motions with differing time scales.

  7. Binding Energies of Protonated Betaine Complexes: A Probe of Zwitterion Structure in the Gas Phase

    PubMed Central

    Price, William D.; Jockusch, Rebecca A.

    2005-01-01

    The dissociation kinetics of proton-bound dimers of betaine with molecules of comparable gas-phase basicity were investigated using blackbody infrared radiative dissociation (BIRD). Threshold dissociation energies were obtained from these data using master equation modeling. For bases that have comparable or higher gas-phase basicity, the binding energy of the protonated base·betaine complex is ~1.4 eV. For molecules that are ~2 kcal/mol or more less basic, the dissociation energy of the complexes is ~1.2 eV. The higher binding energy of the former is attributed to an ion–zwitterion structure which has a much larger ion–dipole interaction. The lower binding energy for molecules that are ~2 kcal/mol or more less basic indicates that an ion–molecule structure is more favored. Semiempirical calculations at both the AM1 and PM3 levels indicate the most stable ion–molecule structure is one in which the base interacts with the charged quaternary ammonium end of betaine. These results indicate that the measurement of binding energies of neutral molecules to biological ions could provide a useful probe for the presence of zwitterions and salt bridges in the gas phase. From the BIRD data, the gas-phase basicity of betaine obtained from the kinetic method is found to be 239.2 ± 1.0 kcal/mol. This value is in excellent agreement with the value of 239.3 kcal/mol (298 K) from ab initio calculations at the MP2/6-31+g** level. The measured value is slightly higher than those reported previously. This difference is attributed to entropy effects. The lower ion internal energy and longer time frame of BIRD experiments should provide values closer to those at standard temperature. PMID:16543945

  8. Dissociation of Multisubunit Protein-Ligand Complexes in the Gas Phase. Evidence for Ligand Migration

    NASA Astrophysics Data System (ADS)

    Zhang, Yixuan; Deng, Lu; Kitova, Elena N.; Klassen, John S.

    2013-10-01

    -ligand complexes in the gas phase depend, not only on the native topology of the complex, but also on structural changes that occur upon collisional activation.

  9. The effect of molecular dynamics sampling on the calculated observable gas-phase structures.

    PubMed

    Tikhonov, Denis S; Otlyotov, Arseniy A; Rybkin, Vladimir V

    2016-07-21

    In this study, we compare the performance of various ab initio molecular dynamics (MD) sampling methods for the calculation of the observable vibrationally-averaged gas-phase structures of benzene, naphthalene and anthracene molecules. Nose-Hoover (NH), canonical and quantum generalized-Langevin-equation (GLE) thermostats as well as the a posteriori quantum correction to the classical trajectories have been tested and compared to the accurate path-integral molecular dynamics (PIMD), static anharmonic vibrational calculations as well as to the experimental gas electron diffraction data. Classical sampling methods neglecting quantum effects (NH and canonical GLE thermostats) dramatically underestimate vibrational amplitudes for the bonded atom pairs, both C-H and C-C, the resulting radial distribution functions exhibit nonphysically narrow peaks. This deficiency is almost completely removed by taking the quantum effects on the nuclei into account. The quantum GLE thermostat and a posteriori correction to the canonical GLE and NH thermostatted trajectories capture most vibrational quantum effects and closely reproduce computationally expensive PIMD and experimental radial distribution functions. These methods are both computationally feasible and accurate and are therefore recommended for calculations of the observable gas-phase structures. A good performance of the quantum GLE thermostat for the gas-phase calculations is encouraging since its parameters have been originally fitted for the condensed-phase calculations. Very accurate molecular structures can be predicted by combining the equilibrium geometry obtained at a high level of electronic structure theory with vibrational amplitudes and corrections calculated using MD driven by a lower level of electronic structure theory.

  10. The effect of molecular dynamics sampling on the calculated observable gas-phase structures.

    PubMed

    Tikhonov, Denis S; Otlyotov, Arseniy A; Rybkin, Vladimir V

    2016-07-21

    In this study, we compare the performance of various ab initio molecular dynamics (MD) sampling methods for the calculation of the observable vibrationally-averaged gas-phase structures of benzene, naphthalene and anthracene molecules. Nose-Hoover (NH), canonical and quantum generalized-Langevin-equation (GLE) thermostats as well as the a posteriori quantum correction to the classical trajectories have been tested and compared to the accurate path-integral molecular dynamics (PIMD), static anharmonic vibrational calculations as well as to the experimental gas electron diffraction data. Classical sampling methods neglecting quantum effects (NH and canonical GLE thermostats) dramatically underestimate vibrational amplitudes for the bonded atom pairs, both C-H and C-C, the resulting radial distribution functions exhibit nonphysically narrow peaks. This deficiency is almost completely removed by taking the quantum effects on the nuclei into account. The quantum GLE thermostat and a posteriori correction to the canonical GLE and NH thermostatted trajectories capture most vibrational quantum effects and closely reproduce computationally expensive PIMD and experimental radial distribution functions. These methods are both computationally feasible and accurate and are therefore recommended for calculations of the observable gas-phase structures. A good performance of the quantum GLE thermostat for the gas-phase calculations is encouraging since its parameters have been originally fitted for the condensed-phase calculations. Very accurate molecular structures can be predicted by combining the equilibrium geometry obtained at a high level of electronic structure theory with vibrational amplitudes and corrections calculated using MD driven by a lower level of electronic structure theory. PMID:27331660

  11. Noble metal alloy clusters in the gas phase derived from protein templates: unusual recognition of palladium by gold.

    PubMed

    Baksi, Ananya; Pradeep, T

    2013-12-21

    Matrix assisted laser desorption ionization of a mixture of gold and palladium adducts of the protein lysozyme (Lyz) produces naked alloy clusters of the type Au24Pd(+) in the gas phase. While a lysozyme-Au adduct forms Au18(+), Au25(+), Au38(+) and Au102(+) ions in the gas phase, lysozyme-Pd alone does not form any analogous cluster. Addition of various transition metal ions (Ag(+), Pt(2+), Pd(2+), Cu(2+), Fe(2+), Ni(2+) and Cr(3+)) in the adducts contributes to drastic changes in the mass spectrum, but only palladium forms alloys in the gas phase. Besides alloy formation, palladium enhances the formation of specific single component clusters such as Au38(+). While other metal ions like Cu(2+) help forming Au25(+) selectively, Fe(2+) catalyzes the formation of Au25(+) over all other clusters. Gas phase cluster formation occurs from protein adducts where Au is in the 1+ state while Pd is in the 2+ state. The creation of alloys in the gas phase is not affected whether a physical mixture of Au and Pd adducts or a Au and Pd co-adduct is used as the precursor. The formation of Au cores and AuPd alloy cores of the kind comparable to monolayer protected clusters implies that naked clusters themselves may be nucleated in solution. PMID:24146135

  12. Noble metal alloy clusters in the gas phase derived from protein templates: unusual recognition of palladium by gold.

    PubMed

    Baksi, Ananya; Pradeep, T

    2013-12-21

    Matrix assisted laser desorption ionization of a mixture of gold and palladium adducts of the protein lysozyme (Lyz) produces naked alloy clusters of the type Au24Pd(+) in the gas phase. While a lysozyme-Au adduct forms Au18(+), Au25(+), Au38(+) and Au102(+) ions in the gas phase, lysozyme-Pd alone does not form any analogous cluster. Addition of various transition metal ions (Ag(+), Pt(2+), Pd(2+), Cu(2+), Fe(2+), Ni(2+) and Cr(3+)) in the adducts contributes to drastic changes in the mass spectrum, but only palladium forms alloys in the gas phase. Besides alloy formation, palladium enhances the formation of specific single component clusters such as Au38(+). While other metal ions like Cu(2+) help forming Au25(+) selectively, Fe(2+) catalyzes the formation of Au25(+) over all other clusters. Gas phase cluster formation occurs from protein adducts where Au is in the 1+ state while Pd is in the 2+ state. The creation of alloys in the gas phase is not affected whether a physical mixture of Au and Pd adducts or a Au and Pd co-adduct is used as the precursor. The formation of Au cores and AuPd alloy cores of the kind comparable to monolayer protected clusters implies that naked clusters themselves may be nucleated in solution.

  13. UV/Vis Action Spectroscopy and Structures of Tyrosine Peptide Cation Radicals in the Gas Phase.

    PubMed

    Viglino, Emilie; Shaffer, Christopher J; Tureček, František

    2016-06-20

    We report the first application of UV/Vis photodissociation action spectroscopy for the structure elucidation of tyrosine peptide cation radicals produced by oxidative intramolecular electron transfer in gas-phase metal complexes. Oxidation of Tyr-Ala-Ala-Ala-Arg (YAAAR) produces Tyr-O radicals by combined electron and proton transfer involving the phenol and carboxyl groups. Oxidation of Ala-Ala-Ala-Tyr-Arg (AAAYR) produces a mixture of cation radicals involving electron abstraction from the Tyr phenol ring and N-terminal amino group in combination with hydrogen-atom transfer from the Cα positions of the peptide backbone. PMID:27159034

  14. The structure of oxotitanium phthalocyanine: a gas-phase electron diffraction and computational study.

    PubMed

    Zakharov, Alexander V; Shlykov, Sergei A; Zhabanov, Yuriy A; Girichev, Georgy V

    2009-05-14

    The gas-phase molecular structure of oxotitanium phthalocyanine (TiOPc) has been studied by a synchronous gas electron diffraction and mass spectrometric experiment, and density functional theory calculations using the B3LYP hybrid method and cc-pVTZ basis sets. The molecule has an equilibrium structure of C4v symmetry with a convex macrocycle. The titanium atom is out-of-the-plane of the four central nitrogen atoms and forms a square pyramid with them, with the following parameters: r(Ti-N)=2.090(5) A, r(NN)=2.813(9) A (the side of the pyramid base), z(Ti)-z(N)=0.614 A (the height of the pyramid). Compared to solid-state crystal structures, the Ti-O distance in gas-phase TiOPc is shortened and the Ti-N distance is elongated, which can be attributed to significant intermolecular interaction in the crystals. PMID:19421550

  15. Infrared Laser Activation of Soluble and Membrane Protein Assemblies in the Gas Phase.

    PubMed

    Mikhailov, Victor A; Liko, Idlir; Mize, Todd H; Bush, Matthew F; Benesch, Justin L P; Robinson, Carol V

    2016-07-19

    Collision-induced dissociation (CID) is the dominant method for probing intact macromolecular complexes in the gas phase by means of mass spectrometry (MS). The energy obtained from collisional activation is dependent on the charge state of the ion and the pressures and potentials within the instrument: these factors limit CID capability. Activation by infrared (IR) laser radiation offers an attractive alternative as the radiation energy absorbed by the ions is charge-state-independent and the intensity and time scale of activation is controlled by a laser source external to the mass spectrometer. Here we implement and apply IR activation, in different irradiation regimes, to study both soluble and membrane protein assemblies. We show that IR activation using high-intensity pulsed lasers is faster than collisional and radiative cooling and requires much lower energy than continuous IR irradiation. We demonstrate that IR activation is an effective means for studying membrane protein assemblies, and liberate an intact V-type ATPase complex from detergent micelles, a result that cannot be achieved by means of CID using standard collision energies. Notably, we find that IR activation can be sufficiently soft to retain specific lipids bound to the complex. We further demonstrate that, by applying a combination of collisional activation, mass selection, and IR activation of the liberated complex, we can elucidate subunit stoichiometry and the masses of specifically bound lipids in a single MS experiment.

  16. Gas-phase ion/ion reactions of peptides and proteins: acid/base, redox, and covalent chemistries.

    PubMed

    Prentice, Boone M; McLuckey, Scott A

    2013-02-01

    Gas-phase ion/ion reactions are emerging as useful and flexible means for the manipulation and characterization of peptide and protein biopolymers. Acid/base-like chemical reactions (i.e., proton transfer reactions) and reduction/oxidation (redox) reactions (i.e., electron transfer reactions) represent relatively mature classes of gas-phase chemical reactions. Even so, especially in regards to redox chemistry, the widespread utility of these two types of chemistries is undergoing rapid growth and development. Additionally, a relatively new class of gas-phase ion/ion transformations is emerging which involves the selective formation of functional-group-specific covalent bonds. This feature details our current work and perspective on the developments and current capabilities of these three areas of ion/ion chemistry with an eye towards possible future directions of the field.

  17. Carbonyl Diisocyanate CO(NCO)2: Synthesis and Structures in Solid State and Gas Phase.

    PubMed

    Klapötke, Thomas M; Krumm, Burkhard; Rest, Sebastian; Scharf, Regina; Schwabedissen, Jan; Stammler, Hans-Georg; Mitzel, Norbert W

    2016-07-01

    A modified synthesis for carbonyl diisocyanate, CO(NCO)2, starting from trichloroisocyanuric acid and diphosgene is described. In addition to the previously reported (13)C NMR resonances, the (15)N NMR shift is determined for the first time. The structure in the solid state was determined by X-ray diffraction (XRD) on in situ grown crystals, that in the gas phase was experimentally determined by electron diffraction (GED) and for single molecules theoretically by quantum-chemical calculations. The structures are compared and discussed with related systems. Quantum-chemical calculations as well as GED and XRD prove syn-syn to be the conformation of lowest energy. In quantum-chemical calculations and GED the presence of a syn-anti conformer was confirmed and the structure of this conformer was determined.

  18. Infrared Action Spectroscopy of Low-Temperature Neutral Gas-Phase Molecules of Arbitrary Structure.

    PubMed

    Yatsyna, Vasyl; Bakker, Daniël J; Salén, Peter; Feifel, Raimund; Rijs, Anouk M; Zhaunerchyk, Vitali

    2016-09-01

    We demonstrate a technique for IR action spectroscopy that enables measuring IR spectra in a background-free fashion for low-temperature neutral gas-phase molecules of arbitrary structure. The method is exemplified experimentally for N-methylacetamide molecules in the mid-IR spectral range of 1000-1800  cm^{-1}, utilizing the free electron laser FELIX. The technique involves the resonant absorption of multiple mid-IR photons, which induces molecular dissociation. The dissociation products are probed with 10.49 eV vacuum ultraviolet photons and analyzed with a mass spectrometer. We also demonstrate the capability of this method to record, with unprecedented ease, mid-IR spectra for the molecular associates, such as clusters and oligomers, present in a molecular beam. In this way the mass-selected spectra of low-temperature gas-phase dimers and trimers of N-methylacetamide are measured in the full amide I-III range.

  19. Infrared Action Spectroscopy of Low-Temperature Neutral Gas-Phase Molecules of Arbitrary Structure.

    PubMed

    Yatsyna, Vasyl; Bakker, Daniël J; Salén, Peter; Feifel, Raimund; Rijs, Anouk M; Zhaunerchyk, Vitali

    2016-09-01

    We demonstrate a technique for IR action spectroscopy that enables measuring IR spectra in a background-free fashion for low-temperature neutral gas-phase molecules of arbitrary structure. The method is exemplified experimentally for N-methylacetamide molecules in the mid-IR spectral range of 1000-1800  cm^{-1}, utilizing the free electron laser FELIX. The technique involves the resonant absorption of multiple mid-IR photons, which induces molecular dissociation. The dissociation products are probed with 10.49 eV vacuum ultraviolet photons and analyzed with a mass spectrometer. We also demonstrate the capability of this method to record, with unprecedented ease, mid-IR spectra for the molecular associates, such as clusters and oligomers, present in a molecular beam. In this way the mass-selected spectra of low-temperature gas-phase dimers and trimers of N-methylacetamide are measured in the full amide I-III range. PMID:27661721

  20. Gas-Phase Protein Inner-Shell Spectroscopy by Coupling an Ion Trap with a Soft X-ray Beamline.

    PubMed

    Milosavljević, Aleksandar R; Canon, Francis; Nicolas, Christophe; Miron, Catalin; Nahon, Laurent; Giuliani, Alexandre

    2012-05-01

    C, N, and O near-edge ion yield spectroscopy of 8+ selected electrosprayed cations of cytochrome c protein (12 kDa) has been performed by coupling a linear quadrupole ion trap with a soft X-ray beamline. The photoactivation tandem mass spectra were recorded as a function of the photon energy. Photoionization of the precursor, accompanied by CO2 loss, is the dominant relaxation process, showing high photoion stability following direct or resonant photoionization. The partial ion yields extracted from recorded mass spectra show significantly different behaviors for single and double ionization channels, which can be qualitatively explained by different Auger decay mechanisms. However, the single ionization spectra reveal characteristic structures when compared to existing near-edge X-ray absorption fine structure (NEXAFS) spectra from thin films of peptides and proteins. Therefore, the present experiment opens up new avenues for near-edge X-ray spectroscopy of macromolecules in the gas phase, overcoming the radiation damage issue or the environmental effects as due to the surface, intermolecular interactions, and solvent.

  1. Electronic Structure and Gas-Phase Behaviour of the Heaviest Elements

    SciTech Connect

    Pershina, V.; Anton, J.; Jacob, T.; Borschevsky, A.

    2010-04-30

    Electronic structures and gas-phase adsorption behaviour of the heaviest elements 112, 113 and 114 and of their lighter homologs Hg, Tl and Pb is studied on the basis of ab initio Dirac-Coulomb atomic and four-component Density Functional Theory molecular and cluster calculations. The heaviest elements were shown to have low adsorption enthalpies on Teflon and should, therefore, be well transported through Teflon capillaries from the target chamber to the chemistry set up. Adsorption enthalpies of these elements on the Au(111) surface are predicted as -44.5 kJ/mol, -158.6 kJ/mol and -68.5 kJ/mol, respectively, giving the following sequence in the adsorption temperatures 113>114>112.

  2. Electroscopy Ionization Photoelectron Spectroscopy: Probing the Electronic Structure of Inorganic Metal Complexes in the Gas Phase

    SciTech Connect

    Waters, Tom; Wang, Xue B.; Wang, Lai S.

    2007-02-01

    The coupling of electrospray to photoelectron spectroscopy has allowed a number of negatively charged solution phase transition metal complexes to be transferred to the gas phase and studied by photoelectron spectroscopy for the first time. Experiments have been performed on a range of species, including classic square-planar and octahedral transition-metal halide complexes, metal-metal bonded species, transition metal bis(dithiolene) centers and a variety of mononuclear and polynuclear iron-sulfur clusters that are related to important bioinorganic centers. The studies have provided detailed information about the electronic structure and molecular orbital energy levels of these species, allowing for direct comparison with theoretical calculations, and providing insight into their intrinsic redox properties in the absence of solvation.

  3. Posttranslational modification of Birch and Ragweed allergen proteins by common gas phase pollutants, NO2 and O3

    NASA Astrophysics Data System (ADS)

    Mahmood, M. A.; Pope, F.; Bloss, W.

    2015-12-01

    The global incidence of hay fever has been rising for decades, however, the underlying reasons behind this rise remain unclear. It is hypothesized that exposure of pollen to common gas phase pollutants, such as nitrogen dioxide (NO2) and ozone (O3), increases the allergenicity of the pollen and thus increases hay fever incidence. Since atmospheric pollutants tend to have greater concentrations within urban areas (in particular NO2) the hypothesis suggests that greater allergenicity should occur in urban areas. Indeed, several studies do suggest higher hay fever incidence within urban areas compared to rural areas. Previous published work suggests a link between increased allergies with changes in the chemical composition of the pollen protein via posttranslational modification of the protein. This study investigates the posttranslational modification of two highly allergenic pollen species (Birch and Ragweed) that are common in Europe. Within the laboratory, we expose pollen grains to atmospherically relevant exposures of gas phase NO2, O3 and other common gas phase oxidants under a range of environmentally relevant conditions. The effects of the environmentally relevant exposures on the biochemistry of the pollen grains were probed using a proteomic approach (liquid chromatography coupled ultra-high resolution spectrometer). Our findings indicate the interaction between gas phase pollutants and pollen cause protein specific modifications; in particular, nitration occurs upon tyrosine residues and nitrosylation on cysteine residues. Possibly, these modifications may affect the immune response of the pollen protein, which may suggest a possible reason for increased allergies in reaction to such biologically altered protein. The laboratory-derived results will be supported with a time series analysis of asthma incidence rates for the London area, which take into account the pollen count, and pollutant concentrations. The implications of the results will be discussed

  4. Hydrogen-bonded glycine-HCN complexes in gas phase: structure, energetics, electric properties and cooperativity

    NASA Astrophysics Data System (ADS)

    Machado da Silva, Arnaldo; Chakrabarty, Sumana; Chaudhuri, Puspitapallab

    2015-03-01

    Twelve hydrogen-bonded complexes of glycine and hydrogen cyanide have been studied using high-level quantum-chemical calculations in gas phase. In particular, six 1:1 glycine-HCN dimers and six 1:2 glycine-HCN trimers have been considered. Besides the characteristics of the hydrogen bonds and their effect on molecular structure and energetics, several molecular electric properties have been calculated utilising two different models: MP2/6-31++G(d,p) and DFT-B3LYP/6-31++G(d,p). Although the structural parameters calculated by the two models are similar, equilibrium electronic energies of the clusters show model dependence. The lowest energy dimer is same in both the models which is ca. 3.0 kcal/mol more stable than the highest energy dimer. However, the lowest energy trimer is different in two methods. The energetic difference of stability between the highest and lowest trimer is 4.2 kcal/mol (4.4 kcal/mol) at an MP2 (B3LYP) level of calculation. The bond angles of glycine, in particular, are quite sensitive to the hydrogen-bond formation. Four out of six trimers are found to be strongly cooperative in both the models. Significant changes of dipole moments and polarisabilities of isolated glycine and hydrogen cyanide are observed due to the formation of hydrogen bonding. The Rayleigh scattering intensities of all clusters are much larger than those of their constituent monomers.

  5. Mass spectrometric evaluation of the gas phase structure of noncovalent quadruplex DNA obtained by electrospray ionization

    SciTech Connect

    Edmonds, C.G.; Cheng, Xueheng; Bakhtiar, R.; Van Orden, S.; Smith, R.D.; Schlegel, C.; Camp, D.G. II

    1994-12-31

    A number of quanine-rich DNA sequences have been recognized which assemble into quadrupole-helical non-Watson/Crick hybridized structures. These sequences have been localized in a number of key regions in chromosomal DNA including telomers and transcriptional promoters. The preservation of this tetrameric association in the gas phase following electrospray ionization (ESI) has been reported in this laboratory. The authors have extended these studies by the preparation of four candidate quadruplex oligomers. Three of these (I, 5{prime}-dCGC GGG GCG-3{prime}; II, 5{prime}dCGC GGGG GCG-3{prime} and III, 5{prime}-dCGC GGGGG GCG-3{prime}) differ in the number of quanine residues available for G-quartet stacking in the quadruplex array and a fourth (HG, 5{prime}-dCGC AGGG GCG03{prime}) is a sequence prominent in human telomeric DNA. During their preparation, the authors observed remarkable stability of the multimeric species in the condensed phase including intact migration in HPLC under apparently {open_quotes}denaturing{close_quotes} conditions. Under standard conditions (aqueous solution of oligonucleotide samples and nozzle-skimmer interface) on a linear quadrupole mass spectrometer oligonucleotide samples showed the typical distribution of charge states for unassociated oligonucleotides. ESI from phosphate-EDTA buffered solutions with the utilization of a capillary/skimmer interface arrangement which provides mild conditions for transfer of ions through the atmosphere/vacuum interface afforded spectra which show prominent contributions from species with quadrupole stoichiometry together monomeric materials.

  6. Structural study of methyl isonicotinate by gas phase electron diffraction combined with ab initio calculations

    NASA Astrophysics Data System (ADS)

    Kiyono, Hajime; Kuze, Nobuhiko; Fujiwara, Hideo; Takeuchi, Hiroshi; Egawa, Toru; Konaka, Shigehiro

    1996-02-01

    The molecular structure of methyl isonicotinate was studied by gas phase electron diffraction combined with ab initio calculations. The molecular skeleton was assumed to be planar. The determined values of principal structure parameters ( rg and ∠ α) are as follows: r( NC) = 1.343(5) Å, r( C…C) ring = 1.401(3) Å, r( Cγ C) = 1.499(9) Å, r( C O) = 1.205(5) Å, r( C( O) O) = 1.331(8) Å, r( OC Me) = 1.430(8) Å, = 1.103(10) Å, ∠CNC = 117.6(9)°, ∠C βC γC β = 118.7(9)°, ∠C β,trans C γC(O) = 118.6(12), ∠C γCO = 121.4(12)°, ∠C γCO = 114.2(10)°, ∠COC = 115.4(15)°, where angled brackets denote average values and C γ,trans denotes the carbon atom which is trans to the carbonyl oxygen atom. Values in parentheses are the estimated limits of error (3σ) referring to the last significant digit. The structure of the ring in methyl isonicotinate agrees with that of pyridine within experimental error. In contrast, the structure parameters of the COOCH 3 group are significantly different from those of methyl acrylate and methyl acetate. These differences have been discussed in terms of hyperconjugation and steric effects.

  7. Measuring the hydrogen/deuterium exchange of proteins at high spatial resolution by mass spectrometry: overcoming gas-phase hydrogen/deuterium scrambling.

    PubMed

    Rand, Kasper D; Zehl, Martin; Jørgensen, Thomas J D

    2014-10-21

    acidic conditions where the amide hydrogen exchange rate is slowed by many orders of magnitude). The ability to localize the individual deuterated residues (the spatial resolution) is determined by the size (typically ∼7-15 residues) and the number of peptic peptides. These peptides provide a relatively coarse-grained picture of the protein dynamics. A fundamental understanding of the relationship between protein function/dysfunction and conformational dynamics requires in many cases higher resolution and ultimately single-residue resolution. In this Account, we summarize our efforts to achieve single-residue deuterium levels in proteins by electron-based or laser-induced gas-phase fragmentation methods. A crucial analytical requirement for this approach is that the pattern of deuterium labeling from solution is retained in the gas-phase fragment ions. It is therefore essential to control and minimize any occurrence of gas-phase randomization of the solution deuterium label (H/D scrambling) during the MS experiment. For this purpose, we have developed model peptide probes to accurately measure the onset and extent of H/D scrambling. Our analytical procedures to control the occurrence of H/D scrambling are detailed along with the physical parameters that induce it during MS analysis. In light of the growing use of gas-phase dissociation experiments to measure the HDX of proteins in order to obtain a detailed characterization and understanding of the dynamic conformations and interactions of proteins at the molecular level, we discuss the perspectives and challenges of future high-resolution HDX-MS methodology.

  8. Gas Phase Spectra and Structural Determination of Glucose 6 Phosphate Using Cryogenic Ion Vibrational Spectroscopy

    NASA Astrophysics Data System (ADS)

    Kregel, Steven J.; Voss, Jonathan; Marsh, Brett; Garand, Etienne

    2014-06-01

    Glucose-6-Phosphate (G6P) is one member of a class of simple phosphorylated sugars that are relevant in biological processes. We have acquired a gas phase infrared spectrum of G6P- using cryogenic ion vibrational spectroscopy (CIVS) in a home-built spectrometer. The experimental spectrum was compared with calculated vibrational spectra from a systematic conformer search. For both of the α and β anomers, results show that only the lowest energy conformers are present in the gas phase. If spectral signatures for similar sugars could be cataloged, it would allow for conformer-specific determination of mixture composition, for example, for glycolyzation processes.

  9. Toluene gas phase biofiltration by Paecilomyces lilacinus and isolation and identification of a hydrophobin protein produced thereof.

    PubMed

    Vigueras, Gabriel; Shirai, Keiko; Martins de Souza, Daniel; Martins, Daniel; Franco, Telma Teixeira; Fleuri, Luciana Francisco; Revah, Sergio

    2008-08-01

    Paecilomyces lilacinus consumed toluene as the sole carbon source in a gas-phase biofilter packed with perlite obtaining an average elimination capacity of 50 g m(-3) h(-1), a removal efficiency of 53%, and a final biomass of 31.6 mg biomass g dry support(-1). Hydrophobin proteins from the mycelium produced in the biofilter were purified by formic acid extraction and precipitated by electrobubbling, and the molecular weight was found to be 10.6 +/- 0.3 kDa. The peptide mass fingerprinting analysis of the purified hydrophobin by matrix-assisted laser desorption/ionization time-of-flight resulted in the identification of two peptides that presented high homology with sequences of class I hydrophobin proteins from other ascomycetous fungi when compared against the National Center for Biotechnology Information database. The yield of hydrophobin (PLHYD) from P. lilacinus was 1.1 mg PLHYD g biomass(-1). These proteins modified the hydrophobicity of Teflon by lowering the contact angle from 130.1 (+/-2) degrees to 57.0 (+/-5) degrees supporting hot sodium dodecyl sulfate washing. This work is the first report about biodegradation of toluene by the nematophagous fungus P. lilacinus in a gas-phase biofilter and the identification of its hydrophobin protein.

  10. An enormous vibrational motion: the gas-phase structure of dimethyl-bis(methoxyethynyl) germanium.

    PubMed

    Borisenko, Konstantin B; Yezhov, Roman N; Gruener, Sergej V; Robertson, Heather E; Rankin, David W H

    2004-11-21

    The structure of dimethyl-bis(methoxyethynyl) germanium has been determined in the gas phase by electron diffraction utilising flexible restraints from quantum chemical calculations. Theoretical methods (B3LYP/6-311+G* and MP2/6-311+G*) predict a low barrier to rotation of the methoxy groups in the molecule in addition to low-frequency vibrations of the long ethynyl chains. In the equilibrium structure the Ge-C[triple bond]C angles of the two methoxyethynyl fragments in the molecule are computed to deviate by up to 4 degrees from the linear arrangement. As a consequence of low-frequency large-amplitude vibrational motion the experimental structure of these fragments without applying vibrational corrections deviates considerably from linearity, while the structure corrected for vibrational effects using the harmonic approximation and taking into account a non-linear transformation between internal and Cartesian coordinates (r(h1)) shows closer agreement with theory. The main experimental structural parameters of dimethyl-bis(methoxyethynyl) germanium (r(h1)) are: r(Ge-C)(mean), 192.5(1) pm; DeltaGeC =r(Ge-C(methyl))-r(Ge-C(ethynyl)), 4.5(5) pm, r(C[triple bond]C)(mean), 122.8(2) pm; r(C-O)(mean), 138.9(3) pm; DeltaCO =r(C(methyl)-O)-r(C(ethynyl)-O), 14.5(2) pm, r(C-H)(mean), 109.1(4) pm; [angle](X-C-H)(mean)(X = Ge,O), 109(1) degree; [angle]C(ethynyl)-Ge-C(ethynyl), 108.1(4) degree; [angle]C(methyl)-Ge-C(methyl), 113.4(5) degree; [angle]Ge-C[triple bond]C, 163(1) degree; [angle]C[triple bond]C-O, 176(2) degree; [angle]C-O-C, 115.2(6) degree; methoxy group torsion, tau, 36(9) degree from the position in which the C-O bond eclipses the further Ge-C(ethynyl) bond. PMID:15540132

  11. Gas-Phase Structures of Ketene and Acetic Acid from Acetic Anhydride Using Very-High-Temperature Gas Electron Diffraction.

    PubMed

    Atkinson, Sandra J; Noble-Eddy, Robert; Masters, Sarah L

    2016-03-31

    The gas-phase molecular structure of ketene has been determined using samples generated by the pyrolysis of acetic anhydride (giving acetic acid and ketene), using one permutation of the very-high-temperature (VHT) inlet nozzle system designed and constructed for the gas electron diffraction (GED) apparatus based at the University of Canterbury. The gas-phase structures of acetic anhydride, acetic acid, and ketene are presented and compared to previous electron diffraction and microwave spectroscopy data to show improvements in data extraction and manipulation with current methods. Acetic anhydride was modeled with two conformers, rather than a complex dynamic model as in the previous study, to allow for inclusion of multiple pyrolysis products. The redetermined gas-phase structure of acetic anhydride (obtained using the structure analysis restrained by ab initio calculations for electron diffraction method) was compared to that from the original study, providing an improvement on the description of the low vibrational torsions compared to the dynamic model. Parameters for ketene and acetic acid (both generated by the pyrolysis of acetic anhydride) were also refined with higher accuracy than previously reported in GED studies, with structural parameter comparisons being made to prior experimental and theoretical studies. PMID:26916368

  12. Gas-Phase Structures of Ketene and Acetic Acid from Acetic Anhydride Using Very-High-Temperature Gas Electron Diffraction.

    PubMed

    Atkinson, Sandra J; Noble-Eddy, Robert; Masters, Sarah L

    2016-03-31

    The gas-phase molecular structure of ketene has been determined using samples generated by the pyrolysis of acetic anhydride (giving acetic acid and ketene), using one permutation of the very-high-temperature (VHT) inlet nozzle system designed and constructed for the gas electron diffraction (GED) apparatus based at the University of Canterbury. The gas-phase structures of acetic anhydride, acetic acid, and ketene are presented and compared to previous electron diffraction and microwave spectroscopy data to show improvements in data extraction and manipulation with current methods. Acetic anhydride was modeled with two conformers, rather than a complex dynamic model as in the previous study, to allow for inclusion of multiple pyrolysis products. The redetermined gas-phase structure of acetic anhydride (obtained using the structure analysis restrained by ab initio calculations for electron diffraction method) was compared to that from the original study, providing an improvement on the description of the low vibrational torsions compared to the dynamic model. Parameters for ketene and acetic acid (both generated by the pyrolysis of acetic anhydride) were also refined with higher accuracy than previously reported in GED studies, with structural parameter comparisons being made to prior experimental and theoretical studies.

  13. Imaging molecular structure through femtosecond photoelectron diffraction on aligned and oriented gas-phase molecules.

    PubMed

    Boll, Rebecca; Rouzée, Arnaud; Adolph, Marcus; Anielski, Denis; Aquila, Andrew; Bari, Sadia; Bomme, Cédric; Bostedt, Christoph; Bozek, John D; Chapman, Henry N; Christensen, Lauge; Coffee, Ryan; Coppola, Niccola; De, Sankar; Decleva, Piero; Epp, Sascha W; Erk, Benjamin; Filsinger, Frank; Foucar, Lutz; Gorkhover, Tais; Gumprecht, Lars; Hömke, André; Holmegaard, Lotte; Johnsson, Per; Kienitz, Jens S; Kierspel, Thomas; Krasniqi, Faton; Kühnel, Kai-Uwe; Maurer, Jochen; Messerschmidt, Marc; Moshammer, Robert; Müller, Nele L M; Rudek, Benedikt; Savelyev, Evgeny; Schlichting, Ilme; Schmidt, Carlo; Scholz, Frank; Schorb, Sebastian; Schulz, Joachim; Seltmann, Jörn; Stener, Mauro; Stern, Stephan; Techert, Simone; Thøgersen, Jan; Trippel, Sebastian; Viefhaus, Jens; Vrakking, Marc; Stapelfeldt, Henrik; Küpper, Jochen; Ullrich, Joachim; Rudenko, Artem; Rolles, Daniel

    2014-01-01

    This paper gives an account of our progress towards performing femtosecond time-resolved photoelectron diffraction on gas-phase molecules in a pump-probe setup combining optical lasers and an X-ray free-electron laser. We present results of two experiments aimed at measuring photoelectron angular distributions of laser-aligned 1-ethynyl-4-fluorobenzene (C(8)H(5)F) and dissociating, laser-aligned 1,4-dibromobenzene (C(6)H(4)Br(2)) molecules and discuss them in the larger context of photoelectron diffraction on gas-phase molecules. We also show how the strong nanosecond laser pulse used for adiabatically laser-aligning the molecules influences the measured electron and ion spectra and angular distributions, and discuss how this may affect the outcome of future time-resolved photoelectron diffraction experiments.

  14. Controlling hydrogen scrambling in multiply charged protein ions during collisional activation: implications for top-down hydrogen/deuterium exchange MS utilizing collisional activation in the gas phase.

    PubMed

    Abzalimov, Rinat R; Kaltashov, Igor A

    2010-02-01

    Hydrogen exchange in solution combined with ion fragmentation in the gas phase followed by MS detection emerged in recent years as a powerful tool to study higher order protein structure and dynamics. However, a certain type of ion chemistry in the gas phase, namely, internal rearrangement of labile hydrogen atoms (the so-called hydrogen scrambling), is often cited as a factor limiting the utility of this experimental technique. Although several studies have been carried out to elucidate the roles played by various factors in the occurrence and the extent of hydrogen scrambling, there is still no consensus as to what experimental protocol should be followed to avoid or minimize it. In this study we employ fragmentation of mass-selected subpopulations of protein ions to assess the extent of internal proton mobility prior to dissociation. A unique advantage of tandem MS is that it not only provides a means to map the deuterium content of protein ions whose overall levels of isotope incorporation can be precisely defined by controlling the mass selection window, but also correlates this spatial isotope distribution with such global characteristic as the protein ion charge state. Hydrogen scrambling does not occur when the charge state of the precursor protein ions selected for fragmentation is high. Fragment ions derived from both N- and C-terminal parts of the protein are equally unaffected by scrambling. However, spatial distribution of deuterium atoms obtained by fragmenting low-charge-density protein ions is consistent with a very high degree of scrambling prior to the dissociation events. The extent of hydrogen scrambling is also high when multistage fragmentation is used to probe deuterium incorporation locally. Taken together, the experimental results provide a coherent picture of intramolecular processes occurring prior to the dissociation event and provide guidance for the design of experiments whose outcome is unaffected by hydrogen scrambling.

  15. Gas-phase structures and thermochemistry of neutral histidine and its conjugated acid and base.

    PubMed

    Riffet, Vanessa; Bouchoux, Guy

    2013-04-28

    Extensive exploration of the conformational space of neutral, protonated and deprotonated histidine has been conducted at the G4MP2 level. Theoretical protonation and deprotonation thermochemistry as well as heats of formation of gaseous histidine and its ionized forms have been calculated at the G4 level considering either the most stable conformers or an equilibrium population of conformers at 298 K. These theoretical results were compared to evaluated experimental determinations. Recommended proton affinity and protonation entropy deduced from these comparisons are PA(His) = 980 kJ mol(-1) and ΔpS(His) ∼ 0 J mol(-1) K(-1), thus leading to a gas-phase basicity value of GB(His) = 947.5 kJ mol(-1). Similarly, gas phase acidity parameters are ΔacidH(o)(His) = 1373 kJ mol(-1), ΔacidS(His) ∼ 10 J mol(-1) K(-1) and ΔacidG(o)(His) = 1343 kJ mol(-1). Computed G4 heats of formation values are equal to -290, 265 and -451 kJ mol(-1) for gaseous neutral histidine and its protonated and deprotonated forms, respectively. The present computational data correct, and complete, previous thermochemical parameter estimates proposed for gas-phase histidine and its acido-basic properties.

  16. Structure of olefin-imidacloprid and gas-phase fragmentation chemistry of its protonated form.

    PubMed

    Fusetto, Roberto; White, Jonathan M; Hutton, Craig A; O'Hair, Richard A J

    2016-02-01

    One of the major insect metabolites of the widely used neonicotinoid insecticide imidacloprid, 1 (1-[(6-chloro-3-pyridinyl)methyl]-N-nitro-1H-imidazol-2-amine), is the olefin 2. To better understand how the structure of olefin 2 relates to the gas-phase fragmentation of its protonated form, 2H(+), X-ray crystallography, tandem mass spectrometry experiments and DFT calculations were carried out. Olefin 2 was found to be in a tautomeric form where the proton is on the N(1) position of the imidazole ring and forms a hydrogen bond to one of the oxygen atoms of the coplanar nitroamine group. Under conditions of low-energy collision-induced dissociation (CID) in a linear ion trap, 2H(+), formed via electrospray ionization (ESI), fragments via a major loss of water, together with minor competing losses of HNO2 and NO2•.This contrasts with 1H+, which mainly undergoes bond homolysis via NO2• loss. Thus, installation of the double bond in 2 plays a key role in facilitating the loss of water. DFT calculations, carried out using the B3LYP/6-311G++(d,p) level of theory, revealed that loss of water was energetically more favourable compared to HNO2 and NO2• loss. Three multistep, energetically accessible mechanisms were identified for loss of water from 2H(+), and these have the following barriers: (I) direct proton transfer from N(5) of the pyridine to O(1) on the NO2 group (119 kJ mol(-1)); (II) rotation of the N(2)-N(4) bond (117 kJ mol(-1)); (III) 1,3-intramolecular proton transfer between the two oxygen atoms of the NO2 group (145 kJ mol(-1)). Given that the lowest barrier for the losses of HNO2 and NO2• is 156 kJ mol(-1), it is likely that all three water loss mechanisms occur concurrently.

  17. Going clean: structure and dynamics of peptides in the gas phase and paths to solvation

    NASA Astrophysics Data System (ADS)

    Baldauf, Carsten; Rossi, Mariana

    2015-12-01

    The gas phase is an artificial environment for biomolecules that has gained much attention both experimentally and theoretically due to its unique characteristic of providing a clean room environment for the comparison between theory and experiment. In this review we give an overview mainly on first-principles simulations of isolated peptides and the initial steps of their interactions with ions and solvent molecules: a bottom up approach to the complexity of biological environments. We focus on the accuracy of different methods to explore the conformational space, the connections between theory and experiment regarding collision cross section evaluations and (anharmonic) vibrational spectra, and the challenges faced in this field.

  18. Effects of metal ion adduction on the gas-phase conformations of protein ions.

    PubMed

    Flick, Tawnya G; Merenbloom, Samuel I; Williams, Evan R

    2013-11-01

    Changes in protein ion conformation as a result of nonspecific adduction of metal ions to the protein during electrospray ionization (ESI) from aqueous solutions were investigated using traveling wave ion mobility spectrometry (TWIMS). For all proteins examined, protein cations (and in most cases anions) with nonspecific metal ion adducts are more compact than the fully protonated (or deprotonated) ions with the same charge state. Compaction of protein cations upon nonspecific metal ion binding is most significant for intermediate charge state ions, and there is a greater reduction in collisional cross section with increasing number of metal ion adducts and increasing ion valency, consistent with an electrostatic interaction between the ions and the protein. Protein cations with the greatest number of adducted metal ions are no more compact than the lowest protonated ions formed from aqueous solutions. These results show that smaller collisional cross sections for metal-attached protein ions are not a good indicator of a specific metal-protein interaction in solution because nonspecific metal ion adduction also results in smaller gaseous protein cation cross sections. In contrast, the collisional cross section of α-lactalbumin, which specifically binds one Ca(2+), is larger for the holo-form compared with the apo-form, in agreement with solution-phase measurements. Because compaction of protein cations occurs when metal ion adduction is nonspecific, elongation of a protein cation may be a more reliable indicator that a specific metal ion-protein interaction occurs in solution.

  19. Effects of Metal Ion Adduction on the Gas-Phase Conformations of Protein Ions

    PubMed Central

    Flick, Tawnya G.; Merenbloom, Samuel I.; Williams, Evan R.

    2013-01-01

    Changes in protein ion conformation as a result of nonspecific adduction of metal ions to the protein during electrospray ionization (ESI) from aqueous solutions were investigated using traveling wave ion mobility spectrometry (TWIMS). For all proteins examined, protein cations (and in most cases anions) with nonspecific metal ion adducts are more compact than the fully protonated (or deprotonated) ions with the same charge state. Compaction of protein cations upon nonspecific metal ion binding is most significant for intermediate charge state ions, and there is a greater reduction in collisional cross section with increasing number of metal ion adducts and increasing ion valency, consistent with an electrostatic interaction between the ions and the protein. Protein cations with the greatest number of adducted metal ions are no more compact than the lowest protonated ions formed from aqueous solutions. These results show that smaller collisional cross sections for metal-attached protein ions are not a good indicator of a specific metal-protein interaction in solution, because nonspecific metal ion adduction also results in smaller gaseous protein cation cross sections. In contrast, the collisional cross section of α-lactalbumin, which specifically binds one Ca2+, is larger for the holo-form compared to the apo-form, in agreement with solution-phase measurements. Because compaction of protein cations occurs when metal ion adduction is nonspecific, elongation of a protein cation may be a more reliable indicator that a specific metal ion-protein interaction occurs in solution. PMID:23733259

  20. Gas-phase structure and reactivity of the keto tautomer of the deoxyguanosine radical cation.

    PubMed

    Feketeová, Linda; Chan, Bun; Khairallah, George N; Steinmetz, Vincent; Maître, Philippe; Radom, Leo; O'Hair, Richard A J

    2015-10-21

    Guanine radical cations are formed upon oxidation of DNA. Deoxyguanosine (dG) is used as a model, and the gas-phase infrared (IR) spectroscopic signature and gas-phase unimolecular and bimolecular chemistry of its radical cation, dG˙(+), A, which is formed via direct electrospray ionisation (ESI/MS) of a methanolic solution of Cu(NO3)2 and dG, are examined. Quantum chemistry calculations have been carried out on 28 isomers and comparisons between their calculated IR spectra and the experimentally-measured spectra suggest that A exists as the ground-state keto tautomer. Collision-induced dissociation (CID) of A proceeds via cleavage of the glycosidic bond, while its ion–molecule reactions with amine bases occur via a number of pathways including hydrogen-atom abstraction, proton transfer and adduct formation. A hidden channel, involving isomerisation of the radical cation via adduct formation, is revealed through the use of two stages of CID, with the final stage of CID showing the loss of CH2O as a major fragmentation pathway from the reformed radical cation, dG˙(+). Quantum chemistry calculations on the unimolecular and bimolecular reactivity are also consistent with A being present as a ground-state keto tautomer. PMID:25942055

  1. Development of a Polarizable Force Field For Proteins via Ab Initio Quantum Chemistry: First Generation Model and Gas Phase Tests

    PubMed Central

    KAMINSKI, GEORGE A.; STERN, HARRY A.; BERNE, B. J.; FRIESNER, RICHARD A.; CAO, YIXIANG X.; MURPHY, ROBERT B.; ZHOU, RUHONG; HALGREN, THOMAS A.

    2014-01-01

    We present results of developing a methodology suitable for producing molecular mechanics force fields with explicit treatment of electrostatic polarization for proteins and other molecular system of biological interest. The technique allows simulation of realistic-size systems. Employing high-level ab initio data as a target for fitting allows us to avoid the problem of the lack of detailed experimental data. Using the fast and reliable quantum mechanical methods supplies robust fitting data for the resulting parameter sets. As a result, gas-phase many-body effects for dipeptides are captured within the average RMSD of 0.22 kcal/mol from their ab initio values, and conformational energies for the di- and tetrapeptides are reproduced within the average RMSD of 0.43 kcal/mol from their quantum mechanical counterparts. The latter is achieved in part because of application of a novel torsional fitting technique recently developed in our group, which has already been used to greatly improve accuracy of the peptide conformational equilibrium prediction with the OPLS-AA force field.1 Finally, we have employed the newly developed first-generation model in computing gas-phase conformations of real proteins, as well as in molecular dynamics studies of the systems. The results show that, although the overall accuracy is no better than what can be achieved with a fixed-charges model, the methodology produces robust results, permits reasonably low computational cost, and avoids other computational problems typical for polarizable force fields. It can be considered as a solid basis for building a more accurate and complete second-generation model. PMID:12395421

  2. Simple setup for gas-phase H/D exchange mass spectrometry coupled to electron transfer dissociation and ion mobility for analysis of polypeptide structure on a liquid chromatographic time scale.

    PubMed

    Mistarz, Ulrik H; Brown, Jeffery M; Haselmann, Kim F; Rand, Kasper D

    2014-12-01

    Gas-phase hydrogen/deuterium exchange (HDX) is a fast and sensitive, yet unharnessed analytical approach for providing information on the structural properties of biomolecules, in a complementary manner to mass analysis. Here, we describe a simple setup for ND3-mediated millisecond gas-phase HDX inside a mass spectrometer immediately after ESI (gas-phase HDX-MS) and show utility for studying the primary and higher-order structure of peptides and proteins. HDX was achieved by passing N2-gas through a container filled with aqueous deuterated ammonia reagent (ND3/D2O) and admitting the saturated gas immediately upstream or downstream of the primary skimmer cone. The approach was implemented on three commercially available mass spectrometers and required no or minor fully reversible reconfiguration of gas-inlets of the ion source. Results from gas-phase HDX-MS of peptides using the aqueous ND3/D2O as HDX reagent indicate that labeling is facilitated exclusively through gaseous ND3, yielding similar results to the infusion of purified ND3-gas, while circumventing the complications associated with the use of hazardous purified gases. Comparison of the solution-phase- and gas-phase deuterium uptake of Leu-Enkephalin and Glu-Fibrinopeptide B, confirmed that this gas-phase HDX-MS approach allows for labeling of sites (heteroatom-bound non-amide hydrogens located on side-chains, N-terminus and C-terminus) not accessed by classical solution-phase HDX-MS. The simple setup is compatible with liquid chromatography and a chip-based automated nanoESI interface, allowing for online gas-phase HDX-MS analysis of peptides and proteins separated on a liquid chromatographic time scale at increased throughput. Furthermore, online gas-phase HDX-MS could be performed in tandem with ion mobility separation or electron transfer dissociation, thus enabling multiple orthogonal analyses of the structural properties of peptides and proteins in a single automated LC-MS workflow.

  3. Fluorine Bonding Enhances the Energetics of Protein-Lipid Binding in the Gas Phase

    NASA Astrophysics Data System (ADS)

    Liu, Lan; Jalili, Nobar; Baergen, Alyson; Ng, Simon; Bailey, Justin; Derda, Ratmir; Klassen, John S.

    2014-05-01

    This paper reports on the first experimental study of the energies of noncovalent fluorine bonding in a protein-ligand complex in the absence of solvent. Arrhenius parameters were measured for the dissociation of gaseous deprotonated ions of complexes of bovine β-lactoglobulin (Lg), a model lipid-binding protein, and four fluorinated analogs of stearic acid (SA), which contained (X =) 13, 15, 17, or 21 fluorine atoms. In all cases, the activation energies (Ea) measured for the loss of neutral XF-SA from the (Lg + XF-SA)7- ions are larger than for SA. From the kinetic data, the average contribution of each > CF2 group to Ea was found to be ~1.1 kcal mol-1, which is larger than the ~0.8 kcal mol-1 value reported for > CH2 groups. Based on these results, it is proposed that fluorocarbon-protein interactions are inherently stronger (enthalpically) than the corresponding hydrocarbon interactions.

  4. Conformational analysis of green apple flavour: the gas-phase structure of ethyl valerate validated by microwave spectroscopy.

    PubMed

    Mouhib, H; Stahl, W

    2012-04-10

    We report on the microwave spectrum of ethyl valerate, C(4)H(9)-COO-C(2)H(5), observed by molecular beam Fourier transform microwave spectroscopy (MB-FTMW). Highly accurate rotational and centrifugal distortion constants of the two most abundant conformers were determined. Their structure was investigated by comparison of the experimental rotational constants with those obtained by quantum chemical calculations. MP2/ 6-311++G(d,p) calculations failed to give a proper description of the observed conformers in the supersonic jet. Therefore, also other basis sets were tried using Hartree-Fock, second-order Møller-Plesset (MP2), and B3LYP methods to predict the observed gas-phase structures of the molecule. The quantum chemical results guided the conformer assignment of the rotational constants, obtained from the microwave experiment. One of the two observed conformers has C(s) symmetry, while the most abundant conformer has C(1) symmetry. The main conformer possesses a strong spectrum with high intensities. Additionally, harmonic frequency calculations at different levels of theory where carried out and a low lying vibration of the entire n-butyl group against the rest of the molecule was identified. The symbiotic interplay of microwave gas-phase investigations and quantum chemical calculations becomes evident in our results.

  5. The singular gas-phase structure of 1-aminocyclopropanecarboxylic acid (Ac3c).

    PubMed

    Jiménez, Ana I; Vaquero, Vanesa; Cabezas, Carlos; López, Juan C; Cativiela, Carlos; Alonso, José L

    2011-07-13

    The natural nonproteinogenic α-amino acid 1-aminocyclopropanecarboxylic acid (Ac(3)c) has been vaporized by laser ablation and studied in the gas phase by molecular-beam Fourier transform microwave spectroscopy. Comparison of the experimental rotational and (14)N nuclear quadrupole coupling constants with the values predicted ab initio for these parameters has allowed the unambiguous identification of three Ac(3)c conformers differing in the hydrogen bonding pattern. Two of them resemble those characterized before for the coded aliphatic α-amino acids. Remarkably, a third conformer predicted to be energetically accessible for all of these amino acids but never observed (the so-called "missing conformer") has been found for Ac(3)c, close in energy to the global minimum. This is the first time that such a conformer, stabilized by an N-H···O(H) hydrogen bond, is detected in the rotational spectrum of a gaseous α-amino acid with a nonpolar side chain. The conjugative interaction established between the cyclopropane ring and the adjacent carbonyl group seems to be responsible for the unique conformational properties exhibited by Ac(3)c.

  6. Analyte induced water adsorbability in gas phase biosensors: the influence of ethinylestradiol on the water binding protein capacity.

    PubMed

    Snopok, Borys; Kruglenko, Ivanna

    2015-05-01

    An ultra-sensitive gas phase biosensor/tracer/bio-sniffer is an emerging technology platform designed to provide real-time information on air-borne analytes, or those in liquids, through classical headspace analysis. The desired bio-sniffer measures gaseous 17α- ethinylestradiol (ETED) as frequency changes on a quartz crystal microbalance (QCM), which is a result of the interactions of liquid sample components in the headspace (ETED and water) with a biorecognition layer. The latter was constructed by immobilization of polyclonal antiserum against a phenolic A-ring of estrogenic receptors through protein A. The QCM response exhibited stretched exponential kinetics of negative frequency shifts with reversible and "irreversible" components of mass uptake onto the sensor surface in static headspace conditions when exposed to water solutions of ETED over the sensor working range, from 10(-10) to 10(-17) g L(-1). It was shown that the variations in the QCM response characteristics are due to the change of the water-binding capacity of the sensing layer induced by protein transformations initiated by the binding of ETED molecules. This result is well correlated with the natural physiological function of estrogens in controlling the homeostasis of body fluids in living beings. PMID:25763411

  7. Proton transfer from the inactive gas-phase nicotine structure to the bioactive aqueous-phase structure.

    PubMed

    Gaigeot, Marie-Pierre; Cimas, Alvaro; Seydou, Mahamadou; Kim, Ju-Young; Lee, Sungyul; Schermann, Jean-Pierre

    2010-12-29

    The role of water in the structural change of nicotine from its inactive form in the gas phase to its bioactive form in aqueous solution has been investigated by two complementary theoretical approaches, i.e., geometry optimizations and molecular dynamics. Structures of the lowest-energy nicotineH(+)-(H(2)O)(n) complexes protonated either on the pyridine (inactive form) or pyrrolidine (active form) ring have been calculated, as well as the free-energy barriers for the proton-transfer tautomerization between the two cycles. These structures show chains of 2-4 water molecules bridging the two protonation sites. The room-temperature free-energy barrier to tautomerization along the minimum-energy path from the pyridine to the pyrrolidine cycle drops rapidly when the number of water molecules increases from 0 to 4, but still remains rather high (16 kJ/mol with four water molecules), indicating that the proton transfer is a rather difficult and rare event. We compare results obtained through this explicit water molecule approach to those obtained by means of continuum methods. Car-Parrinello molecular dynamics (CPMD) simulations of the proton-transfer process in bulk with explicit water molecules have been conducted at room temperature. No spontaneous proton transfers have been observed during the dynamics, and biased CPMD simulations have therefore been performed in order to measure the free-energy profile of the proton transfer in the aqueous phase and to reveal the proton-transfer mechanism through water bridges. The MD bias involves pulling the proton from the pyridine ring to the surrounding bulk. Dynamics show that this triggers the tautomerization toward the pyrrolidine ring, proceeding without energy barrier. The proton transfer is extremely fast, and protonation of the pyrrolidine ring was achieved within 0.5 ps. CPMD simulations confirmed the pivotal role played by the water molecules that bridge the two protonation sites of nicotine within the bulk of the

  8. The lineshape of the electronic spectrum of the green fluorescent protein chromophore, part I: gas phase.

    PubMed

    Davari, Mehdi D; Ferrer, Francisco J Avila; Morozov, Dmitry; Santoro, Fabrizio; Groenhof, Gerrit

    2014-10-20

    In this work we present the vibrationally resolved optical absorption spectrum of p-hydroxybenzylidene-2,3-dimethylimidazolinone (HBDI), the green fluorescent protein (GFP) chromophore, computed at several levels of theory, including time-dependent DFT with various functionals and basis sets, CASSCF, CASPT2 and XMCQDPT2. We also investigated what happens to the spectrum if the ground- and excited-state geometries are optimized at different levels of theory (mixed approach), as has been used previously. The vibrationally resolved absorption spectra obtained by DFT, CASPT2 and XMCQDPT2 are very similar and consist of a main absorption peak and a shoulder that is ∼1500 cm(-1) higher in energy. The vibrational progression increases moderately with temperature. These spectra are in qualitative agreement with experimental action spectra, but much narrower and lack the long tail in the blue, even at high temperatures. Because our calculated emission spectra, which are equally narrow, are in good agreement with the emission of green fluorescent protein at 253 K, we argue that the action spectrum are too broad to be considered as the absorption spectrum. The CASSCF method and the mixed approaches overestimate the vibrational progressions with respect to CAM-B3LYP, CASPT2 and XMCQDPT2, due to inaccuracies in the geometric S0 →S1 displacements. Finally, we computed the vibronic spectra of four chromophore analogues with different substitutions on the rings and found that these substitutions hardly affect the lineshape in vacuum.

  9. Microwave spectra and gas phase structural parameters for N-hydroxypyridine-2(1H)-thione.

    PubMed

    Daly, Adam M; Mitchell, Erik G; Sanchez, Daniel A; Block, Eric; Kukolich, Stephen G

    2011-12-22

    The microwave spectrum for N-hydroxypyridine-2(1H)-thione (pyrithione) was measured in the frequency range 6-18 GHz, providing accurate rotational constants and nitrogen quadrupole coupling strengths for three isotopologues, C(5)H(4)(32)S(14)NOH, C(5)H(4)(32)S(14)NOD, and C(5)H(4)(34)S(14)NOH. Pyrithione was found to be in a higher concentration in the gas phase than the other tautomer, 2-mercaptopyridine-N-oxide (MPO). Microwave spectroscopy is best suited to determine which structure predominates in the gas phase. The measured rotational constants were used to accurately determine the coordinates of the substituted atoms and provided sufficient data to determine some of the important structural parameters for pyrithione, the only tautomer observed in the present work. The spectra were obtained using a pulsed-beam Fourier transform microwave spectrometer, with sufficient resolution to allow accurate measurements of the (14)N nuclear quadrupole hyperfine interactions. Ab initio calculations provided structural parameters and quadrupole coupling strengths that are in very good agreement with measured values. The experimental rotational constants for the parent compound are A = 3212.10(1), B = 1609.328(7), and C = 1072.208(6) MHz, yielding the inertial defect Δ(0) = -0.023 amu·Å(2) for the C(5)H(4)(32)S(14)NOH isotopologue. The observed near zero inertial defect clearly indicates a planar structure. The least-squares fit structural analysis yielded the experimental bond lengths R(O-H) = 0.93(2) Å, R(C-S) = 1.66(2) Å, and angle (N-O-H) = 105(4)° for the ground state structure.

  10. Microwave spectra and gas phase structural parameters for N-hydroxypyridine-2(1H)-thione.

    PubMed

    Daly, Adam M; Mitchell, Erik G; Sanchez, Daniel A; Block, Eric; Kukolich, Stephen G

    2011-12-22

    The microwave spectrum for N-hydroxypyridine-2(1H)-thione (pyrithione) was measured in the frequency range 6-18 GHz, providing accurate rotational constants and nitrogen quadrupole coupling strengths for three isotopologues, C(5)H(4)(32)S(14)NOH, C(5)H(4)(32)S(14)NOD, and C(5)H(4)(34)S(14)NOH. Pyrithione was found to be in a higher concentration in the gas phase than the other tautomer, 2-mercaptopyridine-N-oxide (MPO). Microwave spectroscopy is best suited to determine which structure predominates in the gas phase. The measured rotational constants were used to accurately determine the coordinates of the substituted atoms and provided sufficient data to determine some of the important structural parameters for pyrithione, the only tautomer observed in the present work. The spectra were obtained using a pulsed-beam Fourier transform microwave spectrometer, with sufficient resolution to allow accurate measurements of the (14)N nuclear quadrupole hyperfine interactions. Ab initio calculations provided structural parameters and quadrupole coupling strengths that are in very good agreement with measured values. The experimental rotational constants for the parent compound are A = 3212.10(1), B = 1609.328(7), and C = 1072.208(6) MHz, yielding the inertial defect Δ(0) = -0.023 amu·Å(2) for the C(5)H(4)(32)S(14)NOH isotopologue. The observed near zero inertial defect clearly indicates a planar structure. The least-squares fit structural analysis yielded the experimental bond lengths R(O-H) = 0.93(2) Å, R(C-S) = 1.66(2) Å, and angle (N-O-H) = 105(4)° for the ground state structure. PMID:22070758

  11. Experimental observation of the transition between gas-phase and aqueous solution structures for acetylcholine, nicotine, and muscarine ions.

    PubMed

    Seydou, Mahamadou; Grégoire, Gilles; Liquier, Jean; Lemaire, J; Schermann, Jean Pierre; Desfrançois, Charles

    2008-03-26

    Structural information on acetylcholine and its two agonists, nicotine, and muscarine has been obtained from the interpretation of infrared spectra recorded in the gas-phase or in low pH aqueous solutions. Simulated IR spectra have been obtained using explicit water molecules or a polarization continuum model. The conformational space of the very flexible acetylcholine ions is modified by the presence of the solvent. Distances between its pharmacophoric groups cover a lower range in hydrated species than in isolated species. A clear signature of the shift of protonation site in nicotine ions is provided by the striking change of their infrared spectrum induced by hydration. On the contrary, structures of muscarine ions are only slightly influenced by the presence of water.

  12. Gas phase studies of the Pesci decarboxylation reaction: synthesis, structure, and unimolecular and bimolecular reactivity of organometallic ions.

    PubMed

    O'Hair, Richard A J; Rijs, Nicole J

    2015-02-17

    CONSPECTUS: Decarboxylation chemistry has a rich history, and in more recent times, it has been recruited in the quest to develop cheaper, cleaner, and more efficient bond-coupling reactions. Thus, over the past two decades, there has been intense investigation into new metal-catalyzed reactions of carboxylic substrates. Understanding the elementary steps of metal-mediated transformations is at the heart of inventing new reactions and improving the performance of existing ones. Fortunately, during the same time period, there has been a convergence in mass spectrometry (MS) techniques, which allows these catalytic processes to be examined efficiently in the gas phase. Thus, electrospray ionization (ESI) sources have been combined with ion-trap mass spectrometers, which in turn have been modified to either accept radiation from tunable OPO lasers for spectroscopy based structural assignment of ions or to allow the study of ion-molecule reactions (IMR). The resultant "complete" gas-phase chemical laboratories provide a platform to study the elementary steps of metal-catalyzed decarboxylation reactions in exquisite detail. In this Account, we illustrate how the powerful combination of ion trap mass spectrometry experiments and DFT calculations can be systematically used to examine the formation of organometallic ions and their chemical transformations. Specifically, ESI-MS allows the transfer of inorganic carboxylate complexes, [RCO2M(L)n](x), (x = charge) from the condensed to the gas phase. These mass selected ions serve as precursors to organometallic ions [RM(L)n](x) via neutral extrusion of CO2, accessible by slow heating in the ion trap using collision induced dissociation (CID). This approach provides access to an array of organometallic ions with well-defined stoichiometry. In terms of understanding the decarboxylation process, we highlight the role of the metal center (M), the organic group (R), and the auxiliary ligand (L), along with cluster nuclearity, in

  13. Gas phase studies of the Pesci decarboxylation reaction: synthesis, structure, and unimolecular and bimolecular reactivity of organometallic ions.

    PubMed

    O'Hair, Richard A J; Rijs, Nicole J

    2015-02-17

    CONSPECTUS: Decarboxylation chemistry has a rich history, and in more recent times, it has been recruited in the quest to develop cheaper, cleaner, and more efficient bond-coupling reactions. Thus, over the past two decades, there has been intense investigation into new metal-catalyzed reactions of carboxylic substrates. Understanding the elementary steps of metal-mediated transformations is at the heart of inventing new reactions and improving the performance of existing ones. Fortunately, during the same time period, there has been a convergence in mass spectrometry (MS) techniques, which allows these catalytic processes to be examined efficiently in the gas phase. Thus, electrospray ionization (ESI) sources have been combined with ion-trap mass spectrometers, which in turn have been modified to either accept radiation from tunable OPO lasers for spectroscopy based structural assignment of ions or to allow the study of ion-molecule reactions (IMR). The resultant "complete" gas-phase chemical laboratories provide a platform to study the elementary steps of metal-catalyzed decarboxylation reactions in exquisite detail. In this Account, we illustrate how the powerful combination of ion trap mass spectrometry experiments and DFT calculations can be systematically used to examine the formation of organometallic ions and their chemical transformations. Specifically, ESI-MS allows the transfer of inorganic carboxylate complexes, [RCO2M(L)n](x), (x = charge) from the condensed to the gas phase. These mass selected ions serve as precursors to organometallic ions [RM(L)n](x) via neutral extrusion of CO2, accessible by slow heating in the ion trap using collision induced dissociation (CID). This approach provides access to an array of organometallic ions with well-defined stoichiometry. In terms of understanding the decarboxylation process, we highlight the role of the metal center (M), the organic group (R), and the auxiliary ligand (L), along with cluster nuclearity, in

  14. Gas phase IR spectra of tri-peptide Z-Pro-Leu-Gly: Effect of C-terminal amide capping on secondary structure

    NASA Astrophysics Data System (ADS)

    Chakraborty, Shamik; Yamada, Kohei; Ishiuchi, Shun-ichi; Fujii, Masaaki

    2012-04-01

    Three-residue peptides capped with benzyloxycarbonyl (Z-) group, Z-Pro-Leu-Gly-NH2 and Z-Pro-Leu-Gly-OH, are investigated by infrared (IR) spectroscopy, using supersonic-jet laser desorption technique, in the N-H and O-H stretching frequency ranges. The IR spectra show clear evidence of the formation of different hydrogen-bonding network in the two peptides. The possible gas phase structure is proposed from density functional theory calculations using cc-pVDZ basis set. The Z-Pro-Leu-Gly-OH in the gas phase forms successive γ-turn structure with free C-terminal carboxyl group whereas main structural element in Z-Pro-Leu-Gly-NH2 is β-turn with C-terminal sbnd NH2 group forming hydrogen bond. Structural information is employed to predict their binding capability in gas phase.

  15. An experimental and computational investigation into the gas-phase acidities of tyrosine and phenylalanine: three structures for deprotonated tyrosine.

    PubMed

    Bokatzian, Samantha S; Stover, Michele L; Plummer, Chelsea E; Dixon, David A; Cassady, Carolyn J

    2014-11-01

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

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

    SciTech Connect

    Bokatzian, Samantha S.; Stover, Michele L.; Plummer, Chelsea E.; Dixon, David A.; Cassady, Carolyn J.

    2014-11-06

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

  17. An experimental and computational investigation into the gas-phase acidities of tyrosine and phenylalanine: three structures for deprotonated tyrosine.

    PubMed

    Bokatzian, Samantha S; Stover, Michele L; Plummer, Chelsea E; Dixon, David A; Cassady, Carolyn J

    2014-11-01

    Using mass spectrometry and correlated molecular orbital theory, three deprotonated structures were revealed for the amino acid tyrosine. The structures were distinguished experimentally by ion/molecule reactions involving proton transfer and trimethylsilyl azide. Gas-phase acidities from proton transfer reactions and from G3(MP2) calculations generally agree well. The lowest energy structure, which was only observed experimentally using electrospray ionization from aprotic solvents, is deprotonated at the carboxylic acid group and is predicted to be highly folded. A second unfolded carboxylate structure is several kcal/mol higher in energy and primarily forms from protic solvents. Protic solvents also yield a structure deprotonated at the phenolic side chain, which experiments find to be intermediate in energy to the two carboxylate forms. G3(MP2) calculations indicate that the three structures differ in energy by only 2.5 kcal/mol, yet they are readily distinguished experimentally. Structural abundance ratios are dependent upon experimental conditions, including the solvent and accumulation time of ions in a hexapole. Under some conditions, carboxylate ions may convert to phenolate ions. For phenylalanine, which lacks a phenolic group, only one deprotonated structure was observed experimentally when electrosprayed from protic solvent. This agrees with G3(MP2) calculations that find the folded and unfolded carboxylate forms to differ by 0.3 kcal/mol. PMID:25299802

  18. Unravelling the impact of hydrocarbon structure on the fumarate addition mechanism--a gas-phase ab initio study.

    PubMed

    Bharadwaj, Vivek S; Vyas, Shubham; Villano, Stephanie M; Maupin, C Mark; Dean, Anthony M

    2015-02-14

    The fumarate addition reaction mechanism is central to the anaerobic biodegradation pathway of various hydrocarbons, both aromatic (e.g., toluene, ethyl benzene) and aliphatic (e.g., n-hexane, dodecane). Succinate synthase enzymes, which belong to the glycyl radical enzyme family, are the main facilitators of these biochemical reactions. The overall catalytic mechanism that converts hydrocarbons to a succinate molecule involves three steps: (1) initial H-abstraction from the hydrocarbon by the radical enzyme, (2) addition of the resulting hydrocarbon radical to fumarate, and (3) hydrogen abstraction by the addition product to regenerate the radical enzyme. Since the biodegradation of hydrocarbon fuels via the fumarate addition mechanism is linked to bio-corrosion, an improved understanding of this reaction is imperative to our efforts of predicting the susceptibility of proposed alternative fuels to biodegradation. An improved understanding of the fuel biodegradation process also has the potential to benefit bioremediation. In this study, we consider model aromatic (toluene) and aliphatic (butane) compounds to evaluate the impact of hydrocarbon structure on the energetics and kinetics of the fumarate addition mechanism by means of high level ab initio gas-phase calculations. We predict that the rate of toluene degradation is ∼100 times faster than butane at 298 K, and that the first abstraction step is kinetically significant for both hydrocarbons, which is consistent with deuterium isotope effect studies on toluene degradation. The detailed computations also show that the predicted stereo-chemical preference of the succinate products for both toluene and butane are due to the differences in the radical addition rate constants for the various isomers. The computational and kinetic modeling work presented here demonstrates the importance of considering pre-reaction and product complexes in order to accurately treat gas phase systems that involve intra and inter

  19. Structure of Protonated Threonine Dimers in the Gas Phase: Salt-Bridged or Charge-Solvated?

    NASA Astrophysics Data System (ADS)

    Yin, Hong; Kong, Xianglei

    2015-09-01

    For homodimers of amino acids, their salt-bridged structures are gradually stabilized as the proton affinity of the component amino acid increases. Threonine has a proton affinity value located in the middle of the list of 20 natural amino acids. Thus, identifying whether the most stable isomer of protonated threonine dimer (Thr2H+) has a charge-solvated or salt-bridged structure is important and helpful for understanding the structures of other homodimers. By combining infrared photodissociation (IRPD) spectroscopy and theoretical calculations, the structures of Thr2H+ were investigated. Based on calculations at the M062X/6-311++G(d,p)//M062X/6-311++G(d,p) level, the most stable isomer of Thr2H+ was computed to be a charge-solvated structure, with an energy 3.87 kcal/mol lower than the most stable salt-bridged isomer. The predicted infrared spectrum is in good agreement with the experimental spectrum. To evaluate the temperature effect on the distribution of different isomers, the relative concentrations of the six isomers of Thr2H+ were calculated at different temperatures, according to their partition functions and enthalpies. The results show that the isomers are dominated by charge-solvated structures at a temperature of 300 K.

  20. Probing the electronic properties and structural evolution of anionic gold clusters in the gas phase

    NASA Astrophysics Data System (ADS)

    Wang, Lei-Ming; Wang, Lai-Sheng

    2012-06-01

    Gold nanoparticles have been discovered to exhibit remarkable catalytic properties in contrast to the chemical inertness of bulk gold. A prerequisite to elucidate the molecular mechanisms of the catalytic effect of nanogold is a detailed understanding of the structural and electronic properties of gold clusters as a function of size. In this review, we describe joint experimental studies (mainly photoelectron spectroscopy) and theoretical calculations to probe the structural properties of anionic gold clusters. Electronic properties and structural evolutions of all known Aun- clusters as experimentally confirmed to date are summarized, covering the size ranges of n = 3-35 and 55-64. Recent experimental efforts in resolving the isomeric issues of small gold clusters using Ar-tagging, O2-titration and isoelectronic substitution are also discussed.

  1. Probing the structures of gas-phase rhodium cluster cations by far-infrared spectroscopy

    SciTech Connect

    Harding, D. J.; Gruene, P.; Haertelt, M.; Meijer, G.; Fielicke, A.; Hamilton, S. M.; Hopkins, W. S.; Mackenzie, S. R.; Neville, S. P.; Walsh, T. R.

    2010-12-07

    The geometric structures of small cationic rhodium clusters Rh{sub n}{sup +} (n = 6-12) are investigated by comparison of experimental far-infrared multiple photon dissociation spectra with spectra calculated using density functional theory. The clusters are found to favor structures based on octahedral and tetrahedral motifs for most of the sizes considered, in contrast to previous theoretical predictions that rhodium clusters should favor cubic motifs. Our findings highlight the need for further development of theoretical and computational methods to treat these high-spin transition metal clusters.

  2. Gas-Phase Structures of Linalool and Coumarin Studied by Microwave Spectroscopy

    NASA Astrophysics Data System (ADS)

    Nguyen, H. V. L.; Stahl, W.; Grabow, J.-U.

    2013-06-01

    The microwave spectra of two natural substances, linalool and coumarin, were recorded in the microwave range from 9 to 16 GHz and 8.5 to 10.5 GHz, respectively.Linalool is an acyclic monoterpene and the main component of lavender oil. It has a structure with many possible conformations. The geometry of the lowest energy conformer has been determined by a combination of microwave spectroscopy and quantum chemical calculations. Surprisingly, a globular rather than a prolate shape was found. This structure is probably stabilized by a π interaction between two double bonds which are arranged in two stacked layers of atoms within the molecule. A-E splittings due to the internal rotation of one methyl group could be resolved and the barrier to internal rotation was determined to be 400.20(64) cm^{-1}. The standard deviation of the fit was close to experimental accuracy. For an identification of the observed conformer not only the rotational constants but also the internal rotation parameters of one of the methyl groups were needed. Coumarin is a widely used flavor in perfumery as sweet woodruff scent. The aromatic structure allows solely for one planar conformer, which was found under molecular beam conditions and compared to other molecules with similar structures. Here, the rotational spectrum could be described by a set of parameters including the rotational constants and the centrifugal distortion constants using a semi-rigid molecule Hamiltonian. Furthermore, the rotational transitions of all nine ^{13}C isotopologues were measured in natural abundance. As a consequence, the microwave structure of coumarin could be almost completely determined.

  3. Gas-phase synthesis and structure of monomeric ZnOH: a model species for metalloenzymes and catalytic surfaces.

    PubMed

    Zack, Lindsay N; Sun, Ming; Bucchino, Matthew P; Clouthier, Dennis J; Ziurys, Lucy M

    2012-02-16

    Monomeric ZnOH has been studied for the first time using millimeter and microwave gas-phase spectroscopy. ZnOH is important in surface processes and at the active site of the enzyme carbonic anhydrase. In the millimeter-wave direct-absorption experiments, ZnOH was synthesized by reacting zinc vapor, produced in a Broida-type oven, with water. In the Fourier-transform microwave measurements, ZnOH was produced in a supersonic jet expansion of CH(3)OH and zinc vapor, created by laser ablation. Multiple rotational transitions of six ZnOH isotopologues in their X(2)A' ground states were measured over the frequency range of 22-482 GHz, and splittings due to fine and hyperfine structure were resolved. An asymmetric top pattern was observed in the spectra, showing that ZnOH is bent, indicative of covalent bonding. From these data, spectroscopic constants and an accurate structure were determined. The Zn-O bond length was found to be similar to that in carbonic anhydrase and other model enzyme systems.

  4. Investigation of the gas-phase structure and rotational barrier of trimethylsilyl trifluoromethanesulfonate and comparison with covalent sulfonates

    NASA Astrophysics Data System (ADS)

    Defonsi Lestard, María E.; Tuttolomondo, María E.; Varetti, Eduardo L.; Wann, Derek A.; Robertson, Heather E.; Rankin, David W. H.; Altabef, Aida Ben

    2010-12-01

    The molecular structure of trimethylsilyl trifluoromethanesulfonate, CF 3SO 2OSi(CH 3) 3, has been determined in the gas phase from electron-diffraction data supplemented by ab initio (MP2) and DFT calculations using 6-31G(d), 6-311++G(d,p) and 6-311G++(3df,3pd) basis sets. Both experimental and theoretical data indicate that only one gauche conformer is possible by rotating about the O-S bond. The anomeric effect is a fundamental stereoelectronic interaction and presents a profound influence on the electronic geometry. We have investigated the origin of the anomeric effect by means of NBO and AIM analysis. A natural bond orbital analysis showed that the lpπ[O bonded to Si)] → σ *[C-S] hyperconjugative interaction favors the gauche conformation. In addition, comparison of the structural and stereoelectronic properties of the title molecule with those of silyl trifluoromethanesulfonate and methyl trifluoromethanesulfonate has been carried out.

  5. Conformational Transformation of Five-Membered Rings: the Gas Phase Structure of 2-METHYLTETRAHYDROFURAN

    NASA Astrophysics Data System (ADS)

    Van, Vinh; Nguyen, Ha Vinh Lam; Stahl, Wolfgang

    2015-06-01

    2-Methyltetrahydrofuran (2-MeTHF) is a promising environmentally friendly solvent and biofuel component which is derived from renewable resources. Following the principles of Green Chemistry, 2-MeTHF has been evaluated in various fields like organometallics, metathesis, and biosynthesis on the way to more eco-friendly syntheses. Cyclopentane as the prototype of five-membered rings is well-known to exist as twist or envelope structures. However, the conformational analysis of its heterocyclic derivative 2-methyl-tetrahydrothiophene (MTTP) yielded two stable twist conformers and two envelope transition states. Here, we report on the heavy atom r_s structure of the oxygen-analog of MTTP, 2-MeTHF, studied by a combination of molecular beam Fourier transform microwave spectroscopy and quantum chemistry. One conformer of 2-MeTHF was observed and highly accurate molecular parameters were determined using the XIAM program. In addition, all 13C-isotopologues were assigned in natural abundance of 1%. A structural determination based on the r_s positions of all carbon atoms was achieved via Kraitchman's equations. The methyl group in 2-MeTHF undergoes internal rotation and causes A-E splittings of the rotational lines. The barrier was calculated to be 1142 wn at the MP2/6-311++G(d,p) level of theory, which is rather high. Accordingly, narrow A-E splittings could be observed for only a few transitions. However, the barrier height could be fitted while the angles between the internal rotor axis and the principal axes of inertia were taken from the experimental geometry. V. Pace, P. Hoyos, L. Castoldi, P. Domínguez de María, A. R. Alcántara, ChemSusChem 5 (2012), 1369-1379. a) D. F. Aycock, Org. Process Res. Dev. 11 (2007),156-159. b) M. Smoleń, M. Kȩdziorek, K. Grela, Catal. Commun. 44 (2014), 80-84. V. Van, C. Dindic, H.V.L. Nguyen, W. Stahl, ChemPhysChem 16 (2015), 291-294. H. Hartwig, H. Dreizler, Z. Naturforsch. A 51 (1996), 923-932. J. Kraitchman, Am. J. Phys. 21

  6. Structures and fragmentation of [Cu(uracil-H)(uracil)]+ in the gas phase.

    PubMed

    Ali, Osama Y; Fridgen, Travis D

    2012-02-01

    Complexes of copper (II) ions and uracil were studied using tandem mass spectrometry (Fourier transform ion cyclotron resonance, FTICR, mass spectrometry) including extensive isotopic labeling as well as theoretical calculations. Positive ion electrospray mass spectra of aqueous solutions of CuCl(2) and uracil show that the [Cu(Ura-H)(Ura)](+) ion is the most abundant ion even at low concentrations of uracil. Sustained off-resonance irradiation collision-induced dissociation (SORI-CID) experiments show that the lowest energy decomposition pathway for [Cu(Ura-H)(Ura)](+) , surprisingly, is not the loss of uracil, but the loss of HNCO followed by HCN as the most abundant secondary fragmentation product. MS(n) studies identified primary, secondary and tertiary fragmentation products. Extensive isotopic labeling studies, as well as computational studies allowed for a detailed fragmentation scheme for the [Cu(Ura-H)(Ura)](+) ion, beginning with the lowest energy structure. PMID:22183913

  7. Structures and fragmentations of cobalt(II)-cysteine complexes in the gas phase.

    PubMed

    Buchmann, William; Spezia, Riccardo; Tournois, Guewen; Cartailler, Thierry; Tortajada, Jeanine

    2007-04-01

    The electronebulization of a cobalt(II)/cysteine(Cys) mixture in water/methanol (50/50) produced mainly cobalt-cationized species. Three main groups of the Co-cationized species can be distinguished in the ESI-MS spectrum: (1) the cobalt complexes including the cysteine amino acid only (they can be singly charged, for example, [Co(Cys)n- H]+ with n = 1-3 or doubly charged such as [Co + (Cys)2]2+); (2) the cobalt complexes with methanol: [Co(CH3OH)n- H]+ with n = 1-3, [Co(CH3OH)4]2+; and (3) the complexes with the two different types of ligands: [Co(Cys)(CH3OH) - H]+. Only the singly charged complexes were observed. Collision-induced dissociation (CID) products of the [Co(Cys)2]2+, [Co(Cys)2 - H]+ and [Co(Cys) - H]+ complexes were studied as a function of the collision energy, and mechanisms for the dissociation reactions are proposed. These were supported by the results of deuterium labelling experiments and by density functional theory calculations. Since [Co(Cys) - H]+ was one of the main product ions obtained upon the CID of [Co(Cys)2]2+ and of [Co(Cys)2 - H]+ under low-energy conditions, the fragmentation pathways of [Co(Cys) - H]+ and the resulting product ion structures were studied in detail. The resulting product ion structures confirmed the high affinity of cobalt(II) for the sulfur atom of cysteine. PMID:17323419

  8. Discriminating Properties of Alkali Metal Ions Towards the Constituents of Proteins and Nucleic Acids. Conclusions from Gas-Phase and Theoretical Studies.

    PubMed

    Rodgers, Mary T; Armentrout, Peter B

    2016-01-01

    Quantitative insight into the structures and thermodynamics of alkali metal cations interacting with biological molecules can be obtained from studies in the gas phase combined with theoretical work. In this chapter, the fundamentals of the experimental and theoretical techniques are first summarized and results for such work on complexes of alkali metal cations with amino acids, small peptides, and nucleobases are reviewed. Periodic trends in how these interactions vary as the alkali metal cations get heavier are highlighted.

  9. Gas phase chemistry in comets

    NASA Technical Reports Server (NTRS)

    Oppenheimer, M.

    1976-01-01

    The significance of gas phase reactions in determining the nuclear structure of comets is discussed. The sublimation of parent molecules such as H2O, CH4, CO2, and NH3 from the surface of the nucleus and their subsequent photodissociation and ionization in forming observed cometary molecular species are elaborated.

  10. Molecular structures of benzoic acid and 2-hydroxybenzoic acid, obtained by gas-phase electron diffraction and theoretical calculations.

    PubMed

    Aarset, Kirsten; Page, Elizabeth M; Rice, David A

    2006-07-20

    The structures of benzoic acid (C6H5COOH) and 2-hydroxybenzoic acid (C6H4OHCOOH) have been determined in the gas phase by electron diffraction using results from quantum chemical calculations to inform restraints used on the structural parameters. Theoretical methods (HF and MP2/6-311+G(d,p)) predict two conformers for benzoic acid, one which is 25.0 kJ mol(-1) (MP2) lower in energy than the other. In the low-energy form, the carboxyl group is coplanar with the phenyl ring and the O-H group eclipses the C=O bond. Theoretical calculations (HF and MP2/6-311+G(d,p)) carried out for 2-hydroxybenzoic acid gave evidence for seven stable conformers but one low-energy form (11.7 kJ mol(-1) lower in energy (MP2)) which again has the carboxyl group coplanar with the phenyl ring, the O-H of the carboxyl group eclipsing the C=O bond and the C=O of the carboxyl group oriented toward the O-H group of the phenyl ring. The effects of internal hydrogen bonding in 2-hydroxybenzoic acid can be clearly observed by comparison of pertinent structural parameters between the two compounds. These differences for 2-hydroxybenzoic acid include a shorter exocyclic C-C bond, a lengthening of the ring C-C bond between the substituents, and a shortening of the carboxylic single C-O bond. PMID:16836466

  11. Structures of protonated thymine and uracil and their monohydrated gas-phase ions from ultraviolet action spectroscopy and theory.

    PubMed

    Pedersen, Sara Øvad; Byskov, Camilla Skinnerup; Turecek, Frantisek; Brøndsted Nielsen, Steen

    2014-06-19

    The strong UV chromophores thymine (Thy) and uracil (Ura) have identical heteroaromatic rings that only differ by one methyl substituent. While their photophysics has been elucidated in detail, the effect on the excited states of base protonation and single water molecules is less explored. Here we report gas-phase absorption spectra of ThyH(+) and UraH(+) and monohydrated ions and demonstrate that the substituent is not only responsible for spectral shifts but also influences the tautomer distribution, being different for bare and monohydrated ions. Spectra interpretation is aided by calculations of geometrical structures and transition energies. The lowest free-energy tautomer (denoted 178, enol-enol form) accounts for 230-280 nm (ThyH(+)) and 225-270 nm (UraH(+)) bands. ThyH(+) hardly absorbs above 300 nm, whereas a discernible band is measured for UraH(+) (275-320 nm), ascribed to the second lowest free-energy tautomer (138, enol-keto form) comprising a few percent of the UraH(+) population at room temperature. Band widths are similar to those measured of cold ions in support of very short excited-state lifetimes. Attachment of a single water increases the abundance of 138 relative to 178, 138 now clearly present for ThyH(+). 138 resembles more the tautomer present in aqueous solution than 178 does, and 138 may indeed be a relevant transition structure. The band of ThyH(+)(178) is unchanged, that of UraH(+)(178) is nearly unchanged, and that of UraH(+)(138) blue-shifts by about 10 nm. In stark contrast to protonated adenine, more than one solvating water molecule is required to re-establish the absorption of ThyH(+) and UraH(+) in aqueous solution.

  12. Protein Structure

    ERIC Educational Resources Information Center

    Asmus, Elaine Garbarino

    2007-01-01

    Individual students model specific amino acids and then, through dehydration synthesis, a class of students models a protein. The students clearly learn amino acid structure, primary, secondary, tertiary, and quaternary structure in proteins and the nature of the bonds maintaining a protein's shape. This activity is fun, concrete, inexpensive and…

  13. Energetics and structural characterization of isomers using ion mobility and gas-phase H/D exchange: Learning from lasso peptides.

    PubMed

    Hanozin, Emeline; Morsa, Denis; De Pauw, Edwin

    2015-08-01

    State-of-the-art characterization of proteins using MS namely relies on fragmentation methods that allow exploring featured dissociative reaction pathways. These pathways are often initiated by a series of potentially informative mass-constant conformational changes that are nonetheless frequently overlooked by lack of adequate investigation techniques. In the present study, we propose a methodology to readily address both structural and energetic aspects of stereoisomerization reactions using ion mobility coupled with MS. To this end, a commercial spectrometer was used as a reactor comprising an energy resolved collisional activation step intended at promoting controlled conformational changes and a structural assignment step dedicated to the identification of the generated isomers. This identification relies on ion mobility and other on-line coupled techniques, namely an originally designed gas-phase H/D exchange experiment. We here apply this methodology to characterize the isomerization kinetics of capistruin, a 19-residue long lasso-folded peptide. We expect this approach to bring insights into the physical origin of global dissociation thresholds monitored in MS/MS experiments and to set a promising basis for quantitative investigations of the stability of different molecular folds.

  14. Gas Phase Nanoparticle Synthesis

    NASA Astrophysics Data System (ADS)

    Granqvist, Claes; Kish, Laszlo; Marlow, William

    This book deals with gas-phase nanoparticle synthesis and is intended for researchers and research students in nanomaterials science and engineering, condensed matter physics and chemistry, and aerosol science. Gas-phase nanoparticle synthesis is instrumental to nanotechnology - a field in current focus that raises hopes for environmentally benign, resource-lean manufacturing. Nanoparticles can be produced by many physical, chemical, and even biological routes. Gas-phase synthesis is particularly interesting since one can achieve accurate manufacturing control and hence industrial viability.

  15. Vibrational structure of n-π* transition of the UV absorption spectrum of acryloyl fluoride in the gas phase.

    PubMed

    Koroleva, Lidiya A; Tyulin, Vladimir I; Matveev, Vladimir K; Pentin, Yuriy A

    2014-03-25

    UV absorption spectrum of acryloyl fluoride molecule in the gas phase has been obtained in the region at 32600-35500 cm(-1) with the purpose of the investigation of the hindered internal rotation. The resolved vibrational structure of this spectrum consists of 92 absorption bands, each of which corresponds to a certain transition from the ground (S0) to excited (S1) electronic state. The assignment of all bands has been made. The values ν00trans=34831.8 cm(-1) and ν00cis=34679.2 cm(-1) have been determined. Several Deslandres Tables (DTs) have been constructed for torsional vibration of s-trans- and s-cis-isomers of investigated molecule. The origins in these DTs correspond to bands assigned to ν00 and to fundamental frequencies of each isomer in the S0 and S1 states. These DTs have been used to determine the harmonic frequencies ωe, anharmonicity coefficients x11, and frequencies of the torsional vibration transitions (0-υ) up to high values of the vibrational quantum number υ of s-trans- and s-cis-isomers in the both electronic states. The frequencies of torsional vibrations are ν1(″)=116.5cm(-1) for s-trans-isomer and ν1(″)=101.2 cm(-1) for s-cis-isomer in the S0 state. The frequencies of ones are ν1(')=170.4 cm(-1) for s-trans-isomer and ν1(')=139.7 cm(-1) for s-cis-isomer in the S1 state. The fundamental vibrational frequencies set has been found for isomers in the S0 and S1 states.

  16. Structural effect of the in situ generated titania on its ability to oxidize and capture the gas-phase elemental mercury.

    PubMed

    Lee, Tai Gyu; Hyun, Jung Eun

    2006-01-01

    Structural effect of the in situ generated TiO(2) sorbent particle was examined for its ability to capture elemental mercury under UV irradiation in a simulated combustion flue gas. Titania particles were prepared by thermal gas-phase oxidation of Titanium (IV) isopropoxide (TTIP) using a high temperature electric furnace reactor. The structural characteristics of the in situ generated TiO(2) at various synthesis temperatures were investigated; size distribution and the geometric mean diameter were measured using a scanning mobility particle sizer, while fractal dimension and radius of gyration were evaluated from the transmission electron microscopy images. Results from the Hg(0) capture experiment show that with increasing titania synthesis temperature, the overall aggregate size increases and the morphology becomes more open-structured to gas-phase Hg(0) and UV light, resulting in the improved mercury removal capability. PMID:15949836

  17. Permanent Electric Dipole Moments of Four Tryptamine Conformers in the Gas Phase. A New Diagnostic of Structure and Dynamics.

    NASA Astrophysics Data System (ADS)

    Pratt, David; Nguyen, Tri V.

    2006-03-01

    Rotationally resolved electronic spectroscopy in the gas phase, in the absence and presence of an applied electric field, has been used to determine the charge distribution of a cross section of the energy landscape of tryptamine (TRA). We report the magnitude and direction of the permanent electric dipole moments of the four TRA conformers GPyout, GPyup, GPhup and Antiup in their S0 and S1 electronic states. Each dipole moment is unique, providing a powerful new tool for conformational analysis of biomolecules in the gas phase. A comparison of the results for the different conformers of TRA reveals that the position and orientation of the ethylamine side chain plays a major role in determining both the permanent and induced electric dipole moments of the different species in both electronic states

  18. Permanent electric dipole moments of four tryptamine conformers in the gas phase: A new diagnostic of structure and dynamics

    NASA Astrophysics Data System (ADS)

    Nguyen, Tri V.; Pratt, David W.

    2006-02-01

    Rotationally resolved electronic spectroscopy in the gas phase, in the absence and presence of an applied electric field, has been used to determine the charge distribution of a cross section of the energy landscape of tryptamine (TRA). We report the magnitude and direction of the permanent electric dipole moments of the four TRA conformers GPyout, GPyup, GPhup, and Antiup in their S0 and S1 electronic states. Each dipole moment is unique, providing a powerful new tool for the conformational analysis of biomolecules in the gas phase. A comparison of the results for the different conformers of TRA reveals that the position and orientation of the ethylamine side chain play a major role in determining both the permanent and induced electric dipole moments of the different species in both electronic states.

  19. Molecular structure and conformational composition of 1,1-dichlorobutane: a gas-phase electron diffraction and ab initio investigation

    NASA Astrophysics Data System (ADS)

    Aarset, Kirsten; Hagen, Kolbjørn; Stølevik, Reidar

    1997-09-01

    Gas-phase electron diffraction data obtained at 23°C, together with results from ab initio molecular orbital calculations ( {HF}/{6-31 G(d)}). were used to determine the structure and conformational composition of 1,1-dichlorobutane. Of the five distinguishable conformers (AA, G + A, AG +, G + G + and G + G -), the G + A conformer was found to be the low-energy form, and the investigation also indicated that certain amounts of the AA and G + G - conformers might be present. The symbols describing the conformers refer to torsion about the C 1C 2 and C 2C 3 bonds, anti (A) with H 5C 1C 2C 3 and C 1C 2C 3C 4 torsion angles of 180° and gauche (G + or G -) with torsion angles of + 60° or 300° (-60°) respectively. The results for the principal distances ( rg) and angles (∠ α) from the combined electron diffraction/ab initio study for the G + A conformer, with estimated 2σ uncertainties, were as follows: r( C1 C2) = 1.521(4) Å, r( C2 C3) = 1.539(4) Å, r( C3 C4) = 1.546(4) Å, r( C Cl6) = 1.782(3) Å, r( CCl7) = 1.782(3) Å, = 1.106(6) Å, ∠C 1C 2C 3 = 114.4(13)°, ∠C 2C 3C 4 = 112.5(13)°, ∠CCCl 6 = 110.4(7)°, ∠CCCl 7 = 111.9(7)°, <∠CCH> = 108.9(47)°. Only average values for r(CC), r(CCl), r(CH), ∠CCC, ∠CCX and ∠CCH were determined in the least-square refinements; the differences between the values for these parameters in the same conformer and between the different conformers were kept constant at the values obtained from the ab initio molecular orbital calculations.

  20. Toward a Rational Design of Highly Folded Peptide Cation Conformations. 3D Gas-Phase Ion Structures and Ion Mobility Characterization

    NASA Astrophysics Data System (ADS)

    Pepin, Robert; Laszlo, Kenneth J.; Marek, Aleš; Peng, Bo; Bush, Matthew F.; Lavanant, Helène; Afonso, Carlos; Tureček, František

    2016-10-01

    Heptapeptide ions containing combinations of polar Lys, Arg, and Asp residues with non-polar Leu, Pro, Ala, and Gly residues were designed to study polar effects on gas-phase ion conformations. Doubly and triply charged ions were studied by ion mobility mass spectrometry and electron structure theory using correlated ab initio and density functional theory methods and found to exhibit tightly folded 3D structures in the gas phase. Manipulation of the basic residue positions in LKGPADR, LRGPADK, KLGPADR, and RLGPADK resulted in only minor changes in the ion collision cross sections in helium. Replacement of the Pro residue with Leu resulted in only marginally larger collision cross sections for the doubly and triply charged ions. Disruption of zwitterionic interactions in doubly charged ions was performed by converting the C-terminal and Asp carboxyl groups to methyl esters. This resulted in very minor changes in the collision cross sections of doubly charged ions and even slightly diminished collision cross sections in most triply charged ions. The experimental collision cross sections were related to those calculated for structures of lowest free energy ion conformers that were obtained by extensive search of the conformational space and fully optimized by density functional theory calculations. The predominant factors that affected ion structures and collision cross sections were due to attractive hydrogen bonding interactions and internal solvation of the charged groups that overcompensated their Coulomb repulsion. Structure features typically assigned to the Pro residue and zwitterionic COO-charged group interactions were only secondary in affecting the structures and collision cross sections of these gas-phase peptide ions.

  1. Toward a Rational Design of Highly Folded Peptide Cation Conformations. 3D Gas-Phase Ion Structures and Ion Mobility Characterization

    NASA Astrophysics Data System (ADS)

    Pepin, Robert; Laszlo, Kenneth J.; Marek, Aleš; Peng, Bo; Bush, Matthew F.; Lavanant, Helène; Afonso, Carlos; Tureček, František

    2016-07-01

    Heptapeptide ions containing combinations of polar Lys, Arg, and Asp residues with non-polar Leu, Pro, Ala, and Gly residues were designed to study polar effects on gas-phase ion conformations. Doubly and triply charged ions were studied by ion mobility mass spectrometry and electron structure theory using correlated ab initio and density functional theory methods and found to exhibit tightly folded 3D structures in the gas phase. Manipulation of the basic residue positions in LKGPADR, LRGPADK, KLGPADR, and RLGPADK resulted in only minor changes in the ion collision cross sections in helium. Replacement of the Pro residue with Leu resulted in only marginally larger collision cross sections for the doubly and triply charged ions. Disruption of zwitterionic interactions in doubly charged ions was performed by converting the C-terminal and Asp carboxyl groups to methyl esters. This resulted in very minor changes in the collision cross sections of doubly charged ions and even slightly diminished collision cross sections in most triply charged ions. The experimental collision cross sections were related to those calculated for structures of lowest free energy ion conformers that were obtained by extensive search of the conformational space and fully optimized by density functional theory calculations. The predominant factors that affected ion structures and collision cross sections were due to attractive hydrogen bonding interactions and internal solvation of the charged groups that overcompensated their Coulomb repulsion. Structure features typically assigned to the Pro residue and zwitterionic COO-charged group interactions were only secondary in affecting the structures and collision cross sections of these gas-phase peptide ions.

  2. Toward a Rational Design of Highly Folded Peptide Cation Conformations. 3D Gas-Phase Ion Structures and Ion Mobility Characterization.

    PubMed

    Pepin, Robert; Laszlo, Kenneth J; Marek, Aleš; Peng, Bo; Bush, Matthew F; Lavanant, Helène; Afonso, Carlos; Tureček, František

    2016-10-01

    Heptapeptide ions containing combinations of polar Lys, Arg, and Asp residues with non-polar Leu, Pro, Ala, and Gly residues were designed to study polar effects on gas-phase ion conformations. Doubly and triply charged ions were studied by ion mobility mass spectrometry and electron structure theory using correlated ab initio and density functional theory methods and found to exhibit tightly folded 3D structures in the gas phase. Manipulation of the basic residue positions in LKGPADR, LRGPADK, KLGPADR, and RLGPADK resulted in only minor changes in the ion collision cross sections in helium. Replacement of the Pro residue with Leu resulted in only marginally larger collision cross sections for the doubly and triply charged ions. Disruption of zwitterionic interactions in doubly charged ions was performed by converting the C-terminal and Asp carboxyl groups to methyl esters. This resulted in very minor changes in the collision cross sections of doubly charged ions and even slightly diminished collision cross sections in most triply charged ions. The experimental collision cross sections were related to those calculated for structures of lowest free energy ion conformers that were obtained by extensive search of the conformational space and fully optimized by density functional theory calculations. The predominant factors that affected ion structures and collision cross sections were due to attractive hydrogen bonding interactions and internal solvation of the charged groups that overcompensated their Coulomb repulsion. Structure features typically assigned to the Pro residue and zwitterionic COO-charged group interactions were only secondary in affecting the structures and collision cross sections of these gas-phase peptide ions. Graphical Abstract ᅟ.

  3. Toward a Rational Design of Highly Folded Peptide Cation Conformations. 3D Gas-Phase Ion Structures and Ion Mobility Characterization.

    PubMed

    Pepin, Robert; Laszlo, Kenneth J; Marek, Aleš; Peng, Bo; Bush, Matthew F; Lavanant, Helène; Afonso, Carlos; Tureček, František

    2016-10-01

    Heptapeptide ions containing combinations of polar Lys, Arg, and Asp residues with non-polar Leu, Pro, Ala, and Gly residues were designed to study polar effects on gas-phase ion conformations. Doubly and triply charged ions were studied by ion mobility mass spectrometry and electron structure theory using correlated ab initio and density functional theory methods and found to exhibit tightly folded 3D structures in the gas phase. Manipulation of the basic residue positions in LKGPADR, LRGPADK, KLGPADR, and RLGPADK resulted in only minor changes in the ion collision cross sections in helium. Replacement of the Pro residue with Leu resulted in only marginally larger collision cross sections for the doubly and triply charged ions. Disruption of zwitterionic interactions in doubly charged ions was performed by converting the C-terminal and Asp carboxyl groups to methyl esters. This resulted in very minor changes in the collision cross sections of doubly charged ions and even slightly diminished collision cross sections in most triply charged ions. The experimental collision cross sections were related to those calculated for structures of lowest free energy ion conformers that were obtained by extensive search of the conformational space and fully optimized by density functional theory calculations. The predominant factors that affected ion structures and collision cross sections were due to attractive hydrogen bonding interactions and internal solvation of the charged groups that overcompensated their Coulomb repulsion. Structure features typically assigned to the Pro residue and zwitterionic COO-charged group interactions were only secondary in affecting the structures and collision cross sections of these gas-phase peptide ions. Graphical Abstract ᅟ. PMID:27400696

  4. Structural exploration and Förster theory modeling for the interpretation of gas-phase FRET measurements: Chromophore-grafted amyloid-β peptides

    NASA Astrophysics Data System (ADS)

    Kulesza, Alexander; Daly, Steven; MacAleese, Luke; Antoine, Rodolphe; Dugourd, Philippe

    2015-07-01

    The distance-dependence of excitation energy transfer, e.g., being described by Förster theory (Förster resonance energy transfer (FRET)), allows the use of optical techniques for the direct observation of structural properties. Recently, this technique has been successfully applied in the gas phase. The detailed interpretation of the experimental FRET results, however, relies on the comparison with structural modeling. We therefore present a complete first-principles modeling approach that explores the gas-phase structure of chromophore-grafted peptides and achieves accurate predictions of FRET efficiencies. We apply the approach to amyloid-β 12-28 fragments, known to be involved in amyloid plaque formation connected to Alzheimer's disease. We sample structures of the peptides that are grafted with 5-carboxyrhodamine 575 (Rh575) and QSY-7 chromophores by means of replica-exchange molecular dynamics simulations upon an Amber-type forcefield parametrization as a function of the charge state. The generated ensembles provide chromophore-distance and -orientation distributions which are used with the spectral parameters of the Rh575/QSY-7 chromophores to model FRET-efficiencies for the systems. The theoretical values agree with the experimental average "action"-FRET efficiencies and motivate to use the herein reported parametrization, sampling, and FRET-modeling technique in future studies on the structural properties and aggregation-behavior of related systems.

  5. Structural exploration and Förster theory modeling for the interpretation of gas-phase FRET measurements: Chromophore-grafted amyloid-β peptides.

    PubMed

    Kulesza, Alexander; Daly, Steven; MacAleese, Luke; Antoine, Rodolphe; Dugourd, Philippe

    2015-07-14

    The distance-dependence of excitation energy transfer, e.g., being described by Förster theory (Förster resonance energy transfer (FRET)), allows the use of optical techniques for the direct observation of structural properties. Recently, this technique has been successfully applied in the gas phase. The detailed interpretation of the experimental FRET results, however, relies on the comparison with structural modeling. We therefore present a complete first-principles modeling approach that explores the gas-phase structure of chromophore-grafted peptides and achieves accurate predictions of FRET efficiencies. We apply the approach to amyloid-β 12-28 fragments, known to be involved in amyloid plaque formation connected to Alzheimer's disease. We sample structures of the peptides that are grafted with 5-carboxyrhodamine 575 (Rh575) and QSY-7 chromophores by means of replica-exchange molecular dynamics simulations upon an Amber-type forcefield parametrization as a function of the charge state. The generated ensembles provide chromophore-distance and -orientation distributions which are used with the spectral parameters of the Rh575/QSY-7 chromophores to model FRET-efficiencies for the systems. The theoretical values agree with the experimental average "action"-FRET efficiencies and motivate to use the herein reported parametrization, sampling, and FRET-modeling technique in future studies on the structural properties and aggregation-behavior of related systems. PMID:26178129

  6. Gas phase structures and charge localization in small aluminum oxide anions: Infrared photodissociation spectroscopy and electronic structure calculations.

    PubMed

    Song, Xiaowei; Fagiani, Matias R; Gewinner, Sandy; Schöllkopf, Wieland; Asmis, Knut R; Bischoff, Florian A; Berger, Fabian; Sauer, Joachim

    2016-06-28

    We use cryogenic ion trap vibrational spectroscopy in combination with quantum chemical calculations to study the structure of mono- and dialuminum oxide anions. The infrared photodissociation spectra of D2-tagged AlO1-4 (-) and Al2O3-6 (-) are measured in the region from 400 to 1200 cm(-1). Structures are assigned based on a comparison to simulated harmonic and anharmonic IR spectra derived from electronic structure calculations. The monoaluminum anions contain an even number of electrons and exhibit an electronic closed-shell ground state. The Al2O3-6 (-) anions are oxygen-centered radicals. As a result of a delicate balance between localization and delocalization of the unpaired electron, only the BHLYP functional is able to qualitatively describe the observed IR spectra of all species with the exception of AlO3 (-). Terminal Al-O stretching modes are found between 1140 and 960 cm(-1). Superoxo and peroxo stretching modes are found at higher (1120-1010 cm(-1)) and lower energies (850-570 cm(-1)), respectively. Four modes in-between 910 and 530 cm(-1) represent the IR fingerprint of the common structural motif of dialuminum oxide anions, an asymmetric four-member Al-(O)2-Al ring. PMID:27369513

  7. Gas phase structures and charge localization in small aluminum oxide anions: Infrared photodissociation spectroscopy and electronic structure calculations

    NASA Astrophysics Data System (ADS)

    Song, Xiaowei; Fagiani, Matias R.; Gewinner, Sandy; Schöllkopf, Wieland; Asmis, Knut R.; Bischoff, Florian A.; Berger, Fabian; Sauer, Joachim

    2016-06-01

    We use cryogenic ion trap vibrational spectroscopy in combination with quantum chemical calculations to study the structure of mono- and dialuminum oxide anions. The infrared photodissociation spectra of D2-tagged AlO1-4- and Al2O3-6- are measured in the region from 400 to 1200 cm-1. Structures are assigned based on a comparison to simulated harmonic and anharmonic IR spectra derived from electronic structure calculations. The monoaluminum anions contain an even number of electrons and exhibit an electronic closed-shell ground state. The Al2O3-6- anions are oxygen-centered radicals. As a result of a delicate balance between localization and delocalization of the unpaired electron, only the BHLYP functional is able to qualitatively describe the observed IR spectra of all species with the exception of AlO3-. Terminal Al-O stretching modes are found between 1140 and 960 cm-1. Superoxo and peroxo stretching modes are found at higher (1120-1010 cm-1) and lower energies (850-570 cm-1), respectively. Four modes in-between 910 and 530 cm-1 represent the IR fingerprint of the common structural motif of dialuminum oxide anions, an asymmetric four-member Al-(O)2-Al ring.

  8. Structures of lithiated lysine and structural analogues in the gas phase: effects of water and proton affinity on zwitterionic stability.

    PubMed

    Lemoff, Andrew S; Bush, Matthew F; O'Brien, Jeremy T; Williams, Evan R

    2006-07-13

    The structures of lithiated lysine, ornithine, and related molecules, both with and without a water molecule, are investigated using both density functional theory and blackbody infrared radiative dissociation experiments. The lowest-energy structure of lithiated lysine without a water molecule is nonzwitterionic; the metal ion interacts with both nitrogen atoms and the carbonyl oxygen. Structures in which lysine is zwitterionic are higher in energy by more than 29 kJ/mol. In contrast, the singly hydrated clusters with the zwitterionic and nonzwitterionic forms of lysine are more similar in energy, with the nonzwitterionic form more stable by only approximately 7 kJ/mol. Thus, a single water molecule can substantially stabilize the zwitterionic form of an amino acid. Analogous molecules that have methyl groups attached to either the N-terminus (NMeLys) or the side-chain amine (Lys(Me)) have proton affinities greater than that of lysine. In the lithiated clusters with a water molecule attached, the zwitterionic forms of NMeLys and Lys(Me) are calculated to be approximately 4 and approximately 11 kJ/mol more stable than the nonzwitterionic forms, respectively. Calculations of the potential-energy pathway for interconversion between the different forms of lysine in the lithiated complex indicate multiple stable intermediates with an overall barrier height of approximately 83 kJ/mol between the lowest-energy nonzwitterionic form and the most accessible zwitterionic form. Experimentally determined binding energies of water are similar for all these complexes and range from 57 to 64 kJ/mol. These results suggest that loss of a water molecule from the lysine complexes is both energetically and entropically favored compared to interconversion between the nonzwitterionic and zwitterionic structures. Comparisons to calculated binding energies of water to the various structures show that the experimental results are most consistent with the nonzwitterionic forms. PMID

  9. An Unexpected Gas-Phase Binding Motif for Metal Dication Complexation with Peptides: Irmpd Spectroscopic Structure Determination

    NASA Astrophysics Data System (ADS)

    Dunbar, Robert C.; Steill, Jeffrey; Polfer, Nicolas; Berden, Giel; Oomens, Jos

    2011-06-01

    The favorable orientation of the amide linkage and the aromatic side chain of N-terminal Phe or Trp leads to several favorable motifs for metal ion binding to dipeptides, having distinct characteristics in the IR spectrum. Infrared multiple photon photodissociation spectroscopy using the FELIX free electron laser has enabled clear resolution of these isomeric forms. The spectral patterns of complexes of small dications (Mg2+, Ni2+ and Co2+) reveal an unexpected new isomeric form, in which the metal ion displaces the amide hydrogen, forming a metal-nitrogen bond with covalent character which is unprecedented in such gas-phase complexes. Spectra of the ions were acquired by irradiating the cell of the Fourier-transform ion cyclotron resonance mass spectrometer with infrared light from the FELIX laser at wavelengths in the approximate range 500 to 1900 Cm-1.

  10. Structure enhancement methodology using theory and experiment: gas-phase molecular structures using a dynamic interaction between electron diffraction, molecular mechanics, and ab initio data.

    PubMed

    Kafka, Graeme R; Masters, Sarah L; Rankin, David W H

    2007-07-01

    A new method of incorporating ab initio theoretical data dynamically into the gas-phase electron diffraction (GED) refinement process has been developed to aid the structure determination of large, sterically crowded molecules. This process involves calculating a set of differences between parameters that define the positions of peripheral atoms (usually hydrogen), as determined using molecular mechanics (MM), and those which use ab initio methods. The peripheral-atom positions are then updated continually during the GED refinement process, using MM, and the returned positions are modified using this set of differences to account for the differences between ab initio and MM methods, before being scaled back to the average parameters used to define them, as refined from experimental data. This allows the molecule to adopt a completely asymmetric structure if required, without being constrained by the MM parametrization, whereas the calculations can be performed on a practical time scale. The molecular structures of tri-tert-butylphosphine oxide and tri-tert-butylphosphine imide have been re-examined using this new technique, which we call SEMTEX (Structure Enhancement Methodology using Theory and EXperiment).

  11. Structure and chemistry of the heteronuclear oxo-cluster [VPO4]•+: a model system for the gas-phase oxidation of small hydrocarbons.

    PubMed

    Dietl, Nicolas; Wende, Torsten; Chen, Kai; Jiang, Ling; Schlangen, Maria; Zhang, Xinhao; Asmis, Knut R; Schwarz, Helmut

    2013-03-01

    The heteronuclear oxo-cluster [VPO4](•+) is generated via electrospray ionization and investigated with respect to both its electronic structure as well as its gas-phase reactivity toward small hydrocarbons, thus permitting a comparison to the well-known vanadium-oxide cation [V2O4](•+). As described in previous studies, the latter oxide exhibits no or just minor reactivity toward small hydrocarbons, such as CH4, C2H6, C3H8, n-C4H10, and C2H4, while substitution of one vanadium by a phosphorus atom yields the reactive [VPO4](•+) ion; the latter brings about oxidative dehydrogenation (ODH) of saturated hydrocarbons, e.g., propane and butane as well as oxygen-atom transfer (OAT) to unsaturated hydrocarbons, e.g. ethene, at thermal conditions. Further, the gas-phase structure of [VPO4](•+) is determined by IR photodissociation spectroscopy and compared to that of [V2O4](•+). DFT calculations help to elucidate the reaction mechanism. The results underline the crucial role of phosphorus in terms of C-H bond activation of hydrocarbons by mixed VPO clusters.

  12. Structure and chemistry of the heteronuclear oxo-cluster [VPO4]•+: a model system for the gas-phase oxidation of small hydrocarbons.

    PubMed

    Dietl, Nicolas; Wende, Torsten; Chen, Kai; Jiang, Ling; Schlangen, Maria; Zhang, Xinhao; Asmis, Knut R; Schwarz, Helmut

    2013-03-01

    The heteronuclear oxo-cluster [VPO4](•+) is generated via electrospray ionization and investigated with respect to both its electronic structure as well as its gas-phase reactivity toward small hydrocarbons, thus permitting a comparison to the well-known vanadium-oxide cation [V2O4](•+). As described in previous studies, the latter oxide exhibits no or just minor reactivity toward small hydrocarbons, such as CH4, C2H6, C3H8, n-C4H10, and C2H4, while substitution of one vanadium by a phosphorus atom yields the reactive [VPO4](•+) ion; the latter brings about oxidative dehydrogenation (ODH) of saturated hydrocarbons, e.g., propane and butane as well as oxygen-atom transfer (OAT) to unsaturated hydrocarbons, e.g. ethene, at thermal conditions. Further, the gas-phase structure of [VPO4](•+) is determined by IR photodissociation spectroscopy and compared to that of [V2O4](•+). DFT calculations help to elucidate the reaction mechanism. The results underline the crucial role of phosphorus in terms of C-H bond activation of hydrocarbons by mixed VPO clusters. PMID:23432112

  13. Cation-Induced Stabilization of Protein Complexes in the Gas Phase: Mechanistic Insights From Hemoglobin Dissociation Studies

    NASA Astrophysics Data System (ADS)

    Liu, JiangJiang; Konermann, Lars

    2014-04-01

    Collision-induced dissociation (CID) of electrosprayed protein complexes usually involves asymmetric charge partitioning, where a single unfolded chain gets ejected that carries a disproportionately large fraction of charge. Using hemoglobin (Hb) tetramers as model system, we confirm earlier reports that bound metal ions can stabilize protein complexes under CID conditions. We examine the mechanism underlying this effect. Nonvolatile salts cause extensive adduct formation. Significant stabilization was observed for Mg2+ and Ca2+, whereas K+, Rb+, and Cs+ had no effect. Precursor ion selection was used to examine Hb subpopulations with well-defined metal binding levels. K+, Rb+, and Cs+-adducted tetramers eject monomers that carry roughly one-quarter of the metal ions that were bound to the precursor. This demonstrates that charge migration during CID is exclusively due to proton transfer, not metal ion transfer. Also, replacement of highly mobile charge carriers (protons) with less mobile species (metal ions) does not exert a stabilizing influence under the conditions used here. Interestingly, Hb carrying stabilizing ions (Mg2+ and Ca2+) generates monomeric CID products that are metal depleted. This effect is attributed to a combination of two factors: (1) Me2+ binding stabilizes Hb via formation of chelation bridges (e.g., R-COO- Me2+ -OOC-R); the more Me2+ a subunit contains the more stable it is. (2) More than ~90 % of the tetramers contain at least one subunit with a below-average number of Me2+. The prevalence of monomeric CID products with depleted Me2+ levels is caused by the tendency of these low metal-containing subunits to undergo preferential unfolding/ejection.

  14. The Effect of a Covalent and a Noncovalent Small-Molecule Inhibitor on the Structure of Abg β-Glucosidase in the Gas-Phase

    NASA Astrophysics Data System (ADS)

    Rajabi, Khadijeh; Douglas, D. J.

    2013-06-01

    The effects of binding two small-molecule inhibitors to Agrobacterium sp. strain ATCC 21400 (Abg) β-glucosidase on the conformations and stability of gas-phase ions of Abg have been investigated. Biotin-iminosugar conjugate (BIC) binds noncovalently to Abg while 2,4-dinitro-2-deoxy-2-fluoro-β- d-glucopyranoside (2FG-DNP) binds covalently with loss of DNP. In solution, Abg is a dimer. Mass spectra show predominantly dimer ions, provided care is taken to avoid dissociation of dimers in solution and dimer ions in the ion sampling interface. When excess inhibitor, either covalent or noncovalent, is added to solutions of Abg, mass spectra show peaks almost entirely from 2:2 inhibitor-enzyme dimer complexes. Tandem mass spectrometry experiments show similar dissociation channels for the apo-enzyme and 2FG-enzyme dimers. The +21 dimer produces +10 and +11 monomers. The internal energy required to dissociate the +21 2FG-enzyme to its monomers (767 ± 30 eV) is about 36 eV higher than that for the apo-enzyme dimer (731 ± 6 eV), reflecting the stabilization of the free enzyme dimer by the 2FG inhibitor. The primary dissociation channels for the noncovalent BIC-enzyme dimer are loss of neutral and charged BIC. The internal energy required to induce loss of BIC is 482 ± 8 eV, considerably less than that required to dissociate the dimers. For a given charge state, ions of the covalent and noncovalent complexes have about 15 % and 25 % lower cross sections, respectively, compared with the apo-enzyme. Thus, binding the inhibitors causes the gas-phase protein to adopt more compact conformations. Noncovalent binding surprisingly produces the greatest change in protein ion conformation, despite the weaker inhibitor binding.

  15. Electronic structure of BiGay(-) semiconductor clusters and the special stability of BiGa2- - A gas phase Zintl analogue

    NASA Astrophysics Data System (ADS)

    Gupta, Ujjwal; Ulises Reveles, J.; Melko, Joshua J.; Khanna, Shiv N.; Castleman, A. W., Jr.

    2009-01-01

    Here we present evidence that the gap between the highest occupied and lowest unoccupied molecular orbitals (HOMO-LUMO gap) can be tuned (1.12-1.89 eV) by changing the Ga composition of Bi 3Ga y anionic and neutral clusters, some of which display special stability. Collaboratively, mass spectrometry, photoelectron spectroscopy and computational results show that BiGa2- is a very stable cluster with a large calculated HOMO-LUMO gap of 1.89 eV, and can be viewed as a gas phase Zintl analogue of Sn52-, already synthesized in the solution phase. The stability of BiGa2- is further attributed to the fact that it has 12 valence electrons and possesses a closo structure in agreement with Wade's rules.

  16. Electronic Structure of Bi3Gay^- Semiconductor Clusters and the Special Stability of Bi3Ga2^- - A Gas Phase Zintl Analogue

    NASA Astrophysics Data System (ADS)

    Ulises Reveles, Jose; Gupta, Ujjwal; Melko, Joshua J.; Khanna, Shiv N.; Castleman, A. W., Jr.

    2009-03-01

    Here we present evidence that the gap between the highest occupied and lowest unoccupied molecular orbitals (HOMO-LUMO gap) can be tuned (1.12eV-1.89eV) by changing the Ga composition of Bi3Gay neutral and anionic clusters, some of which display special stability. Collaboratively, mass spectrometry, photoelectron spectroscopy and computational results show that Bi3Ga2^- is a very stable cluster with a large calculated HOMO-LUMO gap of 1.89 eV, and can be viewed as a gas phase Zintl analogue of Sn5^2-, already synthesized in the solution phase. The stability of Bi3Ga2^- is further attributed to the fact that it has 12 valence electrons and possesses a closo structure in agreement with Wade's rules.

  17. Irmpd Action Spectroscopy and Computational Approaches to Elucidate Gas-Phase Structures and Energetics of 2'-DEOXYCYTIDINE and Cytidine Sodium Complexes

    NASA Astrophysics Data System (ADS)

    Zhu, Yanlong; Hamlow, Lucas; He, Chenchen; Gao, Juehan; Oomens, Jos; Rodgers, M. T.

    2016-06-01

    The local structures of DNA and RNA are influenced by protonation, deprotonation and noncovalent interactions with cations. In order to determine the effects of Na+ cationization on the gas-phase structures of 2'-deoxycytidine, [dCyd+Na]+, and cytidine, [Cyd+Na]+, infrared multiple photon dissociation (IRMPD) action spectra of these sodium cationized nucleosides are measured over the range extending from 500 to 1850 wn using the FELIX free electron laser. Complementary electronic structure calculations are performed to determine the stable low-energy conformations of these complexes. Geometry optimizations, frequency analyses, and IR spectra of these species are determined at the B3LYP/6-311+G(d,p) level of theory. Single-point energies are calculated at the B3LYP/6-311+G(2d,2p) level of theory to determine the relative stabilities of these conformations. Comparison of the measure IRMPD action spectra and computed linear IR spectra enable the conformations accessed in the experiments to be elucidated. For both cytosine nucleosides, tridentate binding of the Na+ cation to the O2, O4' and O5' atoms of the nucleobase and sugar is observed. Present results for the sodium cationized nucleosides are compared to results for the analogous protonated forms of these nucleosides to elucidate the effects of multiple chelating interactions with the sodium cation vs. hydrogen bonding interactions in the protonated systems on the structures and stabilities of these nucleosides.

  18. Low symmetry in molecules with heavy peripheral atoms. The gas-phase structure of perfluoro(methylcyclohexane), C6F11CF3.

    PubMed

    Kafka, Graeme R; Masters, Sarah L; Wann, Derek A; Robertson, Heather E; Rankin, David W H

    2010-10-21

    When refining structures using gas electron diffraction (GED) data, assumptions are often made in order to reduce the number of required geometrical parameters. Where these relate to light, peripheral atoms there is little effect on the refined heavy-atom structure, which is well defined by the GED data. However, this is not the case when heavier atoms are involved. We have determined the gas-phase structure of perfluoro(methylcyclohexane), C(6)F(11)CF(3), using three different refinement methods and have shown that our new method, which makes use of both MP2 and molecular mechanics (MM) calculations to restrain the peripheral-atom geometry, gives a realistic structure without the need for damaging constraints. Only the conformer with the CF(3) group in an equatorial position was considered, as ab initio calculations showed this to be 25 kJ mol(-1) lower in energy than the axial conformer. Refinements combining both high-level and low-level calculations to give constraints were superior both to those based only on molecular mechanics and to those in which assumptions about the geometry were imposed.

  19. A carbon foam with a bimodal micro–mesoporous structure prepared from larch sawdust for the gas-phase toluene adsorption

    SciTech Connect

    Liu, Shouxin; Huang, Zhanhua; Wang, Rui

    2013-07-15

    Highlights: ► Network carbon foam containing a bimodal pore distribution was prepared from Larch. ► Liquefaction route was used for the preparation of morphology controllable carbon. ► Pore structure of carbon foam was controlled through KOH activation. - Abstract: A carbon foam with a bimodal micro–mesopore distribution, was prepared by submitting larch sawdust to liquefaction, resinification, foaming, carbonization and KOH activation. The morphology, pore texture and crystal microstructure was characterized by scanning and transmission electron microscopy, nitrogen adsorption analysis and X-ray powder diffraction. A honeycomb structure with adjacent cells was observed for the precursor of carbon foam. After KOH activation, the cell wall of precursor shrunk and broke. This lead to the formation of a well-connected 3D network and developed ligament pore structure (surface area of 554–1918 m{sup 2}/g) containing bimodal pores, 2.1 and 3.9 nm in diameter. The porous carbon foam prepared at 700 °C exhibited a much higher gas-phase toluene removal than commercial activated carbon fiber owing to the 3D network and bimodal pore structure.

  20. Secondary structures of Val-Phe and Val-Tyr(Me) peptide chains in the gas phase: effect of the nature of the protecting groups

    NASA Astrophysics Data System (ADS)

    Chin, Wutharath; Dognon, Jean-Pierre; Piuzzi, François; Dimicoli, Iliana; Mons, Michel

    Recent experimental gas-phase studies of very similar peptide chain models (Ac-Val-Tyr(Me)-NHMe and Ac-Val-Phe-NH2) have led to different assignments for the secondary structures adopted: β-strand and β-turn, respectively. We present a discussion of the possible causes for such different behaviour in the light of quantum chemistry calculations. The consistent set of data presently obtained (relative energies and IR calculated spectra) leads us to propose the same structural assignment for the experimentally observed Val-Tyr(Me) and Val-Phe peptide chains, i.e. a β-turn conformation. In addition, calculations also suggest that the nature of the chemical protection on the C-terminal (-NHMe vs. -NH2) of the chain model does not affect its conformational preference, nor its structure or its energetics, which suggests the less simple, but more informative, -NH2-protected models for the determination of the intrinsic structural properties of a peptide chain.

  1. Manual gas-phase isothiocyanate degradation.

    PubMed

    Brandt, W F; Frank, G

    1988-02-01

    We describe a manual gas-phase isothiocyanate degradation procedure for the primary structure determination of proteins and peptides. The proteins and peptides are applied to a polybrene-coated glass fiber filter wedged into a small glass column. The phenylisothiocyanate is directly pipetted onto the filter disk. The coupling and cleavage reactions are performed in small desiccators containing trimethylamine and trifluoroacetic acid vapors, respectively. The wash and extraction steps are performed by allowing the suitable solvents to percolate through the filter disk. The extracted anilinothiazolinone is then converted to the phenylthiohydantoin and identified by any one of a number of described methods. Our results show that this method is very sensitive and that the reactions proceed faster than those of the published automated procedure. No expensive equipment is required and the manual degradation can be performed by a laboratory assistant. A large number of samples can be simultaneously subjected to the degradation under identical conditions, making this an ideal method for physicochemical investigations into the isothiocyanate degradation. We also use this method to screen HPLC fractions after enzymatic protein fragmentation. Manually sequenced glass filters can be transferred to the automated instrument for more extended degradations.

  2. The molecular structure of tetramethyldiarsine, As 2 (CH 3) 4, in the gas phase as determined by electron diffraction

    NASA Astrophysics Data System (ADS)

    Downs, Anthony J.; Hunt, Nicholas I.; McGrady, G. Sean; Rankin, David W. H.; Robertson, Heather E.

    1991-08-01

    The structure of gaseous tetramethyldiarsine, As 2(CH 3) 4, has been determined by electron diffraction. At room temperature (about 290 K) the vapour consists of a mixture comprising about 60% of the gauche and 40% of the trans conformer, a finding consistent with the results of earlier spectroscopic studies of the liquid. Salient parameters of the structure are: r(AsAs) = 243.3(0.2) and r(AsC) = 197.3(0.2) pm; ∠AsAsC = 95.4(0.5), ∠CAsC = 95.3(1.1) and ∠AsCH = 109.3(0.9)°. These and other features are discussed in the light of the conformations and dimensions of related compounds of the Group V elements, e.g. P 2 (CH 3) 4 and As (CH 3) 3.

  3. Prioritizing testing of organic compounds detected as gas phase air pollutants: structure-activity study for human contact allergens.

    PubMed Central

    Johnson, R; Macina, O T; Graham, C; Rosenkranz, H S; Cass, G R; Karol, M H

    1997-01-01

    Organic compounds that are used or generated anthropogenically in large quantities in cities can be identified through their presence in the urban atmosphere and in air pollutant source emissions. Compounds identified by this method were screened to evaluate their potential to act as contact allergens. The CASE and MULTICASE computer programs, which are based on the detection of structure-activity relationships (SAR), were used to evaluate this potential. These relationships first are determined by comparing chemical structures to biological activity within a learning set comprised of 458 compounds, each of which had been tested experimentally in human trials for its sensitization potential. Using the information contained in this learning set, CASE and MULTICASE predicted the activity of 238 compounds found in the atmosphere for their ability to act as contact allergens. The analysis finds that 21 of 238 compounds are predicted to be active contact allergens (probability >0.5), with potencies ranging from mild to very strong. The compounds come from chemical classes that include chlorinated aromatics and chlorinated hydrocarbons, N-containing compounds, phenols, alkenes, and an S-containing compound. Using the measured airborne concentrations or emission rates of these compounds as an indication of the extent of their use, together with their predicted potencies, provides an efficient method to prioritize the experimental assessment of contact sensitization of untested organic compounds that can be detected as air pollutants. Images Figure 1. PMID:9300925

  4. Gas-Phase Structure of Amyloid-β (12 - 28) Peptide Investigated by Infrared Spectroscopy, Electron Capture Dissociation and Ion Mobility Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Le, Thi Nga; Poully, Jean Christophe; Lecomte, Frédéric; Nieuwjaer, Nicolas; Manil, Bruno; Desfrançois, Charles; Chirot, Fabien; Lemoine, Jerome; Dugourd, Philippe; van der Rest, Guillaume; Grégoire, Gilles

    2013-12-01

    The gas-phase structures of doubly and triply protonated Amyloid-β12-28 peptides have been investigated through the combination of ion mobility (IM), electron capture dissociation (ECD) mass spectrometry, and infrared multi-photon dissociation (IRMPD) spectroscopy together with theoretical modeling. Replica-exchange molecular dynamics simulations were conducted to explore the conformational space of these protonated peptides, from which several classes of structures were found. Among the low-lying conformers, those with predicted diffusion cross-sections consistent with the ion mobility experiment were further selected and their IR spectra simulated using a hybrid quantum mechanical/semiempirical method at the ONIOM DFT/B3LYP/6-31 g(d)/AM1 level. In ECD mass spectrometry, the c/z product ion abundance (PIA) has been analyzed for the two charge states and revealed drastic differences. For the doubly protonated species, N - Cα bond cleavage occurs only on the N and C terminal parts, while a periodic distribution of PIA is clearly observed for the triply charged peptides. These PIA distributions have been rationalized by comparison with the inverse of the distances from the protonated sites to the carbonyl oxygens for the conformations suggested from IR and IM experiments. Structural assignment for the amyloid peptide is then made possible by the combination of these three experimental techniques that provide complementary information on the possible secondary structure adopted by peptides. Although globular conformations are favored for the doubly protonated peptide, incrementing the charge state leads to a conformational transition towards extended structures with 310- and α-helix motifs.

  5. Gas-phase chemical dynamics

    SciTech Connect

    Weston, R.E. Jr.; Sears, T.J.; Preses, J.M.

    1993-12-01

    Research in this program is directed towards the spectroscopy of small free radicals and reactive molecules and the state-to-state dynamics of gas phase collision, energy transfer, and photodissociation phenomena. Work on several systems is summarized here.

  6. Microwave Spectrum for a Second Higher Energy Conformer of Cyclopropanecarboxylic Acid and Determination of the Gas Phase Structure of the Ground State.

    PubMed

    Pejlovas, Aaron M; Lin, Wei; Kukolich, Stephen G

    2015-10-01

    Microwave spectra for a higher-energy conformer of cyclopropanecarboxylic acid (CPCA) were measured using a Flygare-Balle-type pulsed-beam Fourier transform microwave spectrometer. The rotational constants (in megahertz) and centrifugal distortion constants (in kilohertz) for this higher-energy conformer are A = 7452.3132(57), B = 2789.8602(43), C = 2415.0725(40), DJ = 0.29(53), and DJK = 2.5(12). Differences between rotational constants for this excited-state conformation and the ground state are primarily due to the acidic OH bond moving from a position cis relative to the cyclopropyl group about the C1-C9 bond to the more stable trans conformation. Calculations indicate that the relative abundance of the higher-energy state should be 15% to 17% at room temperature, but the observed relative abundance for the supersonic expansion conditions is about 1%. The measurements of rotational transitions for the trans form of CPCA were extended to include all of the unique (13)C singly substituted positions. These measurements, along with previously measured transitions of the parent and -OD isotopologues, were used to determine a best-fit gas-phase structure.

  7. Gas phase fragmentation of eta2 coordinated aldehydes in [VO2(eta2-OCHR)]-: aldehyde structure dictates the nature of the products.

    PubMed

    Waters, Tom; Khairallah, George N; O'Hair, Richard A J

    2009-09-28

    The gas phase fragmentation reactions of eta2 coordinated aldehydes in [VO2(eta2-OCHR)]-, which have previously been shown to play a role in the catalytic oxidation of alcohols to aldehydes, were examined using a combination of isotope labelling experiments and collision induced dissociation in a quadrupole ion trap mass spectrometer. The experimental data were interpreted with the aid of density functional theory calculations (DFT). The types of fragmentation reactions observed depend on the nature of the R group. When R = H, the dominant fragmentation channel involves formation of [VO2H2]-via loss of CO. Minor losses of H2 and CH2O are also observed. When R = Me, loss of H2 is observed to give rise to an ion at m/z 125 corresponding to the formula [V, O3, C2, H2]-. DFT calculations on the [VO2(eta2-OCHR)]- and their CID reaction products have identified minimum energy structures for all reactants and products involved. DFT calculations also provided insights into key intermediates on the potential energy surface associated with these fragmentation reactions, including: [(H2)VO2(CO)]- in the case of R = H; and [HVO2(eta1-OCHCH2)]- in the case of R = Me. The results presented provide insights into potential side reactions occurring during catalysis of alcohols over vanadium oxides, for instance, the over-oxidation of methanol to carbon monoxide. PMID:19727457

  8. Gas-phase rate coefficients for the reactions of NO 3, OH and O 3 with α, β-unsaturated esters and ketones: Structure-activity relations (SARs)

    NASA Astrophysics Data System (ADS)

    Pfrang, Christian; King, Martin D.; Canosa-Mas, Carlos E.; Flugge, Mark; Wayne, Richard P.

    Gas-phase rate coefficients for the atmospherically important reactions of NO 3, OH and O 3 are predicted for 55 α, β-unsaturated esters and ketones. The rate coefficients were calculated using a correlation described previously [Pfrang, C., King, M.D., C. E. Canosa-Mas, C.E., Wayne, R.P., 2006. Atmospheric Environment 40, 1170-1179]. These rate coefficients were used to extend structure-activity relations for predicting the rate coefficients for the reactions of NO 3, OH or O 3 with alkenes to include α, β-unsaturated esters and ketones. Conjugation of an alkene with an α, β-keto or α, β-ester group will reduce the value of a rate coefficient by a factor of ˜110, ˜2.5 and ˜12 for reaction with NO 3, OH or O 3, respectively. The actual identity of the alkyl group, R, in -C(O)R or -C(O)OR has only a small influence. An assessment of the reliability of the SAR is given that demonstrates that it is useful for reactions involving NO 3 and OH, but less valuable for those of O 3 or peroxy nitrate esters.

  9. Gas-Phase Molecular Structure of Nopinone and its Water Complexes Studied by Microwave Fourier Transform Spectroscopy and Quantum Chemical Calculations

    NASA Astrophysics Data System (ADS)

    Neeman, Elias M.; Aviles Moreno, Juan-Ramon; Huet, T. R.

    2016-06-01

    Several monoterpenes and terpenoids are biogenic volatile organic compounds which are emitted in the atmosphere, where they react with OH, O_3 and NO_x etc. to give rise to several oxidation and degradation products. Their decomposition products are a major source of secondray organic aerosol (SOA). Spectroscopic information on these atmospheric species is still very scarce. The rotational spectrum of nopinone (C_9H14O) one of the major oxidation products of β-pinene, and of its water complexes were recorded in a supersonic jet expansion with a Fourier transform microwave spectrometer over the range 2-20 GHz. The structure of the unique stable conformer of the nopinone was optimized using density functional theory and ab initio calculations. Signals from the parent species and from the 13C and 18O isotopomers were observed in natural abundance. A magnetic hyperfine structure associated with the pairs of hydrogen nuclei in the methylene groups was observed and modeled. The structures of several conformers of the nopinone-water complexes with up to three molecules of water were optimized using density functional theory and ab initio calculations. The energetically most stable of calculated conformers were observed and anlyzed. The rotational and centrifugal distortion parameters were fitted to a Watson's Hamiltonian in the A-reduction. The present work provides the first spectroscopic characterization of nopinone and its water complexes in the gas phase. A. Calogirou, B.R. Larsen, and D. Kotzias, Atmospheric Environment, 33, 1423-1439, (1999) P. Paasonen et al., Nat. Geosci., 6, 438-442 (2013) D. Zhang and R. Zhang The Journal of Chemical Physics, 122, 114308, (2005) R. Winterhalter et al. Journal of Atmospheric Chemistry, 35, 165-197, (2000)

  10. Transition metals as electron traps. I. Structures, energetics, electron capture, and electron-transfer-induced dissociations of ternary copper-peptide complexes in the gas phase.

    PubMed

    Turecek, Frantisek; Jones, Jace W; Holm, Anne I S; Panja, Subhasis; Nielsen, Steen Brøndsted; Hvelplund, Preben

    2009-05-01

    Electron-induced dissociations of gas-phase ternary copper-2,2'-bipyridine complexes of Gly-Gly-Gly and Gly-Gly-Leu were studied on a time scale ranging from 130 ns to several milliseconds using a combination of charge-reversal ((+)CR(-)) and electron-capture-induced dissociation (ECID) measured on a beam instrument and electron capture dissociation (ECD) measured in a Penning trap. Charge-reduced intermediates were observed on the short time scale in the (+)CR(-) and ECID experiments but not in ECD. Ion dissociations following electron transfer or capture mostly occurred by competitive bpy or peptide ligand loss, whereas peptide backbone fragmentations were suppressed in the presence of the ligated metal ion. Extensive electron structure theory calculations using density functional theory and large basis sets provided optimized structures and energies for the precursor ions, charge-reduced intermediates, and dissociation products. The Cu complexes underwent substantial structure changes upon electron capture. Cu was calculated to be pentacoordinated in the most stable singly charged complexes of the [Cu(peptide-H)bpy](+*) type where it carried a approximately +1 atomic charge. Cu coordination in charge-reduced [Cu(peptide-H)bpy] intermediates depended on the spin state. The themodynamically more stable singlet states had tricoordinated Cu, whereas triplet states had a tetracoordinated Cu. Cu was tricoordinated in stable [Cu(peptide-H)bpy](-*) products of electron transfer. [Cu(peptide)bpy](2+*) complexes contained the peptide ligand in a zwitterionic form while Cu was tetracoordinated. Upon electron capture, Cu was tri- or tetracoordinated in the [Cu(peptide)bpy](+) charge-reduced analogs and the peptide ligands underwent prototropic isomerization to canonical forms. The role of excited singlet and triplet electronic states is assessed. PMID:19132713

  11. Gas-phase metalloprotein complexes interrogated by ion mobility-mass spectrometry

    NASA Astrophysics Data System (ADS)

    Faull, Peter A.; Korkeila, Karoliina E.; Kalapothakis, Jason M.; Gray, Andrew; McCullough, Bryan J.; Barran, Perdita E.

    2009-06-01

    Gas-phase biomolecular structure may be explored through a number of analytical techniques. Ion mobility-mass spectrometry (IM-MS) continues to prove itself as a sensitive and reliable bioanalytical tool for gas-phase structure determination due to intense study and development over the past 15 years. A vast amount of research interest, especially in protein and peptide conformational studies has generated a wealth of structural information for biological systems from small peptides to megadalton-sized biomolecules. In this work, linear low field IM-MS has been used to study gas-phase conformations and determine rotationally averaged collision cross-sections of three metalloproteins--cytochrome c, haemoglobin and calmodulin. Measurements have been performed on the MoQToF, a modified QToF 1 instrument (Micromass UK Ltd., Manchester, UK) modified in house. Gas-phase conformations and cross-sections of multimeric cytochrome c ions of the form [xM + nH+]n+ for x = 1-3 (monomer to trimer) have been successfully characterised and measured. We believe these to be the first reported collision cross-sections of higher order multimeric cytochrome c. Haemoglobin is investigated to obtain structural information on the associative mechanism of tetramer formation. Haemoglobin molecules, comprising apo- and holo-monomer chains, dimer and tetramer are transferred to the gas phase under a range of solution conditions. Structural information on the proposed critical intermediate, semi-haemoglobin, is reported. Cross-sections of the calcium binding protein calmodulin have been obtained under a range of calcium-bound conditions. Metalloprotein collision cross-sections from ion mobility measurements are compared with computationally derived values from published NMR and X-ray crystallography structural data. Finally we consider the change in the density of the experimentally measured rotationally averaged collision cross-section for compact geometries of the electrosprayed proteins.

  12. Understanding the structure and dynamic of odorants in the gas phase using a combination of microwave spectroscopy and quantum chemical calculations

    NASA Astrophysics Data System (ADS)

    Mouhib, Halima

    2014-07-01

    This tutorial is an introduction for PhD students and researchers who intend to start their future work in the field of microwave spectroscopy to investigate structural and dynamical aspects of isolated molecular systems in the gas phase. Although the presented case studies are related to odorants, i.e., volatile molecules that possess a noticeable scent, the background and applications of the method can be transferred to any other resembling molecular system. In the early days, microwave spectroscopy was mainly related to the structure determination of very small systems such as OCS or ammonia, where the bond lengths could be determined with high accuracy by measuring the different isotopic species of the molecules. Nowadays, the method is far more advanced and is also used to tackle various fundamental molecular problems in different fields such as physical chemistry and molecular physics. Interesting questions that can be investigated concern, e.g., the molecular structure, i.e., the different conformations, not only of the isolated molecule but also of van der Waals complexes with water, noble gases or other molecules. The dynamical and intra- or intermolecular effects can be straightforwardly observed without the influence of the environment as in the condensed phase. This evolution was only achieved by using quantum chemical methods as a complementary tool to elude the necessity of isotopologues for structure determination, which cannot be realized for large systems (>5 atoms). The combination of microwave spectroscopy and quantum chemical calculations is the method of choice when it comes to sampling the conformational space of molecules. This is particularly the case when small energy differences make it difficult to determine the conformers of the lowest energy using computational methods alone. Although quantum chemical calculations are important for the validation of microwave spectra, the focus of the tutorial is set on the experimental part of the

  13. Gas-phase doubly charged complexes of cyclic peptides with copper in +1, +2 and +3 formal oxidation states: formation, structures and electron capture dissociation.

    PubMed

    Afonso, Carlos; Tabet, Jean-Claude; Giorgi, Gianluca; Tureček, František

    2012-02-01

    Copper complexes with a cyclic D-His-β-Ala-L-His-L-Lys and all-L-His-β-Ala-His-Lys peptides were generated by electrospray which were doubly charged ions that had different formal oxidation states of Cu(I), Cu(II) and Cu(III) and different protonation states of the peptide ligands. Electron capture dissociation showed no substantial differences between the D-His and L-His complexes. All complexes underwent peptide cross-ring cleavages upon electron capture. The modes of ring cleavage depended on the formal oxidation state of the Cu ion and peptide protonation. Density functional theory (DFT) calculations, using the B3LYP with an effective core potential at Cu and M06-2X functionals, identified several precursor ion structures in which the Cu ion was threecoordinated to pentacoordinated by the His and Lys side-chain groups and the peptide amide or enolimine groups. The electronic structure of the formally Cu(III) complexes pointed to an effective Cu(I) oxidation state with the other charge residing in the peptide ligand. The relative energies of isomeric complexes of the [Cu(c-HAHK + H)](2+) and [Cu(c-HAHK - H)](2+) type with closed electronic shells followed similar orders when treated by the B3LYP and M06-2X functionals. Large differences between relative energies calculated by these methods were obtained for open-shell complexes of the [Cu(c-HAHK)](2+) type. Charge reduction resulted in lowering the coordination numbers for some Cu complexes that depended on the singlet or triplet spin state being formed. For [Cu(c-HAHK - H)](2+) complexes, solution H/D exchange involved only the N-H protons, resulting in the exchange of up to seven protons, as established by ultra-high mass resolution measurements. Contrasting the experiments, DFT calculations found the lowest energy structures for the gas-phase ions that were deprotonated at the peptide C(α) positions.

  14. The gas-phase molecular structure of 1,1-diethynylsilacyclobutane as determined by means of electron diffraction and ab initio calculations

    NASA Astrophysics Data System (ADS)

    Dakkouri, Marwan; Grosser, Martin

    2002-06-01

    As a continuation of our systematic investigation of the effect of substituents on the ring geometry and dynamics in silacyclobutanes and in order to explore the role of the silicon atom as a mediator for electronic interactions between the attached fragments, we studied the molecular structure of 1,1-diethynylsilacyclobutane (DESCB) by means of gas-phase electron diffraction and ab initio calculations. The structural refinement of the electron diffraction data yielded the following bond lengths ( ra) and bond angles (uncertainties are 3σ): r( Si- C)=1.874(2) Å, r( Si- C)=1.817(1) Å, r(- C C-)=1.209(1) Å, r( C- C)=1.563(2) Å, ∠(C-Si-C)=79.2(6)°, ∠(C-Si-C)=106.5(6)°. The geminal Si-CC moieties were found to be bent outwards by 3.1(15)° and the puckering angle was determined to be 30.0(15)°. The evidently short Si-C bond length, which was also reproduced by the ab initio calculations, could be rationalized as being the consequence of the electronic interaction between the outer π charges of the triple bond and the 3pπ orbitals at the silicon atom. It is also likely that the conjugation of the geminal ethynyl groups leads to an enhancement of this bond contraction. Electrostatic interactions and the subsequent reduction of the covalent radius of the silicon atom may also contribute to this bond shortening. It has been found that the endocyclic Si-C bond length fits nicely within a scheme describing a monotonous decrease of the Si-C bond length with the increase of the electronegativity of the substituent in various geminally substituted silacyclobutanes. A series of related silacyclobutanes and acyclic diethynylsilanes have been studied by applying various ab initio methods and their optimized structures were compared to the structure of DESCB. Among these compounds are 1,1-dicyanosilacyclobutane (DCYSCB), which is isoelectronic to DESCB, 1,1-diethynylcyclobutane (DECB) which is isovalent to DESCB, monoethynylsilacyclobutane (MESCB

  15. Liquid phase separation of proteins based on electrophoretic effects in an electrospray setup during sample introduction into a gas-phase electrophoretic mobility molecular analyzer (CE–GEMMA/CE–ES–DMA)

    PubMed Central

    Weiss, Victor U.; Kerul, Lukas; Kallinger, Peter; Szymanski, Wladyslaw W.; Marchetti-Deschmann, Martina; Allmaier, Günter

    2014-01-01

    Nanoparticle characterization is gaining importance in food technology, biotechnology, medicine, and pharmaceutical industry. An instrument to determine particle electrophoretic mobility (EM) diameters in the single-digit to double-digit nanometer range receiving increased attention is the gas-phase electrophoretic mobility molecular analyzer (GEMMA) separating electrophoretically single charged analytes in the gas-phase at ambient pressure. A fused-silica capillary is used for analyte transfer to the gas-phase by means of a nano electrospray (ES) unit. The potential of this capillary to separate analytes electrophoretically in the liquid phase due to different mobilities is, at measurement conditions recommended by the manufacturer, eliminated due to elevated pressure applied for sample introduction. Measurements are carried out upon constant feeding of analytes to the system. Under these conditions, aggregate formation is observed for samples including high amounts of non-volatile components or complex samples. This makes the EM determination of individual species sometimes difficult, if not impossible. With the current study we demonstrate that liquid phase electrophoretic separation of proteins (as exemplary analytes) occurs in the capillary (capillary zone electrophoresis, CE) of the nano ES unit of the GEMMA. This finding was consecutively applied for on-line desalting allowing EM diameter determination of analytes despite a high salt concentration within samples. The present study is to our knowledge the first report on the use of the GEMMA to determine EM diameters of analytes solubilized in the ES incompatible electrolyte solutions by the intended use of electrophoresis (in the liquid phase) during sample delivery. Results demonstrate the proof of concept of such an approach and additionally illustrate the high potential of a future on-line coupling of a capillary electrophoresis to a GEMMA instrument. PMID:25109866

  16. Molecular structures and conformational compositions of 2-chlorobutane and 2-bromobutane; an investigation using gas-phase electron-diffraction data and ab initio molecular orbital calculations

    NASA Astrophysics Data System (ADS)

    Aarset, Kirsten; Hagen, Kolbjørn; Stølevik, Reidar

    2001-06-01

    The structure and conformational composition of 2-chlorobutane and 2-bromobutane have been studied by gas-phase electron diffraction (GED) at 25°C, together with ab initio molecular orbital calculations (HF/6-311+G(d,p)). These molecules may exist as three distinguishable conformers (G+, A, and G-). The symbols refer to anti (A) with a torsion angle Φ2(X 8-C 2-C 3-C 4) of about 180° and gauche (G+ and G-) with torsion angles Φ2(X 8-C 2-C 3-C 4) of about +60° and 300°(-60°), respectively. It was not possible; from our GED-data alone, to accurately determine the conformational composition because the distance distributions for two of the conformers (G+ and G-) are very similar. The conformational composition for 2-chlorobutane obtained from the ab initio calculations (G+ 62%, A 25% G- 13%) was found to fit the experimental data quite well. For 2-bromobutane the ab initio calculated conformational composition (G+ 58%, A 28% G- 14%) did not, however, fit the experimental data. Here a much better fit was obtained by using only 10% of the A conformer and using the relative energy for the two gauche conformers, as obtained in the ab initio molecular orbital calculations, to calculate the relative amounts of the two gauche forms (G+ 73%, A 10% G- 17%). The results for the principal distances ( rg) and angles ∠ α for the G+ conformer of 2-chlorobutane, with estimated 2 σ uncertainties, obtained from the combined GED/ab initio study are: r( C1- C2)=1.524(3) Å, r( C2- C3)=1.528(3) Å, r( C3- C4)=1.539(3) Å, r( C- Cl)=1.812(3) Å, r( C- H) ave=1.098(4) Å, ∠C 1C 2C 3=111.5(16)°, ∠C 2C 3C 4=113.3(5)°, ∠C 1C 2C1=110.4(9)°. The results for the G+ conformer of 2-bromobutane are: r( C1- C2)=1.526(4) Å, r( C2- C3)=1.530(4) Å, r( C3- C4)=1.540(4) Å, r( C- Br)=1.982(5) Å, r( C- H) ave=1.111(8) Å, ∠C 1C 2C 3=112.5(16)°, ∠C 2C 3C 4=114.6(15)°, ∠C 1C 2Br=110.1(16)°. Only average values for r(C-C), r(C-H), ∠CCC, and ∠CCH could be determined in the

  17. Mapping Protein-Ligand Interactions in the Gas Phase Using a Functional Group Replacement Strategy. Comparison of CID and BIRD Activation Methods

    NASA Astrophysics Data System (ADS)

    Deng, Lu; Kitova, Elena N.; Klassen, John S.

    2013-07-01

    Intermolecular interactions in the gaseous ions of two protein-ligand complexes, a single chain antibody (scFv) and its trisaccharide ligand (α-D-Gal p-(1→2)-[α-D-Abe p-(1→3)]-α-Man p-OCH3, L1) and streptavidin homotetramer (S4) and biotin (B), were investigated using a collision-induced dissociation (CID)-functional group replacement (FGR) strategy. CID was performed on protonated ions of a series of structurally related complexes based on the (scFv + L1) and (S4 + 4B) complexes, at the +10 and +13 charge states, respectively. Intermolecular interactions were identified from decreases in the collision energy required to dissociate 50 % of the reactant ion (Ec50) upon modification of protein residues or ligand functional groups. For the (scFv + L1)10+ ion, it was found that deoxygenation of L1 (at Gal C3 and C6 and Man C4 and C6) or mutation of His101 (to Ala) resulted in a decrease in Ec50 values. These results suggest that the four hydroxyl groups and His101 participate in intermolecular H-bonds. These findings agree with those obtained using the blackbody infrared radiative dissociation (BIRD)-FGR method. However, the CID-FGR method failed to reveal the relative strengths of the intermolecular interactions or establish Man C4 OH and His101 as an H-bond donor/acceptor pair. The CID-FGR method correctly identified Tyr43, but not Ser27, Trp79, and Trp120, as a stabilizing contact in the (S4 + 4B)13+ ion. In fact, mutation of Trp79 and Trp120 led to an increase in the Ec50 value. Taken together, these results suggest that the CID-FGR method, as implemented here, does not represent a reliable approach for identifying interactions in the gaseous protein-ligand complexes.

  18. Density functional theory investigations on the structure and dissolution mechanisms for cellobiose and xylan in an ionic liquid: gas phase and cluster calculations.

    PubMed

    Payal, Rajdeep Singh; Bharath, R; Periyasamy, Ganga; Balasubramanian, S

    2012-01-19

    Density functional theory (DFT) calculations have been carried out for cellobiose and xylan chosen as models for cellulose and hemicellulose, respectively, in gas phase, implicit and explicit solvent (water, methanol, and the ionic liquid, 1,3-dimethylimidazolium acetate) media using plane wave and atom centered basis set approaches in order to find out lowest energy conformers and configurations. Geometry, vibrational properties, and (1)H and (13)C NMR chemical shift values have been discussed under all three conditions. Calculations predict that inter- and intramolecular hydrogen bonding play an important role in the dissolution processes. In the gas phase and in implicit solvent, the anti-anti conformer of cellobiose and the anti-syn conformer of xylan are the most stable due to the formation of a large number of intramolecular hydrogen bonds. However, in the cluster calculations containing ion pairs of the ionic liquid (IL) surrounding the cellulosic units, the anti-syn conformer of cellobiose is more stable as intramolecular hydrogen bonds are substituted by intermolecular ones formed with the ions of the IL. The complexes of cellobiose (or of xylan) with the ions of the ionic liquid are stable with large negative binding energies ranging between -21 and -55 kcal mol(-1). The predicted (1)H NMR values of the lowest energy cellobiose conformers are in good agreement with the experimental value. Xylan binds stronger with the IL than cellobiose does by 20 kcal mol(-1). Furthermore, the two pentose rings in xylan are rotated by 60° to each other in contrast to their coplanarity in cellobiose, which can explain the higher solubility and the amorphous nature of hemicellulose in ionic liquids. The fewer number of hydroxyl groups in xylan (relative to cellobiose) does not affect the number of cations present in its first solvation shell while the number of anions is reduced.

  19. Structures of membrane proteins

    PubMed Central

    Vinothkumar, Kutti R.; Henderson, Richard

    2010-01-01

    In reviewing the structures of membrane proteins determined up to the end of 2009, we present in words and pictures the most informative examples from each family. We group the structures together according to their function and architecture to provide an overview of the major principles and variations on the most common themes. The first structures, determined 20 years ago, were those of naturally abundant proteins with limited conformational variability, and each membrane protein structure determined was a major landmark. With the advent of complete genome sequences and efficient expression systems, there has been an explosion in the rate of membrane protein structure determination, with many classes represented. New structures are published every month and more than 150 unique membrane protein structures have been determined. This review analyses the reasons for this success, discusses the challenges that still lie ahead, and presents a concise summary of the key achievements with illustrated examples selected from each class. PMID:20667175

  20. Rate processes in gas phase

    NASA Technical Reports Server (NTRS)

    Hansen, C. F.

    1983-01-01

    Reaction-rate theory and experiment are given a critical review from the engineers' point of view. Rates of heavy-particle, collision-induced reaction in gas phase are formulated in terms of the cross sections and activation energies for reaction. The effect of cross section function shape and of excited state contributions to reaction both cause the slope of Arrhenius plots to differ from the true activation energy, except at low temperature. The master equations for chemically reacting gases are introduced, and dissociation and ionization reactions are shown to proceed primarily from excited states about kT from the dissociation or ionization limit. Collision-induced vibration, vibration-rotation, and pure rotation transitions are treated, including three-dimensional effects and conservation of energy, which have usually been ignored. The quantum theory of transitions at potential surface crossing is derived, and results are found to be in fair agreement with experiment in spite of some questionable approximations involved.

  1. ¹J(CH) couplings in Group 14/IVA tetramethyls from the gas-phase NMR and DFT structural study: a search for the best computational protocol.

    PubMed

    Nazarski, Ryszard B; Makulski, Włodzimierz

    2014-08-01

    Four tetramethyl compounds EMe4 (E = C, Si, Ge, and Pb) were studied by high-resolution NMR spectroscopy in gaseous and liquid states at 300 K. Extrapolation of experimental vapor-phase C-H J-couplings to a zero-pressure limit permitted determining the (1)J(0,CH)s in methyl groups of their nearly isolated molecules. Theoretical predictions of the latter NMR parameters were also performed in a locally dense basis sets/pseudopotential (Sn, Pb) approach, by applying a few DFT methods pre-selected in calculations of other gas-phase molecular properties of all these species and SnMe4 (bond lengths, C-H stretching IR vibrations). A very good agreement theory vs. experiment was achieved with some computational protocols for all five systems. The trends observed in their geometry and associated coupling constants ((1)J(CH)s, (2)J(HH)s) are discussed and rationalized in terms of the substituent-induced rehybridization of the methyl group (treated as a ligand) carbon, by using Bent's rule and the newly proposed, theoretically derived values of the Mulliken electronegativity (χ) of related atoms and groups. All these χ data for the Group-14/IVA entities were under a lot of controversy for a very long time. As a result, the recommended χ values are semi-experimentally confirmed for the first time and only a small correction is suggested for χ(Ge) and χ(GeMe3).

  2. Quantifying the stabilizing effects of protein–ligand interactions in the gas phase

    PubMed Central

    Allison, Timothy M.; Reading, Eamonn; Liko, Idlir; Baldwin, Andrew J.; Laganowsky, Arthur; Robinson, Carol V.

    2015-01-01

    The effects of protein–ligand interactions on protein stability are typically monitored by a number of established solution-phase assays. Few translate readily to membrane proteins. We have developed an ion-mobility mass spectrometry approach, which discerns ligand binding to both soluble and membrane proteins directly via both changes in mass and ion mobility, and assesses the effects of these interactions on protein stability through measuring resistance to unfolding. Protein unfolding is induced through collisional activation, which causes changes in protein structure and consequently gas-phase mobility. This enables detailed characterization of the ligand-binding effects on the protein with unprecedented sensitivity. Here we describe the method and software required to extract from ion mobility data the parameters that enable a quantitative analysis of individual binding events. This methodology holds great promise for investigating biologically significant interactions between membrane proteins and both drugs and lipids that are recalcitrant to characterization by other means. PMID:26440106

  3. Gas-phase ion isomer analysis reveals the mechanism of peptide sequence scrambling.

    PubMed

    Jia, Chenxi; Wu, Zhe; Lietz, Christopher B; Liang, Zhidan; Cui, Qiang; Li, Lingjun

    2014-03-18

    Peptide sequence scrambling during mass spectrometry-based gas-phase fragmentation analysis causes misidentification of peptides and proteins. Thus, there is a need to develop an efficient approach to probing the gas-phase fragment ion isomers related to sequence scrambling and the underlying fragmentation mechanism, which will facilitate the development of bioinformatics algorithm for proteomics research. Herein, we report on the first use of electron transfer dissociation (ETD)-produced diagnostic fragment ions to probe the components of gas-phase peptide fragment ion isomers. In combination with ion mobility spectrometry (IMS) and formaldehyde labeling, this novel strategy enables qualitative and quantitative analysis of b-type fragment ion isomers. ETD fragmentation produced diagnostic fragment ions indicative of the precursor ion isomer components, and subsequent IMS analysis of b ion isomers provided their quantitative and structural information. The isomer components of three representative b ions (b9, b10, and b33 from three different peptides) were accurately profiled by this method. IMS analysis of the b9 ion isomers exhibited dynamic conversion among these structures. Furthermore, molecular dynamics simulation predicted theoretical drift time values, which were in good agreement with experimentally measured values. Our results strongly support the mechanism of peptide sequence scrambling via b ion cyclization, and provide the first experimental evidence to support that the conversion from molecular precursor ion to cyclic b ion (M → (c)b) pathway is less energetically (or kinetically) favored.

  4. Negative ion gas-phase chemistry of arenes.

    PubMed

    Danikiewicz, Witold; Zimnicka, Magdalena

    2016-01-01

    Reactions of aromatic and heteroaromatic compounds involving anions are of great importance in organic synthesis. Some of these reactions have been studied in the gas phase and are occasionally mentioned in reviews devoted to gas-phase negative ion chemistry, but no reviews exist that collect all existing information about these reactions. This work is intended to fill this gap. In the first part of this review, methods for generating arene anions in the gas phase and studying their physicochemical properties and fragmentation reactions are presented. The main topics in this part are as follows: processes in which gas-phase arene anions are formed, measurements and calculations of the proton affinities of arene anions, proton exchange reactions, and fragmentation processes of substituted arene anions, especially phenide ions. The second part is devoted to gas-phase reactions of arene anions. The most important of these are reactions with electrophiles such as carbonyl compounds and α,β-unsaturated carbonyl and related compounds (Michael acceptors). Other reactions including oxidation of arene anions and halogenophilic reactions are also presented. In the last part of the review, reactions of electrophilic arenes with nucleophiles are discussed. The best known of these is the aromatic nucleophilic substitution (SN Ar) reaction; however, other processes that lead to the substitution of a hydrogen atom in the aromatic ring are also very important. Aromatic substrates in these reactions are usually but not always nitroarenes bearing other substituents in the ring. The first step in these reactions is the formation of an anionic σ-adduct, which, depending on the substituents in the aromatic ring and the structure of the attacking nucleophile, is either an intermediate or a transition state in the reaction path. In the present review, we attempted to collect the results of both experimental and computational studies of the aforementioned reactions conducted since the

  5. Protein Structure Databases.

    PubMed

    Laskowski, Roman A

    2016-01-01

    Web-based protein structure databases come in a wide variety of types and levels of information content. Those having the most general interest are the various atlases that describe each experimentally determined protein structure and provide useful links, analyses, and schematic diagrams relating to its 3D structure and biological function. Also of great interest are the databases that classify 3D structures by their folds as these can reveal evolutionary relationships which may be hard to detect from sequence comparison alone. Related to these are the numerous servers that compare folds-particularly useful for newly solved structures, and especially those of unknown function. Beyond these are a vast number of databases for the more specialized user, dealing with specific families, diseases, structural features, and so on. PMID:27115626

  6. Densonucleosis virus structural proteins.

    PubMed

    Kelly, D C; Moore, N F; Spilling, C R; Barwise, A H; Walker, I O

    1980-10-01

    The protein coats of two densonucleosis viruses (types 1 and 2) were examined by a variety of biophysical, biochemical, and serological techniques. The viruses were 24 nm in diameter, contained at least four polypeptides, were remarkably stable to extremes of pH and denaturing agents, and were serologically closely related. The two viruses could, however, be distinguished serologically and by differences in migration of their structural polypeptides. For each virus the "top component" (i.e., the protein coat minus DNA, found occurring naturally in infections) appeared to have a composition identical to that of the coat of the virus and was a more stable structure. Electrometric titration curves of the virus particles and top components demonstrated that the DNA phosphate in densonucleosis virus particles was neutralized by cations other than basic amino acid side chains of the protein coat. Circular dichroism studies showed that there was a conformational difference between the protein coats of top components and virus particles.

  7. Junin virus structural proteins.

    PubMed Central

    De Martínez Segovia, Z M; De Mitri, M I

    1977-01-01

    Polyacrylamide gel electrophoresis of purified Junin virus revealed six distinct structural polypeptides, two major and four minor ones. Four of these polypeptides appeared to be covalently linked with carbohydrate. The molecular weights of the six proteins, estimated by coelectrophoresis with marker proteins, ranged from 25,000 to 91,000. One of the two major components (number 3) was identified as a nucleoprotein and had a molecular weight of 64,000. It was the most prominent protein and was nonglycosylated. The other major protein (number 5), with a molecular weight of 38,000, was a glucoprotein and a component of the viral envelope. The location on the virion of three additional glycopeptides with molecular weights of 91,000, 72,000, and 52,000, together with a protein with a molecular weight of 25,000, was not well defined. PMID:189088

  8. Hydrated metal ions in the gas phase.

    PubMed

    Beyer, Martin K

    2007-01-01

    Studying metal ion solvation, especially hydration, in the gas phase has developed into a field that is dominated by a tight interaction between experiment and theory. Since the studied species carry charge, mass spectrometry is an indispensable tool in all experiments. Whereas gas-phase coordination chemistry and reactions of bare metal ions are reasonably well understood, systems containing a larger number of solvent molecules are still difficult to understand. This review focuses on the rich chemistry of hydrated metal ions in the gas phase, covering coordination chemistry, charge separation in multiply charged systems, as well as intracluster and ion-molecule reactions. Key ideas of metal ion solvation in the gas phase are illustrated with rare-gas solvated metal ions.

  9. Probing The Electronic Structure of Fe-S Clusters: Ubiquitous Electron Transfer Centers in Metalloproteins Using Anion Photoelectron Spectroscopy in the Gas Phase

    SciTech Connect

    Yang, Xin; Wang, Xue B.; FU, You-Jun; Wang, Lai S.

    2006-10-06

    Iron-Sulfur clusters are found in all forms of life, which constitute the active sites of a growing list of proteins in such essential life-sustaining processes as respiration, nitrogen fixation, and photosynthesis (Spiro 1982). The most prototypical and ubiquitous Fe-S cluster is the cubane-type [4Fe-4S] cluster, which, in addition to its catalytic and regulatory roles, appears to be nature’s favorite agent for electron transfer and storage, such as in ferrodoxins (Fds), high-potential iron proteins (HiPIPs), and the integral machineries of hydrogenases and nitrogenases (Bernnert et al. 1997; Einsle etal. 2002; Peters et al. 1998). In proteins, the cubane [4Fe-4S] unit is usually coordinated by the amino acid cysteine. The [4Fe-4S] core functions as electron transfer agent usually between the following oxidation states: [4Fe-4S]1+ ↔ [4Fe-4S]2+ ↔ [4Fe-4S]3+ . A fourth state, the all-ferrous species [4Fe-4S]0, was also detected in the iron protein of nitrogenase.

  10. Solvation-induced σ-complex structure formation in the gas phase: a revisit to the infrared spectroscopy of [C6H6-(CH3OH)2]+.

    PubMed

    Mizuse, Kenta; Suzuki, Yuta; Mikami, Naohiko; Fujii, Asuka

    2011-10-20

    Structures of the [C(6)H(6)-(CH(3)OH)(2)](+) cluster cation are investigated with infrared (IR) spectroscopy. While the noncovalent type structure has been confirmed for the n = 1 cluster of [C(6)H(6)-(CH(3)OH)(n)](+), only contradictory interpretations have been given for the spectra of n = 2, in which significant changes have been observed with the Ar tagging. In the present study, we revisit IR spectroscopy of the n = 2 cluster from the viewpoint of the σ-complex structure, which includes a covalent bond formation between the benzene and methanol moieties. The observed spectral range is extended to the lower-frequency region, and the spectrum is measured with and without Ar and N(2) tagging. A strongly hydrogen-bonded OH stretch band, which is characteristic to the σ-complex structure, is newly found with the tagging. The remarkable spectral changes with the tagging are interpreted by the competition between the σ-complex and noncovalent complex structures in the [C(6)H(6)-(CH(3)OH)(2)](+) system. This result shows that the microsolvation only with one methanol molecule can induce the σ-complex structure formation.

  11. Inductive and steric effects on the gas-phase structure of tert-butyl acetate. Electron diffraction and ab initio MO investigations

    SciTech Connect

    Takeuchi, Hiroshi; Enmi, Jun-ichiro; Onozaki, Manabu; Egawa, Toru; Konaka, Shigehiro

    1994-09-01

    Gas electron diffusion and HF/4-21 G calculations on geometric parameters and harmonic force constants are used to study the molecular structure of tert-butyl acetate. This determined that C{sub 1} = O{sub 2} is (cis) to O{sub 4}-C{sub 5} and the tert-butyl group is staggered to the C{sub 1}-O{sub 4} bond. The structural parameters are also determined. C{sub 1}-O{sub 4} bond length shortening is rationalized in terms of the resonance effect and the electron-releasing inductive effect of substituents. 29 refs., 4 figs., 4 tabs.

  12. Structure and mechanism of the formation of core-shell nanoparticles obtained through a one-step gas-phase synthesis by electron beam evaporation.

    PubMed

    Nomoev, Andrey V; Bardakhanov, Sergey P; Schreiber, Makoto; Bazarova, Dashima G; Romanov, Nikolai A; Baldanov, Boris B; Radnaev, Bair R; Syzrantsev, Viacheslav V

    2015-01-01

    The structure of core-shell Cu@silica and Ag@Si nanoparticles obtained in one-step through evaporation of elemental precursors by a high-powered electron beam are investigated. The structure of the core and shell of the particles are investigated in order to elucidate their mechanisms of formation and factors affecting the synthesis. It is proposed that the formation of Cu@silica particles is mainly driven by surface tension differences between Cu and Si while the formation of Ag@Si particles is mainly driven by differences in the vapour concentration of the two components.

  13. The gas-phase structure of 1-selena-closo-dodecaborane(11), 1-SeB11H11, determined by the concerted use of electron diffraction and computational methods.

    PubMed

    Hnyk, Drahomír; Wann, Derek A; Holub, Josef; Bühl, Michael; Robertson, Heather E; Rankin, David W H

    2008-01-01

    The molecular structure of 1-selena-closo-dodecaborane(11), 1-SeB11H11, has been determined by the concerted use of quantum chemical calculations and gas-phase electron diffraction. The structure has C(5v) symmetry and is distorted from a regular icosahedron mainly through the expansion of the pentagon of boron atoms adjacent to selenium, with r(a3,1)(B-B) = 192.2(2) pm. The Se-B bond length is extremely well determined [r(a3,1) (Se-B) = 212.9(2) pm] and this is reflected by a pronounced peak in the radial-distribution curve. The accuracy of the experimental structure, as well as that calculated at the MP2/962(d) level, has been gauged by comparison of the 11B chemical shifts (calculated at two different gauge-including atomic orbitals (GIAO) levels) with experimental NMR values. The inclusion of electron correlation in the magnetic property calculations (GIAO-MP2) gave superior results to those carried out using GIAO-Hartree-Fock.

  14. Experimental observation of structures with subtle balance between strong hydrogen bond and weak n → π(*) interaction: Gas phase laser spectroscopy of 7-azaindole⋯fluorosubstituted pyridines.

    PubMed

    Singh, Santosh K; Vaishnav, Jamuna K; Das, Aloke

    2016-09-14

    In this study, interplay between a strong hydrogen bond and a very weak n → π(*) interaction has been probed through experiment for the first time. We have used resonant 2-photon ionization, Infrared-ultraviolet double resonance spectroscopy, and quantum chemistry calculation to determine the structures of 7-azaindole⋯2,6-difluoropyridine and 7-azaindole⋯2,3,5,6-tetrafluororpyridine complexes, which are stabilized by both hydrogen bonding and n → π(*) interaction. The structures of the complexes studied in the present work have been compared with the double hydrogen bonded (N-H⋯N and C-H⋯N) planar structure of 7-azaindole⋯2-fluoropyridine. It has been found that the strength of the N-H⋯N hydrogen bond in the 7-azaindole⋯2,6-substituted fluoropyridines is affected due to several factors. The main reason for huge reduction in the strength of this N-H⋯N hydrogen bond in these complexes is due to loss of the C-H⋯N hydrogen bond, through substitution of fluorine atoms in 2 and 6 positions, which induces major structural changes by bending the hydrogen bond and introducing the n → π(*) interaction. Effect of fluorination as well as presence of the n → π(*) interaction in these complexes also contributes to the reduction of the strength of the N-H⋯N interaction. Although it is difficult to quantify the role of the n → π(*) interaction to affect the strength of the hydrogen bond, observation of the structures, where a strong hydrogen bond and a weak n → π(*) interaction co-exist, is confirmed. PMID:27634255

  15. Experimental observation of structures with subtle balance between strong hydrogen bond and weak n → π* interaction: Gas phase laser spectroscopy of 7-azaindole⋯fluorosubstituted pyridines

    NASA Astrophysics Data System (ADS)

    Singh, Santosh K.; Vaishnav, Jamuna K.; Das, Aloke

    2016-09-01

    In this study, interplay between a strong hydrogen bond and a very weak n → π* interaction has been probed through experiment for the first time. We have used resonant 2-photon ionization, Infrared-ultraviolet double resonance spectroscopy, and quantum chemistry calculation to determine the structures of 7-azaindole⋯2,6-difluoropyridine and 7-azaindole⋯2,3,5,6-tetrafluororpyridine complexes, which are stabilized by both hydrogen bonding and n → π* interaction. The structures of the complexes studied in the present work have been compared with the double hydrogen bonded (N-H⋯N and C-H⋯N) planar structure of 7-azaindole⋯2-fluoropyridine. It has been found that the strength of the N-H⋯N hydrogen bond in the 7-azaindole⋯2,6-substituted fluoropyridines is affected due to several factors. The main reason for huge reduction in the strength of this N-H⋯N hydrogen bond in these complexes is due to loss of the C-H⋯N hydrogen bond, through substitution of fluorine atoms in 2 and 6 positions, which induces major structural changes by bending the hydrogen bond and introducing the n → π* interaction. Effect of fluorination as well as presence of the n → π* interaction in these complexes also contributes to the reduction of the strength of the N-H⋯N interaction. Although it is difficult to quantify the role of the n → π* interaction to affect the strength of the hydrogen bond, observation of the structures, where a strong hydrogen bond and a weak n → π* interaction co-exist, is confirmed.

  16. Intramolecular structure and dynamics of mequinol and guaiacol in the gas phase: Rotationally resolved electronic spectra of their S{sub 1} states

    SciTech Connect

    Ruiz-Santoyo, José Arturo; Rodríguez-Matus, Marcela; Álvarez-Valtierra, Leonardo E-mail: gmerino@mda.cinvestav.mx; Cabellos, José Luis; Merino, Gabriel E-mail: gmerino@mda.cinvestav.mx; Yi, John T.; Pratt, David W.; Schmitt, Michael

    2015-09-07

    The molecular structures of guaiacol (2-methoxyphenol) and mequinol (4-methoxyphenol) have been studied using high resolution electronic spectroscopy in a molecular beam and contrasted with ab initio computations. Mequinol exhibits two low frequency bands that have been assigned to electronic origins of two possible conformers of the molecule, trans and cis. Guaiacol also shows low frequency bands, but in this case, the bands have been assigned to the electronic origin and vibrational modes of a single conformer of the isolated molecule. A detailed study of these bands indicates that guaiacol has a vibrationally averaged planar structure in the ground state, but it is distorted along both in-plane and out-of-plane coordinates in the first electronically excited state. An intramolecular hydrogen bond involving the adjacent   –OH and   –OCH{sub 3} groups plays a major role in these dynamics.

  17. Measuring Complementary Electronic Structure Properties of both Deposited and Gas Phase Clusters using STM, UPS, and PES: Size-Selected Clusters on Surfaces

    SciTech Connect

    Bowen, Kit H.

    2014-03-05

    In this project, we studied size-selected cluster interactions with surfaces, with other clusters on surfaces, and with external stimuli. These studies focused on mobility as a function of cluster size, surface morphologies as a function of composition and coverage, ion-induced modification and reactivity of clusters as a function of composition, the structural evolution of cluster cuboids culminating in the characterization of theoretically-predicted “baby crystal” clusters, and unusual fractal pattern formation due to deposition.

  18. Structures of [M(Ura-H)(H2 O)n ](+) (M = Mg, Ca, Sr, Ba; n = 1-3) complexes in the gas phase by IRMPD spectroscopy and theoretical studies.

    PubMed

    Power, Barry; Haldys, Violette; Salpin, Jean-Yves; Fridgen, Travis D

    2016-03-01

    The structures of singly and doubly (and for Mg, triply) hydrated group 2 metal dications bound to deprotonated uracil were explored in the gas phase using infrared multiple photon dissociation spectroscopy in the mid-infrared region (1000-1900 cm(-1) ) and the O-H/N-H stretching region (2700-3800 cm(-1) ) in a Fourier transform ion cyclotron resonance mass spectrometer. The infrared multiple photon dissociation spectra were then compared with the computed IR spectra for various isomers. Calculations were performed using B3LYP with the 6-31 + G(d,p) basis set for all atoms except Ba(2+) and Sr(2+) , for which the LANL2DZ or the def2-TZVPP basis sets with relativistic core potentials were used. Atoms-in-molecules analysis was conducted for all lowest energy structures. The lowest energy isomers in all cases are those in which the one uracil is deprotonated at the N3 position, and the metal is coordinated to the N3 and O4 of uracil. Regardless of the degree of solvation, all water molecules are bound to the metal ion and participate in a hydrogen bond with a carbonyl of the uracil moiety.

  19. Structures of [M(Ura-H)(H2 O)n ](+) (M = Mg, Ca, Sr, Ba; n = 1-3) complexes in the gas phase by IRMPD spectroscopy and theoretical studies.

    PubMed

    Power, Barry; Haldys, Violette; Salpin, Jean-Yves; Fridgen, Travis D

    2016-03-01

    The structures of singly and doubly (and for Mg, triply) hydrated group 2 metal dications bound to deprotonated uracil were explored in the gas phase using infrared multiple photon dissociation spectroscopy in the mid-infrared region (1000-1900 cm(-1) ) and the O-H/N-H stretching region (2700-3800 cm(-1) ) in a Fourier transform ion cyclotron resonance mass spectrometer. The infrared multiple photon dissociation spectra were then compared with the computed IR spectra for various isomers. Calculations were performed using B3LYP with the 6-31 + G(d,p) basis set for all atoms except Ba(2+) and Sr(2+) , for which the LANL2DZ or the def2-TZVPP basis sets with relativistic core potentials were used. Atoms-in-molecules analysis was conducted for all lowest energy structures. The lowest energy isomers in all cases are those in which the one uracil is deprotonated at the N3 position, and the metal is coordinated to the N3 and O4 of uracil. Regardless of the degree of solvation, all water molecules are bound to the metal ion and participate in a hydrogen bond with a carbonyl of the uracil moiety. PMID:26956390

  20. Photoionization of cold gas phase coronene and its clusters: Autoionization resonances in monomer, dimer, and trimer and electronic structure of monomer cation

    NASA Astrophysics Data System (ADS)

    Bréchignac, Philippe; Garcia, Gustavo A.; Falvo, Cyril; Joblin, Christine; Kokkin, Damian; Bonnamy, Anthony; Parneix, Pascal; Pino, Thomas; Pirali, Olivier; Mulas, Giacomo; Nahon, Laurent

    2014-10-01

    Polycyclic aromatic hydrocarbons (PAHs) are key species encountered in a large variety of environments such as the Interstellar Medium (ISM) and in combustion media. Their UV spectroscopy and photodynamics in neutral and cationic forms are important to investigate in order to learn about their structure, formation mechanisms, and reactivity. Here, we report an experimental photoelectron-photoion coincidence study of a prototypical PAH molecule, coronene, and its small clusters, in a molecular beam using the vacuum ultraviolet (VUV) photons provided by the SOLEIL synchrotron facility. Mass-selected high resolution threshold photoelectron (TPES) and total ion yield spectra were obtained and analyzed in detail. Intense series of autoionizing resonances have been characterized as originating from the monomer, dimer, and trimer neutral species, which may be used as spectral fingerprints for their detection in the ISM by VUV absorption spectroscopy. Finally, a full description of the electronic structure of the monomer cation was made and discussed in detail in relation to previous spectroscopic optical absorption data. Tentative vibrational assignments in the near-threshold TPES spectrum of the monomer have been made with the support of a theoretical approach based on density functional theory.

  1. Ab initio structural and spectroscopic study of HPS{sup x} and HSP{sup x} (x = 0,+1,−1) in the gas phase

    SciTech Connect

    Yaghlane, Saida Ben; Cotton, C. Eric; Francisco, Joseph S. E-mail: hochlaf@univ-mlv.fr; Linguerri, Roberto; Hochlaf, Majdi E-mail: hochlaf@univ-mlv.fr

    2013-11-07

    Accurate ab initio computations of structural and spectroscopic parameters for the HPS/HSP molecules and corresponding cations and anions have been performed. For the electronic structure computations, standard and explicitly correlated coupled cluster techniques in conjunction with large basis sets have been adopted. In particular, we present equilibrium geometries, rotational constants, harmonic vibrational frequencies, adiabatic ionization energies, electron affinities, and, for the neutral species, singlet-triplet relative energies. Besides, the full-dimensional potential energy surfaces (PESs) for HPS{sup x} and HSP{sup x} (x = −1,0,1) systems have been generated at the standard coupled cluster level with a basis set of augmented quintuple-zeta quality. By applying perturbation theory to the calculated PESs, an extended set of spectroscopic constants, including τ, first-order centrifugal distortion and anharmonic vibrational constants has been obtained. In addition, the potentials have been used in a variational approach to deduce the whole pattern of vibrational levels up to 4000 cm{sup −1} above the minima of the corresponding PESs.

  2. Photoionization of cold gas phase coronene and its clusters: Autoionization resonances in monomer, dimer, and trimer and electronic structure of monomer cation

    SciTech Connect

    Bréchignac, Philippe Falvo, Cyril; Parneix, Pascal; Pino, Thomas; Pirali, Olivier; Garcia, Gustavo A.; Nahon, Laurent; Joblin, Christine; Kokkin, Damian; Bonnamy, Anthony; Mulas, Giacomo

    2014-10-28

    Polycyclic aromatic hydrocarbons (PAHs) are key species encountered in a large variety of environments such as the Interstellar Medium (ISM) and in combustion media. Their UV spectroscopy and photodynamics in neutral and cationic forms are important to investigate in order to learn about their structure, formation mechanisms, and reactivity. Here, we report an experimental photoelectron-photoion coincidence study of a prototypical PAH molecule, coronene, and its small clusters, in a molecular beam using the vacuum ultraviolet (VUV) photons provided by the SOLEIL synchrotron facility. Mass-selected high resolution threshold photoelectron (TPES) and total ion yield spectra were obtained and analyzed in detail. Intense series of autoionizing resonances have been characterized as originating from the monomer, dimer, and trimer neutral species, which may be used as spectral fingerprints for their detection in the ISM by VUV absorption spectroscopy. Finally, a full description of the electronic structure of the monomer cation was made and discussed in detail in relation to previous spectroscopic optical absorption data. Tentative vibrational assignments in the near-threshold TPES spectrum of the monomer have been made with the support of a theoretical approach based on density functional theory.

  3. Broadband Microwave Spectroscopy as a Tool to Study the Structures of Odorant Molecules and Weakly Bound Complexes in the Gas Phase

    NASA Astrophysics Data System (ADS)

    Zinn, Sabrina; Betz, Thomas; Medcraft, Chris; Schnell, Melanie

    2015-06-01

    The rotational spectrum of trans-cinnamaldehyde ((2E)-3-phenylprop-2-enal) has been obtained with chirped-pulse microwave spectroscopy in the frequency range of 2 - 8.5 GHz. The odorant molecule is the essential component in cinnamon oil and causes the characteristic smell. In the measured high-resolution spectrum, we were able to assign the rotational spectra of two conformers of trans-cinnamaldehyde as well as all singly 13C-substituted species of the lowest-energy conformer in natural abundance. Two different methods were used to determine the structure from the rotational constants, which will be compared within this contribution. In addition, the current progress of studying ether-alcohol complexes, aiming at an improved understanding of the interplay between hydrogen bonding and dispersion interaction, will be reported. Here, a special focus is placed on the complexes of diphenylether with small aliphatic alcohols.

  4. Vibrational spectra and gas-phase structure of N-methyl-S,S-bis(trifluoromethyl)sulfimide, CH3N=S(CF3)2.

    PubMed

    Trautner, Frank; Alvarez, Rosa M S; Cutin, Edgardo H; Robles, Norma L; Mews, Rüdiger; Oberhammer, Heinz

    2005-10-17

    The molecular structure of N-methyl-S,S-bis(trifluoromethyl)sulfimide, CH3N=S(CF3)2, was determined by gas electron diffraction and quantum chemical calculations [B3LYP and MP2 with 6-31+G(2df,p) basis sets]. Furthermore, vibrational spectra, IR (gas) and Raman (liquid), were recorded. These spectra were assigned by comparison with analogous molecules and with calculated frequencies and intensities (HF, B3LYP, and MP2 with 6-311G basis sets). All experimental data and computational methods result in a single conformer with syn orientation of the CH3 group relative to the bisector of the two CF3 groups. The molecule possesses C1 symmetry, slightly distorted from CS symmetry. The N=S bond length in this compound [1.522(10) A] is longer than that in imidosulfur difluorides RN=SF2 [1.476(4) A - 1.487(5) A].

  5. Synthesis, structure and gas-phase reactivity of the mixed silver hydride borohydride nanocluster [Ag3(μ3-H)(μ3-BH4)L(Ph)3]BF4 (L(Ph) = bis(diphenylphosphino)methane).

    PubMed

    Zavras, Athanasios; Ariafard, Alireza; Khairallah, George N; White, Jonathan M; Mulder, Roger J; Canty, Allan J; O'Hair, Richard A J

    2015-11-21

    Borohydrides react with silver salts to give products that span multiple scales ranging from discrete mononuclear compounds through to silver nanoparticles and colloids. The cluster cations [Ag3(H)(BH4)L3](+) are observed upon electrospray ionization mass spectrometry of solutions containing sodium borohydride, silver(I) tetrafluoroborate and bis(dimethylphosphino)methane (L(Me)) or bis(diphenylphosphino)methane (L(Ph)). By adding NaBH4 to an acetonitrile solution of AgBF4 and L(Ph), cooled to ca. -10 °C, we have been able to isolate the first mixed silver hydride borohydride nanocluster, [Ag3(μ3-H)(μ3-BH4)L(Ph)3]BF4, and structurally characterise it via X-ray crystallography. Combined gas-phase experiments (L(Me) and L(Ph)) and DFT calculations (L(Me)) reveal how loss of a ligand from the cationic complexes [Ag3(H)(BH4)L3](+) provides a change in geometry that facilitates subsequent loss of BH3 to produce the dihydride clusters, [Ag3(H)2Ln](+) (n = 1 and 2). Together with the results of previous studies (Girod et al., Chem. - Eur. J., 2014, 20, 16626), this provides a direct link between mixed silver hydride/borohydride nanoclusters, silver hydride nanoclusters, and silver nanoclusters.

  6. The physical chemistry of Criegee intermediates in the gas phase

    SciTech Connect

    Osborn, David L.; Taatjes, Craig A.

    2015-07-24

    Here, carbonyl oxides, also known as Criegee intermediates, are key intermediates in both gas phase ozonolysis of unsaturated hydrocarbons in the troposphere and solution phase organic synthesis via ozonolysis. Although the study of Criegee intermediates in both arenas has a long history, direct studies in the gas phase have only recently become possible through new methods of generating stabilised Criegee intermediates in sufficient quantities. This advance has catalysed a large number of new experimental and theoretical investigations of Criegee intermediate chemistry. In this article we review the physical chemistry of Criegee intermediates, focusing on their molecular structure, spectroscopy, unimolecular and bimolecular reactions. These recent results have overturned conclusions from some previous studies, while confirming others, and have clarified areas of investigation that will be critical targets for future studies. In addition to expanding our fundamental understanding of Criegee intermediates, the rapidly expanding knowledge base will support increasingly predictive models of their impacts on society.

  7. The physical chemistry of Criegee intermediates in the gas phase

    DOE PAGESBeta

    Osborn, David L.; Taatjes, Craig A.

    2015-07-24

    Here, carbonyl oxides, also known as Criegee intermediates, are key intermediates in both gas phase ozonolysis of unsaturated hydrocarbons in the troposphere and solution phase organic synthesis via ozonolysis. Although the study of Criegee intermediates in both arenas has a long history, direct studies in the gas phase have only recently become possible through new methods of generating stabilised Criegee intermediates in sufficient quantities. This advance has catalysed a large number of new experimental and theoretical investigations of Criegee intermediate chemistry. In this article we review the physical chemistry of Criegee intermediates, focusing on their molecular structure, spectroscopy, unimolecular andmore » bimolecular reactions. These recent results have overturned conclusions from some previous studies, while confirming others, and have clarified areas of investigation that will be critical targets for future studies. In addition to expanding our fundamental understanding of Criegee intermediates, the rapidly expanding knowledge base will support increasingly predictive models of their impacts on society.« less

  8. On the interplay between geometrical structure and magnetic anisotropy: a relativistic density-functional study of mixed Pt-Co and Pt-Fe trimers and tetramers in the gas-phase and supported on graphene.

    PubMed

    Błoński, Piotr; Hafner, Jürgen

    2015-02-01

    The structural and magnetic properties of mixed Pt-Co and Pt-Fe trimers and tetramers in the gas-phase and supported on a free-standing graphene layer have been calculated using density-functional theory. The influence of the strong magnetic moments of the 3d atoms on the Pt atoms and the influence of the strong spin-orbit coupling contributed by the Pt atoms on the 3d atoms have been studied in detail. All mixed trimers form isocele triangles in the gas-phase. On a graphene layer the structure is influenced by the strong binding of the 3d atoms, leading to an asymmetric configuration for Pt-rich and more symmetric structures for 3d-rich clusters. The magnetic anisotropy energy defined as the energy difference for easy and hard magnetization directions varies between 5 and 13 meV/atom for the free trimers, but is strongly reduced to values between 0.7 and 6.6 meV/atom for the graphene-supported clusters. The saddle-point energy representing the barrier against magnetization reversal is on average 3 meV/atom for free trimers, it is reduced to 2 meV/atom for the more symmetric PtCo(Fe)(2) clusters, and to only about 0.3 meV/atom for the asymmetric Pt(2)Co(Fe) cluster on graphene. For the mixed tetramers the strong magnetism stabilizes a flat geometric structure, except for Pt(3)Co which forms a distorted trigonal pyramid. The geometry of the graphene-supported tetramers is very different due to the requirement of a good match to the substrate. Large magnetic anisotropy energies are found for free Pt(3)Co where the change of the magnetization direction also induces a transition from a high- to a low-moment magnetic isomer. For all other free tetramers the magnetic anisotropy energy ranges between 3 to 5 meV/atom only, it is further reduced to 0.4 to 3.8 meV/atom for the graphene-supported tetramers. The reduction is strongest for Pt(3)Fe/graphene because of the asymmetric structure of the adsorption complex. The barriers against magnetization reversal range between

  9. Continuous-Flow Gas-Phase Bioreactors

    NASA Technical Reports Server (NTRS)

    Wise, Donald L.; Trantolo, Debra J.

    1994-01-01

    Continuous-flow gas-phase bioreactors proposed for biochemical, food-processing, and related industries. Reactor contains one or more selected enzymes dehydrated or otherwise immobilized on solid carrier. Selected reactant gases fed into reactor, wherein chemical reactions catalyzed by enzyme(s) yield product biochemicals. Concept based on discovery that enzymes not necessarily placed in traditional aqueous environments to function as biocatalysts.

  10. EPA GAS PHASE CHEMISTRY CHAMBER STUDIES

    EPA Science Inventory

    Gas-phase smog chamber experiments are being performed at EPA in order to evaluate a number of current chemical mechanisms for inclusion in EPA regulatory and research models. The smog chambers are 9000 L in volume and constructed of 2-mil teflon film. One of the chambers is co...

  11. Gas-Phase Infrared; JCAMP Format

    National Institute of Standards and Technology Data Gateway

    SRD 35 NIST/EPA Gas-Phase Infrared; JCAMP Format (PC database for purchase)   This data collection contains 5,228 infrared spectra in the JCAMP-DX (Joint Committee for Atomic and Molecular Physical Data "Data Exchange") format.

  12. Fundamental thermochemical properties of amino acids: gas-phase and aqueous acidities and gas-phase heats of formation.

    PubMed

    Stover, Michele L; Jackson, Virgil E; Matus, Myrna H; Adams, Margaret A; Cassady, Carolyn J; Dixon, David A

    2012-03-01

    The gas-phase acidities of the 20 L-amino acids have been predicted at the composite G3(MP2) level. A broad range of structures of the neutral and anion were studied to determine the lowest energy conformer. Excellent agreement is found with the available experimental gas-phase deprotonation enthalpies, and the calculated values are within experimental error. We predict that tyrosine is deprotonated at the CO(2)H site. Cysteine is predicted to be deprotonated at the SH but the proton on the CO(2)H is shared with the S(-) site. Self-consistent reaction field (SCRF) calculations with the COSMO parametrization were used to predict the pK(a)'s of the non-zwitterion form in aqueous solution. The differences in the non-zwitterion pK(a) values were used to estimate the free energy difference between the zwitterion and nonzwitterion forms in solution. The heats of formation of the neutral compounds were calculated from atomization energies and isodesmic reactions to provide the first reliable set of these values in the gas phase. Further calculations were performed on five rare amino acids to predict their heats of formation, acidities, and pK(a) values.

  13. Experimental Thermochemistry of Gas Phase Cytosine Tautomers

    NASA Astrophysics Data System (ADS)

    Morrison, A. M.; Douberly, G. E.

    2011-06-01

    Enthalpies of interconversion are measured for the three lowest energy tautomers of isolated cytosine. The equilibrium distribution of tautomers near 600 K is frozen upon the capture of the gas phase species by low temperature helium nanodroplets. The temperature dependence of the gas phase cytosine tautomer populations is determined with infrared laser spectroscopy of the helium solvated species. The interconverison enthalpies obtained from the van't Hoff relation are 1.14 ± 0.21 and 1.63 ± 0.12 for the C31 rightleftharpoons C32 and C31 rightleftharpoons C1 equilibria, respectively. C31 and C32 are rotamers of an enol tautomer, and C1 is a keto tautomer. The interconversion enthalpies are compared to recent CCSD(T) thermochemistry calculations of cytosine tautomers.

  14. Gas phase chemistry of chlorine nitrate

    SciTech Connect

    Okumura, M.; Moore, T.A.; Crellin, K.C.

    1995-12-31

    Chlorine nitrate (ClONO{sub 2}) is a reservoir of both ClO{sub x} and NO{sub x} radicals in Earth`s stratosphere, and its decomposition is important in determining the abundance of stratospheric ozone. We present experimental and theoretical studies that explore the mechanisms and dynamics of processes leading to ClONO{sub 2} destruction in the stratosphere. Molecular beam photodissociation experiments have been performed to determine the decomposition pathways of ClONO{sub 2} upon excitation at 308 nm and to explore the possibility of a long-lived excited state. We have also investigated the reaction of chlorine nitrate with chloride ions Cl{sup -} in the gas phase. The gas phase ionic reaction may elucidate ionic mechanisms of heterogeneous reactions occurring on the surfaces of Polar Stratospheric Cloud particles and also raise doubts about proposed schemes to mitigate ozone depletion by electrifying the stratosphere.

  15. How to select gas-phase filters

    SciTech Connect

    Groeger, G.; Winters, P.

    1997-10-01

    Removing airborne molecular contamination (AMC) from indoor industrial air is a challenging problem. Under OSHA, companies must mitigate harmful effects from corrosive, acid and alkaline gases to protect employee health. Equally important, corrosive gases tremendously impact and compromise operation of sensitive plant instrumentation and process control devices. Gases such as SO{sub 2}, H{sub 2}S, VOCs, etc., are present in many manufacturing facilities. These contaminants can be controlled to tolerable levels with gas-phase filtration techniques. Because each manufacturing facility has its own unique problem, a one-size-fits-all-solution is not possible. The presented examples and laboratory data evaluate several gas-phase control technologies under varying contaminant concentrations and air stream velocities. Using this information, engineers can find the best solution for their AMC problem.

  16. Gas-Phase Molecular Dynamics: High Resolution Spectroscopy and Collision Dynamics of Transient Species

    SciTech Connect

    Hall,G.E.; Sears, T.J.

    2009-04-03

    This research is carried out as part of the Gas-Phase Molecular Dynamics program in the Chemistry Department at Brookhaven National Laboratory. High-resolution spectroscopy, augmented by theoretical and computational methods, is used to investigate the structure and collision dynamics of chemical intermediates in the elementary gas-phase reactions involved in combustion chemistry. Applications and methods development are equally important experimental components of this work.

  17. Structural Genomics of Protein Phosphatases

    SciTech Connect

    Almo,S.; Bonanno, J.; Sauder, J.; Emtage, S.; Dilorenzo, T.; Malashkevich, V.; Wasserman, S.; Swaminathan, S.; Eswaramoorthy, S.; et al

    2007-01-01

    The New York SGX Research Center for Structural Genomics (NYSGXRC) of the NIGMS Protein Structure Initiative (PSI) has applied its high-throughput X-ray crystallographic structure determination platform to systematic studies of all human protein phosphatases and protein phosphatases from biomedically-relevant pathogens. To date, the NYSGXRC has determined structures of 21 distinct protein phosphatases: 14 from human, 2 from mouse, 2 from the pathogen Toxoplasma gondii, 1 from Trypanosoma brucei, the parasite responsible for African sleeping sickness, and 2 from the principal mosquito vector of malaria in Africa, Anopheles gambiae. These structures provide insights into both normal and pathophysiologic processes, including transcriptional regulation, regulation of major signaling pathways, neural development, and type 1 diabetes. In conjunction with the contributions of other international structural genomics consortia, these efforts promise to provide an unprecedented database and materials repository for structure-guided experimental and computational discovery of inhibitors for all classes of protein phosphatases.

  18. Protein structure modeling with MODELLER.

    PubMed

    Webb, Benjamin; Sali, Andrej

    2014-01-01

    Genome sequencing projects have resulted in a rapid increase in the number of known protein sequences. In contrast, only about one-hundredth of these sequences have been characterized at atomic resolution using experimental structure determination methods. Computational protein structure modeling techniques have the potential to bridge this sequence-structure gap. In this chapter, we present an example that illustrates the use of MODELLER to construct a comparative model for a protein with unknown structure. Automation of a similar protocol has resulted in models of useful accuracy for domains in more than half of all known protein sequences.

  19. Star formation and gas phase history of the cosmic web

    NASA Astrophysics Data System (ADS)

    Snedden, Ali; Coughlin, Jared; Phillips, Lara Arielle; Mathews, Grant; Suh, In-Saeng

    2016-01-01

    We present a new method of tracking and characterizing the environment in which galaxies and their associated circumgalactic medium evolve. We have developed a structure finding algorithm that uses the rate of change of the density gradient to self-consistently parse and follow the evolution of groups/clusters, filaments and voids in large-scale structure simulations. We use this to trace the complete evolution of the baryons in the gas phase and the star formation history within each structure in our simulated volume. We vary the structure measure threshold to probe the complex inner structure of star-forming regions in poor clusters, filaments and voids. We find that the majority of star formation occurs in cold, condensed gas in filaments at intermediate redshifts (z ˜ 3). We also show that much of the star formation above a redshift z = 3 occurs in low-contrast regions of filaments, but as the density contrast increases at lower redshift, star formation switches to the high-contrast regions, or inner parts, of filaments. Since filaments bridge the void and cluster regions, it suggests that the majority of star formation occurs in galaxies in intermediate density regions prior to the accretion on to groups/clusters. We find that both filaments and poor clusters are multiphase environments distinguishing themselves by different distributions of gas phases.

  20. Gas phase thermochemistry of organogermanium compounds

    SciTech Connect

    Engel, J.P.

    1993-12-07

    A variety of silyl- and alkyl-germylene precursors have been synthesized and subsequently pyrolyzed in the gas phase. Arrhenius parameters were obtained employing a pulsed-stirred flow reactor for these unimolecular decompositions. These precursors are divided into two major categories by mechanism of germylene extrusion: {alpha}-elimination precursors and germylacetylenes. The extrusion of germylenes from germylacetylene precursors is of primary interest. A mechanism is proposed employing a germacyclopropene intermediate. Evidence supporting this mechanism is presented. In the process of exploring germylacetylenes as germylene precursors, an apparent dyatropic rearrangement between germanium and silicon was observed. This rearrangement was subsequently explored.

  1. Receptors useful for gas phase chemical sensing

    SciTech Connect

    Jaworski, Justyn W; Lee, Seung-Wuk; Majumdar, Arunava; Raorane, Digvijay A

    2015-02-17

    The invention provides for a receptor, capable of binding to a target molecule, linked to a hygroscopic polymer or hydrogel; and the use of this receptor in a device for detecting the target molecule in a gaseous and/or liquid phase. The invention also provides for a method for detecting the presence of a target molecule in the gas phase using the device. In particular, the receptor can be a peptide capable of binding a 2,4,6-trinitrotoluene (TNT) or 2,4,-dinitrotoluene (DNT).

  2. Study of the thymine molecule: equilibrium structure from joint analysis of gas-phase electron diffraction and microwave data and assignment of vibrational spectra using results of ab initio calculations.

    PubMed

    Vogt, Natalja; Khaikin, Leonid S; Grikina, Olga E; Rykov, Anatolii N; Vogt, Jürgen

    2008-08-21

    Thymine is one of the nucleobases which forms the nucleic acid (NA) base pair with adenine in DNA. The study of molecular structure and dynamics of nucleobases can help to understand and explain some processes in biological systems and therefore it is of interest. Because the scattered intensities on the C, N, and O atoms as well as some bond lengths in thymine are close to each other the structural problem cannot been solved by the gas phase electron diffraction (GED) method alone. Therefore the rotational constants from microvawe (MW) studies and differences in the groups of N-C, C=O, N-H, and C-H bond lengths from MP2 (full)/cc-pVQZ calculations were used as supplementary data. The analysis of GED data was based on the C(s) molecular symmetry according to results of the structure optimizations at the MP2 (full) level using 6-311G (d,p), cc-pVTZ, and cc-pVQZ basis sets confirmed by vibrational frequency calculations with 6-311G (d,p) and cc-pVTZ basis sets. Mean-square amplitudes as well as harmonic and anharmonic vibrational corrections to the internuclear distances (r(e)-r(a)) and to the rotational constants (B(e)(k)-B(0)(k), where k = A, B, C) were calculated from the quadratic (MP2 (full)/cc-pVTZ) and cubic (MP2 (full)/6-311G (d,p)) force constants (the latter were used only for anharmonic corrections). The harmonic force field was scaled using published IR and Raman spectra of the parent and N1,N3-dideuterated species, which were for the first time completely assigned in the present work. The main equilibrium structural parameters of the thymine molecule determined from GED data supplemented by MW rotational constants and results of MP2 calculations are the following (bond lengths in Angstroms and bond angles in degrees with 3sigma in parentheses): r(e) (C5=C6) = 1.344 (16), r(e) (C5-C9) = 1.487 (8), r(e) (N1-C6) = 1.372 (3), r(e) (N1-C2) = 1.377 (3), r(e) (C2-N3) = 1.378 (3), r(e) (N3-C4) = 1.395 (3), r(e) (C2=O7) = 1.210 (1), r(e) (C4=O8) = 1.215 (1

  3. Protein structure mining using a structural alphabet.

    PubMed

    Tyagi, M; de Brevern, A G; Srinivasan, N; Offmann, B

    2008-05-01

    We present a comprehensive evaluation of a new structure mining method called PB-ALIGN. It is based on the encoding of protein structure as 1D sequence of a combination of 16 short structural motifs or protein blocks (PBs). PBs are short motifs capable of representing most of the local structural features of a protein backbone. Using derived PB substitution matrix and simple dynamic programming algorithm, PB sequences are aligned the same way amino acid sequences to yield structure alignment. PBs are short motifs capable of representing most of the local structural features of a protein backbone. Alignment of these local features as sequence of symbols enables fast detection of structural similarities between two proteins. Ability of the method to characterize and align regions beyond regular secondary structures, for example, N and C caps of helix and loops connecting regular structures, puts it a step ahead of existing methods, which strongly rely on secondary structure elements. PB-ALIGN achieved efficiency of 85% in extracting true fold from a large database of 7259 SCOP domains and was successful in 82% cases to identify true super-family members. On comparison to 13 existing structure comparison/mining methods, PB-ALIGN emerged as the best on general ability test dataset and was at par with methods like YAKUSA and CE on nontrivial test dataset. Furthermore, the proposed method performed well when compared to flexible structure alignment method like FATCAT and outperforms in processing speed (less than 45 s per database scan). This work also establishes a reliable cut-off value for the demarcation of similar folds. It finally shows that global alignment scores of unrelated structures using PBs follow an extreme value distribution. PB-ALIGN is freely available on web server called Protein Block Expert (PBE) at http://bioinformatics.univ-reunion.fr/PBE/. PMID:18004784

  4. Structure of giant muscle proteins

    PubMed Central

    Meyer, Logan C.; Wright, Nathan T.

    2013-01-01

    Giant muscle proteins (e.g., titin, nebulin, and obscurin) play a seminal role in muscle elasticity, stretch response, and sarcomeric organization. Each giant protein consists of multiple tandem structural domains, usually arranged in a modular fashion spanning 500 kDa to 4 MDa. Although many of the domains are similar in structure, subtle differences create a unique function of each domain. Recent high and low resolution structural and dynamic studies now suggest more nuanced overall protein structures than previously realized. These findings show that atomic structure, interactions between tandem domains, and intrasarcomeric environment all influence the shape, motion, and therefore function of giant proteins. In this article we will review the current understanding of titin, obscurin, and nebulin structure, from the atomic level through the molecular level. PMID:24376425

  5. Effect of additives on gas-phase catalysis with immobilised Thermoanaerobacter species alcohol dehydrogenase (ADH T).

    PubMed

    Trivedi, A H; Spiess, A C; Daussmann, T; Büchs, J

    2006-07-01

    This paper presents a strategy for preparing an efficient immobilised alcohol dehydrogenase preparation for a gas-phase reaction. The effects of additives such as buffers and sucrose on the immobilisation efficiency (residual activity and protein loading) and on the gas-phase reaction efficiency (initial reaction rate and half-life) of Thermoanaerobacter sp. alcohol dehydrogenase were studied. The reduction of acetophenone to 1-phenylethanol under in situ cofactor regeneration using isopropanol as co-substrate was used as a model reaction at fixed reaction conditions (temperature and thermodynamic activities). A strongly enhanced thermostability of the enzyme in the gas-phase reaction was achieved when the enzyme was immobilised with 50 mM phosphate buffer (pH 7) containing sucrose five times the protein amount (on weight/weight basis). This resulted in a remarkable productivity of 200 g L(-1) day(-1) even at non-optimised reaction conditions. The interaction of additives with the enzyme and water affects the immobilisation and gas-phase efficiencies of the enzyme. However, it was not possible to predict the effect of additives on the gas-phase reaction efficiency even after knowing their effect on the immobilisation efficiency.

  6. Structural and relative energy assessments of DFT functionals and the MP2 method to describe the gas phase methylation of nitronates: [R(1)R(2)CNO2](-) + CH3I.

    PubMed

    Mahmood, Ayyaz; Longo, Ricardo L

    2016-06-22

    The performances of 26 combinations of density-functional theory (DFT) functionals or second-order Møller-Plesset (MP2) methods and basis sets were evaluated for the calculation of the activation energy (Δ(‡)E), the energy available (ΔRCE) to the reactant complex, the energy of reaction (ΔrE), and rotational constants of the main structures involved in the methylation reactions of nitronates, [R(1)R(2)CNO2](-) + CH3I, in the gas phase, where R(1) = R(2) = H, R(1) = H and R(2) = CH3, R(1) = R(2) = CH3, and R(1) + R(2) = c-(CH2)2. The separated reactants and products, the reactant and product complexes, and the transition states were considered, leading to 43 data points for the statistical analysis for each method under assessment. Five statistical quantifiers: the mean signed error (MSE), the mean unsigned error (MUE), the percent mean relative error (% MRE), best and worse (BW), and the confidence interval (CI) were used to assess the performance of methods relative to the CCSD(T)/CBS//MP2/aug-cc-pVTZ reference method. The DFT functionals included the widely applied B3LYP and M06-2X global-hybrids and the recently available DSD-PBEP86, DSD-PBEP86-D3BJ and PWPB95 double-hybrids. The basis sets involved an effective core potential (ECP) for describing the inner electrons of iodine such as LANL2DZdp and aug-cc-pVXZ-PP (X = D, T, and Q), and all-electron basis sets for the remaining atoms. The energy available to the reactant complex is described quite well by all methods, however, only the MP2/aug-cc-pVTZ-PP method provided values within 2 kcal mol(-1) (8.4 kJ mol(-1)) from the reference method for Δ(‡)E and ΔrE. Amongst the DFT methods, the global-hybrid M06-2X functional produced the best overall results including BW and CI. Notice that all methods yielded the smallest Δ(‡)E for the C-methylation pathway. The rotational constants of the reactant complexes and the transition state structures were compared, for which the MP2 method and the M06-2X

  7. Thermochemical aspects of proton transfer in the gas phase.

    PubMed

    Gal, J F; Maria, P C; Raczyńska, E D

    2001-07-01

    The beginning of the twentieth century saw the development of new theories of acidity and basicity, which are currently well accepted. The thermochemistry of proton transfer in the absence of solvent attracted much interest during this period, because of the fundamental importance of the process. Nevertheless, before the 1950s, few data were available, either from lattice energy evaluations or from calculations using the emerging molecular orbital theory. Advances in mass spectrometry during the last 40 years allowed studies of numerous systems with better accuracy. Thousands of accurate gas-phase acidities or basicities are now available, for simple atomic and molecular systems and for large biomolecules. The intrinsic effect of structure on the Brønsted basic or acidic properties of molecules and the influence of solvents have been unravelled. In this tutorial, the basics of the thermodynamic principles involved are given, and the mass spectrometric techniques are briefly reviewed. Advances in the design and measurements of gas-phase superacids and superbases are described. Recent studies concerning biomolecules are also evoked.

  8. Gas-phase Dissociation of homo-DNA Oligonucleotides

    NASA Astrophysics Data System (ADS)

    Stucki, Silvan R.; Désiron, Camille; Nyakas, Adrien; Marti, Simon; Leumann, Christian J.; Schürch, Stefan

    2013-12-01

    Synthetic modified oligonucleotides are of interest for diagnostic and therapeutic applications, as their biological stability, pairing selectivity, and binding strength can be considerably increased by the incorporation of unnatural structural elements. Homo-DNA is an oligonucleotide homologue based on dideoxy-hexopyranosyl sugar moieties, which follows the Watson-Crick A-T and G-C base pairing system, but does not hybridize with complementary natural DNA and RNA. Homo-DNA has found application as a bioorthogonal element in templated chemistry applications. The gas-phase dissociation of homo-DNA has been investigated by ESI-MS/MS and MALDI-MS/MS, and mechanistic aspects of its gas-phase dissociation are discussed. Experiments revealed a charge state dependent preference for the loss of nucleobases, which are released either as neutrals or as anions. In contrast to DNA, nucleobase loss from homo-DNA was found to be decoupled from backbone cleavage, thus resulting in stable products. This renders an additional stage of ion activation necessary in order to generate sequence-defining fragment ions. Upon MS3 of the primary base-loss ion, homo-DNA was found to exhibit unspecific backbone dissociation resulting in a balanced distribution of all fragment ion series.

  9. Structure and dynamics of a protein-surfactant assembly studied by ion-mobility mass spectrometry and molecular dynamics simulations.

    PubMed

    Borysik, Antoni J

    2015-09-01

    The structure and dynamics of a protein-surfactant assembly studied by ion-mobility mass spectrometry (IMS) and vacuum molecular dynamics (MD) simulations is reported. Direct evidence is provided for the ability of the surfactant dodecyl-β-D-maltoside (DDM) to prevent charge-induced unfolding of the membrane protein (PagP) in the gas-phase. Restraints obtained by IMS are used to map the surfactant positions onto the protein surface. Surfactants occupying more exposed positions at the apexes of the β-barrel structure are most in-line with the experimental observations. MD simulations provide additional evidence for this assembly organization through surfactant inversion and migration on the protein structure in the absence of solvent. Surfactant migration entails a net shift from apolar membrane spanning regions to more polar regions of the protein structure with the DDM molecule remaining attached to the protein via headgroup interactions. These data provide evidence for the role of protein-DDM headgroup interactions in stabilizing membrane protein structure from gas-phase unfolding.

  10. Gas-phase thermochemistry of chloropyridines

    NASA Astrophysics Data System (ADS)

    Gomes, José R. B.; Amaral, Luísa M. P. F.; Ribeiro da Silva, Manuel A. V.

    2005-04-01

    The gas-phase standard molar enthalpy of formation of the 2,3,5-trichloropyridine compound was derived from the enthalpies of combustion of the crystalline solid measured by rotating-bomb calorimetry and its enthalpy of sublimation obtained by Calvet microcalorimetry at T = 298.15 K. The standard enthalpies of formation for this compound and for the other chlorosubstituted pyridines were determined by DFT calculations. The experimental enthalpy of formation of 2,3,5-trichloropyridine is (65.8 ± 2.3) kJ mol -1, in excellent agreement with the B3LYP/6-311+G(2d,2p)//B3LYP/6-31G(d) value. The affinity of pyridine to some metal cations was also calculated at the same DFT level of theory and compared with experimental data.

  11. Gas phase acidity of substituted benzenes

    NASA Astrophysics Data System (ADS)

    Bouchoux, Guy

    2011-04-01

    Deprotonation thermochemistry of benzene derivatives C 6H 5X (X = H, F, Cl, OH, NH 2, CN, CHO, NO 2, CH 3, C 2H 5, CHCH 2, CCH) has been examined at the G3B3 level of theory. For X = F, Cl, CN, CHO and NO 2, the most favorable deprotonation site is the ortho position of the phenyl ring. This regio-specificity is directly related to the field/inductive effect of the substituent. G3B3 gas phase acidities, Δ acidH° and Δ acidG°, compare within less than 4 kJ mol -1 with experimental data. A noticeable exception is nitrobenzene for which tabulated acidity appear to be underestimated by ca. 120 kJ mol -1.

  12. Gas phase grown silicon germanium nanocrystals

    NASA Astrophysics Data System (ADS)

    Mohan, A.; Tichelaar, F. D.; Kaiser, M.; Verheijen, M. A.; Schropp, R. E. I.; Rath, J. K.

    2016-09-01

    We report on the gas phase synthesis of highly crystalline and homogeneously alloyed Si1-xGex nanocrystals in continuous and pulsed plasmas. Agglomerated nanocrystals have been produced with remarkable control over their composition by altering the precursor GeH4 gas flow in a continuous plasma. We specially highlight that in the pulsed plasma mode, we obtain quantum-sized free standing alloy nanocrystals with a mean size of 7.3 nm. The presence of Si1-xGex alloy particles is confirmed with multiple techniques, i.e. Raman spectroscopy, XRD (Xray diffraction) and HRTEM (high resolution transmission electron microscopy) studies, with each of these methods consistently yielding the same composition. The nanocrystals synthesized here have potential applications in band-gap engineering for multijunction solar cells.

  13. Infrared photodissociation spectroscopy of protonated neurotransmitters in the gas phase

    NASA Astrophysics Data System (ADS)

    MacLeod, N. A.; Simons, J. P.

    2007-03-01

    Protonated neurotransmitters have been produced in the gas phase via a novel photochemical scheme: complexes of the species of interest, 1-phenylethylamine, 2-amino-1-phenylethanol and the diastereo-isomers, ephedrine and pseudoephedrine, with a suitable proton donor, phenol (or indole), are produced in a supersonic expansion and ionized by resonant two photon ionization of the donor. Efficient proton transfer generates the protonated neurotransmitters, complexed to a phenoxy radical. Absorption of infrared radiation, and subsequent evaporation of the phenoxy tag, coupled with time of flight mass spectrometry, provides vibrational spectra of the protonated (and also hydrated) complexes for comparison with the results of quantum chemical computation. Comparison with the conformational structures of the neutral neurotransmitters (established previously) reveals the effect of protonation on their structure. The photochemical proton transfer strategy allows spectra to be recorded from individual laser shots and their quality compares favourably with that obtained using electro-spray or matrix assisted laser desorption ion sources.

  14. Comparing the gas-phase fragmentation reactions of protonated and radical cations of the tripeptides GXR

    NASA Astrophysics Data System (ADS)

    Wee, Sheena; O'Hair, Richard A. J.; McFadyen, W. David

    2004-05-01

    Electrospray ionization (ESI) mass spectrometry of methanolic solutions of mixtures of the copper salt (2,2':6',2''-terpyridine)copper(II) nitrate monohydrate ([Cu(II)(tpy)(NO3)2].H2O) and a tripeptide GXR (where X = 1 of the 20 naturally occurring amino acids) yielded [Cu(II)(tpy)(GXR)][radical sign]2+ ions, which were then subjected to collision induced dissociation (CID). In all but one case (GRR), these [Cu(II)(tpy)(GXR)][radical sign]2+ ions fragment to form odd electron GXR[radical sign]+ radical cations with sufficient abundance to examine their gas-phase fragmentation reactions. The GXR[radical sign]+ radical cations undergo a diverse range of fragmentation reactions which depend on the nature of the side chain of X. Many of these reactions can be rationalized as arising from the intermediacy of isomeric distonic ions in which the charge (i.e. proton) is sequestered by the highly basic arginine side chain and the radical site is located at various positions on the tripeptide including the peptide back bone and side chains. The radical sites in these distonic ions often direct the fragmentation reactions via the expulsion of small radicals (to yield even electron ions) or small neutrals (to form radical cations). Both classes of reaction can yield useful structural information, allowing for example, distinction between leucine and isoleucine residues. The gas-phase fragmentation reactions of the GXR[radical sign]+ radical cations are also compared to their even electron [GXR+H]+ and [GXR+2H]2+ counterparts. The [GXR+H]+ ions give fewer sequence ions and more small molecule losses while the [GXR+2H]2+ ions yield more sequence information, consistent with the [`]mobile proton model' described in previous studies. In general, all three classes of ions give complementary structural information, but the GXR[radical sign]+ radical cations exhibit a more diverse loss of small species (radicals and neutrals). Finally, links between these gas-phase results and key

  15. De Novo Protein Structure Prediction

    NASA Astrophysics Data System (ADS)

    Hung, Ling-Hong; Ngan, Shing-Chung; Samudrala, Ram

    An unparalleled amount of sequence data is being made available from large-scale genome sequencing efforts. The data provide a shortcut to the determination of the function of a gene of interest, as long as there is an existing sequenced gene with similar sequence and of known function. This has spurred structural genomic initiatives with the goal of determining as many protein folds as possible (Brenner and Levitt, 2000; Burley, 2000; Brenner, 2001; Heinemann et al., 2001). The purpose of this is twofold: First, the structure of a gene product can often lead to direct inference of its function. Second, since the function of a protein is dependent on its structure, direct comparison of the structures of gene products can be more sensitive than the comparison of sequences of genes for detecting homology. Presently, structural determination by crystallography and NMR techniques is still slow and expensive in terms of manpower and resources, despite attempts to automate the processes. Computer structure prediction algorithms, while not providing the accuracy of the traditional techniques, are extremely quick and inexpensive and can provide useful low-resolution data for structure comparisons (Bonneau and Baker, 2001). Given the immense number of structures which the structural genomic projects are attempting to solve, there would be a considerable gain even if the computer structure prediction approach were applicable to a subset of proteins.

  16. The cytotoxic effect of volatile organic compounds of the gas phase of cigarette smoke on lung epithelial cells.

    PubMed

    Pouli, Aristea E; Hatzinikolaou, Dimitris G; Piperi, Christina; Stavridou, Anastasia; Psallidopoulos, Miltiades C; Stavrides, John C

    2003-02-01

    Health effects of cigarette smoke (CS) in humans are well known from both clinical and epidemiological studies. However, the mechanism behind CS toxicity and carcinogenicity remains mainly unknown. Recent studies have pointed to the major importance of the gas phase of CS in generating its cytotoxic effects. In the current study, an exposure system capable of introducing the gas phase of mainstream cigarette smoke deprived of its volatile organic constituents (VOCs) was used to study the role of the nonorganic components of the gas phase on the cytotoxicity of smoke to monolayer cultures of mouse lung epithelial cells. Cell viability was measured by Wst-1 and the lactate dehydrogenase (LDH) assays. In cells treated with increasing doses of mainstream cigarette smoke gas phase (one to nine puffs), a dose-dependent increase in cytotoxicity was observed (one puff, 95% viability; nine puffs, 40% viability). Cell viability of cultures exposed to gas phase with only the nonorganic components was found to be equivalent to control, unexposed cultures, indicating that removal of VOCs resulted in almost eliminating the cytotoxic ability of the gas phase of CS. Furthermore, the removal of VOCs seems to reduce the effects of protein tyrosine nitration mediated through the gas phase constituents. The results obtained suggest the important and decisive role of VOCs in inducing cytotoxic effects.

  17. Protein interfacial structure and nanotoxicology

    NASA Astrophysics Data System (ADS)

    White, John W.; Perriman, Adam W.; McGillivray, Duncan J.; Lin, Jhih-Min

    2009-02-01

    Here we briefly recapitulate the use of X-ray and neutron reflectometry at the air-water interface to find protein structures and thermodynamics at interfaces and test a possibility for understanding those interactions between nanoparticles and proteins which lead to nanoparticle toxicology through entry into living cells. Stable monomolecular protein films have been made at the air-water interface and, with a specially designed vessel, the substrate changed from that which the air-water interfacial film was deposited. This procedure allows interactions, both chemical and physical, between introduced species and the monomolecular film to be studied by reflectometry. The method is briefly illustrated here with some new results on protein-protein interaction between β-casein and κ-casein at the air-water interface using X-rays. These two proteins are an essential component of the structure of milk. In the experiments reported, specific and directional interactions appear to cause different interfacial structures if first, a β-casein monolayer is attacked by a κ-casein solution compared to the reverse. The additional contrast associated with neutrons will be an advantage here. We then show the first results of experiments on the interaction of a β-casein monolayer with a nanoparticle titanium oxide sol, foreshadowing the study of the nanoparticle "corona" thought to be important for nanoparticle-cell wall penetration.

  18. Transferring pharmaceuticals into the gas phase

    NASA Astrophysics Data System (ADS)

    Christen, Wolfgang; Krause, Tim; Rademann, Klaus

    2008-11-01

    The dissolution of molecules of biological interest in supercritical carbon dioxide is investigated using pulsed molecular beam mass spectrometry. Due to the mild processing temperatures of most supercritical fluids, their adiabatic expansion into vacuum permits to transfer even thermally very sensitive substances into the gas phase, which is particularly attractive for pharmaceutical and biomedical applications. In addition, supercritical CO2constitutes a chemically inert solvent that is compatible with hydrocarbon-free ultrahigh vacuum conditions. Here, we report on the dissolution and pulsed supersonic jet expansion of caffeine (C8H10N4O2), the provitamin menadione (C11H8O2), and the amino acid derivative l-phenylalanine tert-butyl ester hydrochloride (C6H5CH2CH(NH2)COOC(CH3)3[dot operator]HCl), into vacuum. An on-axis residual gas analyzer is used to monitor the relative amounts of solute and solvent in the molecular beam as a function of solvent densityE The excellent selectivity and sensitivity provided by mass spectrometry permits to probe even trace amounts of solutes. The strong density variation of CO2 close to the critical point results in a pronounced pressure dependence of the relative ion currents of solute and solvent molecules, reflecting a substantial change in solubility.

  19. Method for protein structure alignment

    DOEpatents

    Blankenbecler, Richard; Ohlsson, Mattias; Peterson, Carsten; Ringner, Markus

    2005-02-22

    This invention provides a method for protein structure alignment. More particularly, the present invention provides a method for identification, classification and prediction of protein structures. The present invention involves two key ingredients. First, an energy or cost function formulation of the problem simultaneously in terms of binary (Potts) assignment variables and real-valued atomic coordinates. Second, a minimization of the energy or cost function by an iterative method, where in each iteration (1) a mean field method is employed for the assignment variables and (2) exact rotation and/or translation of atomic coordinates is performed, weighted with the corresponding assignment variables.

  20. Tuning a High Transmission Ion Guide to Prevent Gas-Phase Proton Exchange During H/D Exchange MS Analysis

    NASA Astrophysics Data System (ADS)

    Guttman, Miklos; Wales, Thomas E.; Whittington, Dale; Engen, John R.; Brown, Jeffery M.; Lee, Kelly K.

    2016-04-01

    Hydrogen/deuterium exchange (HDX) mass spectrometry (MS) for protein structural analysis has been adopted for many purposes, including biopharmaceutical development. One of the benefits of examining amide proton exchange by mass spectrometry is that it can readily resolve different exchange regimes, as evidenced by either binomial or bimodal isotope patterns. By careful analysis of the isotope pattern during exchange, more insight can be obtained on protein behavior in solution. However, one must be sure that any observed bimodal isotope patterns are not artifacts of analysis and are reflective of the true behavior in solution. Sample carryover and certain stationary phases are known as potential sources of bimodal artifacts. Here, we describe an additional undocumented source of deuterium loss resulting in artificial bimodal patterns for certain highly charged peptides. We demonstrate that this phenomenon is predominantly due to gas-phase proton exchange between peptides and bulk solvent within the initial stages of high-transmission conjoined ion guides. Minor adjustments of the ion guide settings, as reported here, eliminate the phenomenon without sacrificing signal intensity. Such gas-phase deuterium loss should be appreciated for all HDX-MS studies using such ion optics, even for routine studies not focused on interpreting bimodal spectra.

  1. A Protocol for Detecting and Scavenging Gas-phase Free Radicals in Mainstream Cigarette Smoke

    PubMed Central

    Yu, Long-Xi; Dzikovski, Boris G.; Freed, Jack H.

    2012-01-01

    Cigarette smoking is associated with human cancers. It has been reported that most of the lung cancer deaths are caused by cigarette smoking 5,6,7,12. Although tobacco tars and related products in the particle phase of cigarette smoke are major causes of carcinogenic and mutagenic related diseases, cigarette smoke contains significant amounts of free radicals that are also considered as an important group of carcinogens9,10. Free radicals attack cell constituents by damaging protein structure, lipids and DNA sequences and increase the risks of developing various types of cancers. Inhaled radicals produce adducts that contribute to many of the negative health effects of tobacco smoke in the lung3. Studies have been conducted to reduce free radicals in cigarette smoke to decrease risks of the smoking-induced damage. It has been reported that haemoglobin and heme-containing compounds could partially scavenge nitric oxide, reactive oxidants and carcinogenic volatile nitrosocompounds of cigarette smoke4. A 'bio-filter' consisted of haemoglobin and activated carbon was used to scavenge the free radicals and to remove up to 90% of the free radicals from cigarette smoke14. However, due to the cost-ineffectiveness, it has not been successfully commercialized. Another study showed good scavenging efficiency of shikonin, a component of Chinese herbal medicine8. In the present study, we report a protocol for introducing common natural antioxidant extracts into the cigarette filter for scavenging gas phase free radicals in cigarette smoke and measurement of the scavenge effect on gas phase free radicals in mainstream cigarette smoke (MCS) using spin-trapping Electron Spin Resonance (ESR) Spectroscopy1,2,14. We showed high scavenging capacity of lycopene and grape seed extract which could point to their future application in cigarette filters. An important advantage of these prospective scavengers is that they can be obtained in large quantities from byproducts of tomato or wine

  2. A protocol for detecting and scavenging gas-phase free radicals in mainstream cigarette smoke.

    PubMed

    Yu, Long-Xi; Dzikovski, Boris G; Freed, Jack H

    2012-01-02

    Cigarette smoking is associated with human cancers. It has been reported that most of the lung cancer deaths are caused by cigarette smoking (5,6,7,12). Although tobacco tars and related products in the particle phase of cigarette smoke are major causes of carcinogenic and mutagenic related diseases, cigarette smoke contains significant amounts of free radicals that are also considered as an important group of carcinogens(9,10). Free radicals attack cell constituents by damaging protein structure, lipids and DNA sequences and increase the risks of developing various types of cancers. Inhaled radicals produce adducts that contribute to many of the negative health effects of tobacco smoke in the lung(3). Studies have been conducted to reduce free radicals in cigarette smoke to decrease risks of the smoking-induced damage. It has been reported that haemoglobin and heme-containing compounds could partially scavenge nitric oxide, reactive oxidants and carcinogenic volatile nitrosocompounds of cigarette smoke(4). A 'bio-filter' consisted of haemoglobin and activated carbon was used to scavenge the free radicals and to remove up to 90% of the free radicals from cigarette smoke(14). However, due to the cost-ineffectiveness, it has not been successfully commercialized. Another study showed good scavenging efficiency of shikonin, a component of Chinese herbal medicine(8). In the present study, we report a protocol for introducing common natural antioxidant extracts into the cigarette filter for scavenging gas phase free radicals in cigarette smoke and measurement of the scavenge effect on gas phase free radicals in mainstream cigarette smoke (MCS) using spin-trapping Electron Spin Resonance (ESR) Spectroscopy(1,2,14). We showed high scavenging capacity of lycopene and grape seed extract which could point to their future application in cigarette filters. An important advantage of these prospective scavengers is that they can be obtained in large quantities from byproducts of

  3. Infrared spectra of gas-phase polycyclic aromatic hydrocarbon molecules

    SciTech Connect

    Zhang, Keqing; Guo, B.; Bernath, P.F.

    1995-12-31

    Recording the spectra of gas-phase polycyclic aromatic hydrocarbon molecules is of great astronomical interest. Infrared spectra of gas-phase naphthalene, pyrene, and chrysene were obtained in absorption and emission. The band positions and relative intensities were measured and compared with theoretical calculations. These data will be compared to the astronomical observations of the unidentified infrared emission bands.

  4. Pressure Dependence of Gas-Phase Reaction Rates

    ERIC Educational Resources Information Center

    De Persis, Stephanie; Dollet, Alain; Teyssandier, Francis

    2004-01-01

    It is presented that only simple concepts, mainly taken from activated-complex or transition-state theory, are required to explain and analytically describe the influence of pressure on gas-phase reaction kinetics. The simplest kind of elementary gas-phase reaction is a unimolecular decomposition reaction.

  5. Hydrocarbon radical thermochemistry: Gas-phase ion chemistry techniques

    SciTech Connect

    Ervin, Kent M.

    2014-03-21

    Final Scientific/Technical Report for the project "Hydrocarbon Radical Thermochemistry: Gas-Phase Ion Chemistry Techniques." The objective of this project is to exploit gas-phase ion chemistry techniques for determination of thermochemical values for neutral hydrocarbon radicals of importance in combustion kinetics.

  6. Polymerization in the gas phase, in clusters, and on nanoparticle surfaces.

    PubMed

    El-Shall, M Samy

    2008-07-01

    Gas phase and cluster experiments provide unique opportunities to quantitatively study the effects of initiators, solvents, chain transfer agents, and inhibitors on the mechanisms of polymerization. Furthermore, a number of important phenomena, unique structures, and novel properties may exist during gas-phase and cluster polymerization. In this regime, the structure of the growing polymer may change dramatically and the rate coefficient may vary significantly upon the addition of a single molecule of the monomer. These changes would be reflected in the properties of the oligomers deposited from the gas phase. At low pressures, cationic and radical cationic polymerizations may proceed in the gas phase through elimination reactions. In the same systems at high pressure, however, the ionic intermediates may be stabilized, and addition without elimination may occur. In isolated van der Waals clusters of monomer molecules, sequential polymerization with several condensation steps can occur on a time scale of a few microseconds following the ionization of the gas-phase cluster. The cluster reactions, which bridge gas-phase and condensed-phase chemistry, allow examination of the effects of controlled states of aggregation. This Account describes several examples of gas-phase and cluster polymerization studies where the most significant results can be summarized as follows: (1) The carbocation polymerization of isobutene shows slower rates with increasing polymerization steps resulting from entropy barriers, which could explain the need for low temperatures for the efficient propagation of high molecular weight polymers. (2) Radical cation polymerization of propene can be initiated by partial charge transfer from an ionized aromatic molecule such as benzene coupled with covalent condensation of the associated propene molecules. This novel mechanism leads exclusively to the formation of propene oligomer ions and avoids other competitive products. (3) Structural information

  7. Polymerization in the gas phase, in clusters, and on nanoparticle surfaces.

    PubMed

    El-Shall, M Samy

    2008-07-01

    Gas phase and cluster experiments provide unique opportunities to quantitatively study the effects of initiators, solvents, chain transfer agents, and inhibitors on the mechanisms of polymerization. Furthermore, a number of important phenomena, unique structures, and novel properties may exist during gas-phase and cluster polymerization. In this regime, the structure of the growing polymer may change dramatically and the rate coefficient may vary significantly upon the addition of a single molecule of the monomer. These changes would be reflected in the properties of the oligomers deposited from the gas phase. At low pressures, cationic and radical cationic polymerizations may proceed in the gas phase through elimination reactions. In the same systems at high pressure, however, the ionic intermediates may be stabilized, and addition without elimination may occur. In isolated van der Waals clusters of monomer molecules, sequential polymerization with several condensation steps can occur on a time scale of a few microseconds following the ionization of the gas-phase cluster. The cluster reactions, which bridge gas-phase and condensed-phase chemistry, allow examination of the effects of controlled states of aggregation. This Account describes several examples of gas-phase and cluster polymerization studies where the most significant results can be summarized as follows: (1) The carbocation polymerization of isobutene shows slower rates with increasing polymerization steps resulting from entropy barriers, which could explain the need for low temperatures for the efficient propagation of high molecular weight polymers. (2) Radical cation polymerization of propene can be initiated by partial charge transfer from an ionized aromatic molecule such as benzene coupled with covalent condensation of the associated propene molecules. This novel mechanism leads exclusively to the formation of propene oligomer ions and avoids other competitive products. (3) Structural information

  8. Gas-Phase Dissociation Pathways of Multiply Charged Peptide Clusters

    PubMed Central

    Jurchen, John C.; Garcia, David E.; Williams, Evan R.

    2005-01-01

    Numerous studies of cluster formation and dissociation have been conducted to determine properties of matter in the transition from the condensed phase to the gas phase using materials as diverse as atomic nuclei, noble gasses, metal clusters, and amino acids. Here, electrospray ionization is used to extend the study of cluster dissociation to peptides including leucine enkephalin with 7–19 monomer units and 2–5 protons, and somatostatin with 5 monomer units and 4 protons under conditions where its intramolecular disulfide bond is either oxidized or reduced. Evaporation of neutral monomers and charge separation by cluster fission are the competing dissociation pathways of both peptides. The dominant fission product for all leucine enkephalin clusters studied is a proton-bound dimer, presumably due to the high gas-phase stability of this species. The branching ratio of the fission and evaporation processes for leucine enkephalin clusters appears to be determined by the value of z2/n for the cluster where z is the charge and n the number of monomer units in the cluster. Clusters with low and high values of z2/n dissociate primarily by evaporation and cluster fission respectively, with a sharp transition between dissociation primarily by evaporation and primarily by fission measured at a z2/n value of ~0.5. The dependence of the dissociation pathway of a cluster on z2/n is similar to the dissociation of atomic nuclei and multiply charged metal clusters indicating that leucine enkephalin peptide clusters exist in a state that is more disordered, and possibly fluid, rather than highly structured in the dissociative transition state. The branching ratio, but not the dissociation pathway of [somatostatin5 + 4H]4+ is altered by the reduction of its internal disulfide bond indicating that monomer conformational flexibility plays a role in peptide cluster dissociation. PMID:14652186

  9. Gas-phase synthesis and reactivity of Cu(+)-benzyne complexes.

    PubMed

    Chai, Yunfeng; Shen, Shanshan; Weng, Guofeng; Pan, Yuanjiang

    2014-10-11

    Cu(+)-benzyne complexes bearing bidentate nitrogen ligands were synthesized in the gas phase for the first time using electrospray ionization mass spectrometry. The addition reactivity of copper-stabilized benzyne with amines was studied in the ion trap analyzer. The structures of products were identified by comparing their MS(n) data with authentic compounds obtained from another generation route.

  10. Field ionization kinetic and electron impact studies of gas phase transition states - The cyclic bromonium ion

    NASA Technical Reports Server (NTRS)

    Green, M. M.; Giguere, R. J.; Falick, A. M.; Aberth, W.; Burlingame, A. L.

    1978-01-01

    Cis- and trans-isomers of 4-t-butylcyclohexyl bromide were studied to determine the mechanism of cyclic bromonium ion formation. The field ionization kinetic and electron impact data indicate that the formation of the cyclic structure occurs simultaneously with loss of the neutral fragment. The data also show that little or no gas-phase cis-trans isomerization occurs.

  11. Protein Structure Comparison and Classification

    NASA Astrophysics Data System (ADS)

    Çamoǧlu, Orhan; Singh, Ambuj K.

    The success of genome projects has generated an enormous amount of sequence data. In order to realize the full value of the data, we need to understand its functional role and its evolutionary origin. Sequence comparison methods are incredibly valuable for this task. However, for sequences falling in the twilight zone (usually between 20 and 35% sequence similarity), we need to resort to structural alignment and comparison for a meaningful analysis. Such a structural approach can be used for classification of proteins, isolation of structural motifs, and discovery of drug targets.

  12. Sucralose Destabilization of Protein Structure.

    PubMed

    Chen, Lee; Shukla, Nimesh; Cho, Inha; Cohn, Erin; Taylor, Erika A; Othon, Christina M

    2015-04-16

    Sucralose is a commonly employed artificial sweetener that behaves very differently than its natural disaccharide counterpart, sucrose, in terms of its interaction with biomolecules. The presence of sucralose in solution is found to destabilize the native structure of two model protein systems: the globular protein bovine serum albumin and an enzyme staphylococcal nuclease. The melting temperature of these proteins decreases as a linear function of sucralose concentration. We correlate this destabilization to the increased polarity of the molecule. The strongly polar nature is manifested as a large dielectric friction exerted on the excited-state rotational diffusion of tryptophan using time-resolved fluorescence anisotropy. Tryptophan exhibits rotational diffusion proportional to the measured bulk viscosity for sucrose solutions over a wide range of concentrations, consistent with a Stokes-Einstein model. For sucralose solutions, however, the diffusion is dependent on the concentration, strongly diverging from the viscosity predictions, and results in heterogeneous rotational diffusion. PMID:26263149

  13. Vibrational Spectroscopy and Gas-Phase Thermochemistry of the Model Dipeptide N-Acetyl Glycine Methyl Amide

    NASA Astrophysics Data System (ADS)

    Leavitt, Christopher; Raston, Paul; Moody, Grant; Shirley, Caitlyne; Douberly, Gary

    2014-06-01

    The structure-function relationship in proteins is widely recognized, motivating numerous investigations of isolated neutral and ionic polypeptides that generally employ conformation specific, multidimensional UV and IR spectroscopies. This data taken in conjunction with computed harmonic frequencies has provided a snapshot of the underlying molecular physics at play in many polypeptides, but few experiments have been able to probe the energetics of these systems. In this study, we use vibrational spectroscopy to measure the gas-phase enthalpy change for isomerization between two conformations of the dipeptide N-acetyl glycine methyl amide (NAGMA). A two-stage oven source is implemented producing a gas-phase equilibrium distribution of NAGMA molecules that is flash frozen upon pickup by He nanodroplets. Using polarization spectroscopy, the IR spectrum is assigned to a mixture of two conformers having intramolecular hydrogen bonds made up of either five- or seven-membered rings, C5 and C7, respectively. The interconversion enthalpy, obtained from the van't Hoff relation, is 4.52{±}0.12 kJ/mol for isomerization from the C7 to the C5-conformer. This experimental measurement is compared to computations employing a broad range of theoretical methods.

  14. Methods of protein structure comparison

    PubMed Central

    Kufareva, Irina; Abagyan, Ruben

    2015-01-01

    Despite its apparent simplicity, the problem of quantifying the differences between two structures of the same protein or complex is non-trivial and continues evolving. In this chapter, we described several methods routinely used to compare computational models to experimental answers in several modeling assessments. The two major classes of measures, positional distance-based and contact-based, were presented, compared and analyzed. The most popular measure of the first class, the global RMSD, is shown to be the least representative of the degree of structural similarity because it is dominated by the largest error. Several distance-dependent algorithms designed to attenuate the drawbacks of RMSD are described. Measures of the second class, contact-based, are shown to be more robust and relevant. We also illustrate the importance of using combined measures, utility-based measures, and the role of the distributions derived from the pairs of experimental structures in interpreting the results. PMID:22323224

  15. An empirical model for gas phase acidity and basicity estimation.

    PubMed

    You, H; Kim, G E; Na, C H; Lee, S; Lee, C J; Cho, K-H; Akiyama, Y; Ishida, T; No, K T

    2014-01-01

    Gas phase acidity and basicity estimation models have been developed for acidic and basic functional groups of amino acid side-chains and also for a number of small organic molecules. The acidic functional groups include aliphatic and aromatic alcohol, and aliphatic and aromatic carboxylic acid, and the basic functional groups include aliphatic, aromatic and hetero-aromatic amines, and also pyridino-, pyrazolo- and imidazolo-groupings. The models are described in terms of a linear combination of descriptors that highly influence reactivity at the reaction centres of the functional groups. In order to describe the chemical environments of the deprotonating and protonating sites, atomic descriptors such as the effective atomic electronegativity and effective atomic polarizability of the atoms in the reaction field and the electrostatic potentials at the reaction sites have been introduced. The coefficient of determination (r(2)) of each model is above 0.8, apart from the imidazole model. The models are readily applicable, ranging from simple organic molecules to proteins.

  16. The molecular structure of silyl cyanide, determined in the gas phase by electron diffraction, microwave spectroscopy and high resolution infra-red spectroscopy, in solution in a nematic phase by NMR spectroscopy, and in the crystalline phase at 100 K by X-ray crystallography

    NASA Astrophysics Data System (ADS)

    Blair, Peter D.; Blake, Alexander J.; Cockman, Russell W.; Cradock, Stephen; Ebsworth, E. A. V.; Rankin, David W. H.

    1989-02-01

    The molecular structure of silyl cyanide has been determined in the gas phase by analysis of electron diffraction data and rotation constants, both separately and together, in solution in a nematic liquid crystal by NMR spectroscopy, and in the crystalline phase at 100 K by X-ray crystallography. In the gas phase the parameters ( rav) are: SiC 184.96(4), CN 115.63(5), SiH 148.73(11) pm and ∠HSiC 107.25(4)°. In the crystalline phase the molecules lie on mirror planes, with near-linear chains of molecules ⋯SiCN⋯SiCN⋯. The non-bonded N⋯Si distance is 278.9(2) pm, and this fairly strong interaction is associated with lengthening of the SiC bondlength to 189.96(18) pm, and narrowing of the HSiC angles to 100.4(7)°. The CN distance is 114.28(23) pm. Angles in the chain are SiCN 179.04(15), N⋯SiC 177.62(6) and CN⋯Si 176.66(13)°. In solution in a liquid crystal solvent the structure ( rα°) also shows narrowing of the HSiC angles, to 104.84(14)°. Absolute values of bondlengths cannot be determined by this method, but the ratios r(SiH): r(CN) = 1.2762(24) and r(SiC): r(CN) = 1.6374(34) are consistent with a structure midway between those observed in the gaseous and crystalline phases. Interaction between cyanide groups in the solvent and silyl groups is postulated to account for this behaviour.

  17. Introduction to Protein Structure through Genetic Diseases

    ERIC Educational Resources Information Center

    Schneider, Tanya L.; Linton, Brian R.

    2008-01-01

    An illuminating way to learn about protein function is to explore high-resolution protein structures. Analysis of the proteins involved in genetic diseases has been used to introduce students to protein structure and the role that individual mutations can play in the onset of disease. Known mutations can be correlated to changes in protein…

  18. Protein structure alignment beyond spatial proximity.

    PubMed

    Wang, Sheng; Ma, Jianzhu; Peng, Jian; Xu, Jinbo

    2013-01-01

    Protein structure alignment is a fundamental problem in computational structure biology. Many programs have been developed for automatic protein structure alignment, but most of them align two protein structures purely based upon geometric similarity without considering evolutionary and functional relationship. As such, these programs may generate structure alignments which are not very biologically meaningful from the evolutionary perspective. This paper presents a novel method DeepAlign for automatic pairwise protein structure alignment. DeepAlign aligns two protein structures using not only spatial proximity of equivalent residues (after rigid-body superposition), but also evolutionary relationship and hydrogen-bonding similarity. Experimental results show that DeepAlign can generate structure alignments much more consistent with manually-curated alignments than other automatic tools especially when proteins under consideration are remote homologs. These results imply that in addition to geometric similarity, evolutionary information and hydrogen-bonding similarity are essential to aligning two protein structures.

  19. An Interactive Introduction to Protein Structure

    ERIC Educational Resources Information Center

    Lee, W. Theodore

    2004-01-01

    To improve student understanding of protein structure and the significance of noncovalent interactions in protein structure and function, students are assigned a project to write a paper complemented with computer-generated images. The assignment provides an opportunity for students to select a protein structure that is of interest and detail…

  20. SDSL-ESR-based protein structure characterization.

    PubMed

    Strancar, Janez; Kavalenka, Aleh; Urbancic, Iztok; Ljubetic, Ajasja; Hemminga, Marcus A

    2010-03-01

    As proteins are key molecules in living cells, knowledge about their structure can provide important insights and applications in science, biotechnology, and medicine. However, many protein structures are still a big challenge for existing high-resolution structure-determination methods, as can be seen in the number of protein structures published in the Protein Data Bank. This is especially the case for less-ordered, more hydrophobic and more flexible protein systems. The lack of efficient methods for structure determination calls for urgent development of a new class of biophysical techniques. This work attempts to address this problem with a novel combination of site-directed spin labelling electron spin resonance spectroscopy (SDSL-ESR) and protein structure modelling, which is coupled by restriction of the conformational spaces of the amino acid side chains. Comparison of the application to four different protein systems enables us to generalize the new method and to establish a general procedure for determination of protein structure.

  1. Multidimensional separations of ubiquitin conformers in the gas phase: relating ion cross sections to H/D exchange measurements.

    PubMed

    Robinson, Errol W; Williams, Evan R

    2005-09-01

    Investigating gas-phase structures of protein ions can lead to an improved understanding of intramolecular forces that play an important role in protein folding. Both hydrogen/deuterium (H/D) exchange and ion mobility spectrometry provide insight into the structures and stabilities of different gas-phase conformers, but how best to relate the results from these two methods has been hotly debated. Here, high-field asymmetric waveform ion mobility spectrometry (FAIMS) is combined with Fourier-transform ion cyclotron resonance mass spectrometry (FT/ICR MS) and is used to directly relate ubiquitin ion cross sections and H/D exchange extents. Multiple conformers can be identified using both methods. For the 9+ charge state of ubiquitin, two conformers (or unresolved populations of conformers) that have cross sections differing by 10% are resolved by FAIMS, but only one conformer is apparent using H/D exchange at short times. For the 12+ charge state, two conformers (or conformer populations) have cross sections differing by <1%, yet H/D exchange of these conformers differ significantly (6 versus 25 exchanges). These and other results show that ubiquitin ion collisional cross sections and H/D exchange distributions are not strongly correlated and that factors other than surface accessibility appear to play a significant role in determining rates and extents of H/D exchange. Conformers that are not resolved by one method could be resolved by the other, indicating that these two methods are highly complementary and that more conformations can be resolved with this combination of methods than by either method alone.

  2. Gas-phase chemistry of alkylcarbonate anions and radicals

    NASA Astrophysics Data System (ADS)

    Soldi-Lose, Héloïse; Schröder, Detlef; Schwarz, Helmut

    2008-02-01

    Alkylcarbonate anions and radicals ROCOO-/ (R = H, CH3, C2H5, i-C3H7, and t-C4H9) are investigated in the gas phase by means of mass spectrometry and ab initio calculations. Structural parameters and energies are obtained at the MP2/6-311++G(3df,3pd)//MP2/6-311++G(d,p) level of theoryE Standard enthalpies of formation for the anions and radicals are determined via atomization energies and isodesmic reactions using the CBS-Q method. Further, alkylcarbonate anions are probed by metastable ion and collisional activation experiments, and the chemistry of the neutral radicals is investigated by charge-reversal and neutralization-reionization mass spectrometry. Although decarboxylation dominates the unimolecular reactivity of the species for both charge states, some other interesting features are observed, particularly for the anions, such as the formation of the CO3- radical anion or the presence of ionic fragments formed via hydrogen atom transfer.

  3. Gas-phase electronic spectrum of the indole radical cation

    NASA Astrophysics Data System (ADS)

    Chalyavi, N.; Catani, K. J.; Sanelli, J. A.; Dryza, V.; Bieske, E. J.

    2015-08-01

    The visible and near-UV electronic spectrum of the indole radical cation is measured in the gas phase by photodissociation of indole+-Ar and indole+-He complexes in a tandem mass spectrometer. A series of resolved vibronic transitions extending from 610 to 460 nm are assigned to the D2 ← D0 band system, while weak transitions between 390 and 360 nm are assigned to the D3 ← D0 system, and a stronger, broad, unresolved absorption between 350 and 300 nm is attributed to the D4 ← D0 system. Time-dependent density functional theory calculations are used to assign vibronic structure of the D2 ← D0 band system, and show that the main active vibrational modes correspond to in-plane ring deformations. The strongest D2 ← D0 vibronic transitions of indole+-He do not correspond with any catalogued diffuse interstellar bands, even considering band displacements of up to 50 cm-1possibly caused by the attached He atom.

  4. Structure Prediction of Protein Complexes

    NASA Astrophysics Data System (ADS)

    Pierce, Brian; Weng, Zhiping

    Protein-protein interactions are critical for biological function. They directly and indirectly influence the biological systems of which they are a part. Antibodies bind with antigens to detect and stop viruses and other infectious agents. Cell signaling is performed in many cases through the interactions between proteins. Many diseases involve protein-protein interactions on some level, including cancer and prion diseases.

  5. Modularity in protein structures: study on all-alpha proteins.

    PubMed

    Khan, Taushif; Ghosh, Indira

    2015-01-01

    Modularity is known as one of the most important features of protein's robust and efficient design. The architecture and topology of proteins play a vital role by providing necessary robust scaffolds to support organism's growth and survival in constant evolutionary pressure. These complex biomolecules can be represented by several layers of modular architecture, but it is pivotal to understand and explore the smallest biologically relevant structural component. In the present study, we have developed a component-based method, using protein's secondary structures and their arrangements (i.e. patterns) in order to investigate its structural space. Our result on all-alpha protein shows that the known structural space is highly populated with limited set of structural patterns. We have also noticed that these frequently observed structural patterns are present as modules or "building blocks" in large proteins (i.e. higher secondary structure content). From structural descriptor analysis, observed patterns are found to be within similar deviation; however, frequent patterns are found to be distinctly occurring in diverse functions e.g. in enzymatic classes and reactions. In this study, we are introducing a simple approach to explore protein structural space using combinatorial- and graph-based geometry methods, which can be used to describe modularity in protein structures. Moreover, analysis indicates that protein function seems to be the driving force that shapes the known structure space.

  6. Protein enriched pasta: structure and digestibility of its protein network.

    PubMed

    Laleg, Karima; Barron, Cécile; Santé-Lhoutellier, Véronique; Walrand, Stéphane; Micard, Valérie

    2016-02-01

    Wheat (W) pasta was enriched in 6% gluten (G), 35% faba (F) or 5% egg (E) to increase its protein content (13% to 17%). The impact of the enrichment on the multiscale structure of the pasta and on in vitro protein digestibility was studied. Increasing the protein content (W- vs. G-pasta) strengthened pasta structure at molecular and macroscopic scales but reduced its protein digestibility by 3% by forming a higher covalently linked protein network. Greater changes in the macroscopic and molecular structure of the pasta were obtained by varying the nature of protein used for enrichment. Proteins in G- and E-pasta were highly covalently linked (28-32%) resulting in a strong pasta structure. Conversely, F-protein (98% SDS-soluble) altered the pasta structure by diluting gluten and formed a weak protein network (18% covalent link). As a result, protein digestibility in F-pasta was significantly higher (46%) than in E- (44%) and G-pasta (39%). The effect of low (55 °C, LT) vs. very high temperature (90 °C, VHT) drying on the protein network structure and digestibility was shown to cause greater molecular changes than pasta formulation. Whatever the pasta, a general strengthening of its structure, a 33% to 47% increase in covalently linked proteins and a higher β-sheet structure were observed. However, these structural differences were evened out after the pasta was cooked, resulting in identical protein digestibility in LT and VHT pasta. Even after VHT drying, F-pasta had the best amino acid profile with the highest protein digestibility, proof of its nutritional interest.

  7. Protein enriched pasta: structure and digestibility of its protein network.

    PubMed

    Laleg, Karima; Barron, Cécile; Santé-Lhoutellier, Véronique; Walrand, Stéphane; Micard, Valérie

    2016-02-01

    Wheat (W) pasta was enriched in 6% gluten (G), 35% faba (F) or 5% egg (E) to increase its protein content (13% to 17%). The impact of the enrichment on the multiscale structure of the pasta and on in vitro protein digestibility was studied. Increasing the protein content (W- vs. G-pasta) strengthened pasta structure at molecular and macroscopic scales but reduced its protein digestibility by 3% by forming a higher covalently linked protein network. Greater changes in the macroscopic and molecular structure of the pasta were obtained by varying the nature of protein used for enrichment. Proteins in G- and E-pasta were highly covalently linked (28-32%) resulting in a strong pasta structure. Conversely, F-protein (98% SDS-soluble) altered the pasta structure by diluting gluten and formed a weak protein network (18% covalent link). As a result, protein digestibility in F-pasta was significantly higher (46%) than in E- (44%) and G-pasta (39%). The effect of low (55 °C, LT) vs. very high temperature (90 °C, VHT) drying on the protein network structure and digestibility was shown to cause greater molecular changes than pasta formulation. Whatever the pasta, a general strengthening of its structure, a 33% to 47% increase in covalently linked proteins and a higher β-sheet structure were observed. However, these structural differences were evened out after the pasta was cooked, resulting in identical protein digestibility in LT and VHT pasta. Even after VHT drying, F-pasta had the best amino acid profile with the highest protein digestibility, proof of its nutritional interest. PMID:26829164

  8. Counting basic sites in oligopeptides via gas-phase ion chemistry

    SciTech Connect

    Stephenson, J.L. Jr.; McLuckey, S.A.

    1997-02-01

    Cations derived from oligopeptides ranging from laminin fragment (5 residues) to {beta}-lactoglobulin (162 residues) have been subjected to gas-phase ion/molecule reactions with hydroiodic acid. The sum of the ion charge state and the maximum number of molecules of hydroiodic acid that attach to the ion is equal to the total number of lysines, arginines, histidines, and N-termini consisting of a primary amine for ions derived from all 21 oligopeptides studied. These results suggest that ion/molecule reactions can provide useful information regarding oligopeptide basic site number, which might be used as a criterion for searching protein data bases instead of, or in conjunction with, use of proteolytic digestion or gas-phase ion dissociation procedures. 31 refs., 3 figs., 1 tab.

  9. Sucralose Destabilization of Protein Structure

    NASA Astrophysics Data System (ADS)

    Cho, Inha; Chen, Lee; Shukla, Nimesh; Othon, Christina

    2015-03-01

    Sucralose is a commonly employed artificial sweetener. Sucralose behaves very differently than its natural disaccharide counterpart, sucrose, in terms of its interaction with biomolecules. The presence of sucralose in solution is found to destabilize the native structure of the globular protein Bovine Serum Albumin (BSA). The melting temperature decreases as a linear function of sucralose concentration. We correlate this destabilization with the increased polarity of the sucralose molecule as compared to sucrose. The strongly polar nature is observed as a large dielectric friction exerted on the excited state rotational diffusion of tryptophan using time-resolved fluorescence anisotropy. Tryptophan exhibits rotational diffusion proportional to the measured bulk viscosity for sucrose solutions over a wide range of concentrations, consistent with a Stokes-Einstein diffusional model. For sucralose solutions however, the diffusion is linearly dependent with the concentration, strongly diverging from the viscosity predictions. The polar nature of sucralose causes a dramatically different interaction with biomolecules than natural disaccharide molecules. Connecticut Space Grant Consortium.

  10. [Protein structure: Folding and prions].

    PubMed

    Rey-Gayo, Antonio; Calbo Torrecilla, Francisco

    2002-04-01

    Transmissible spongiform encephalopathies have become a subject of prime social concern in recent years because of its relation to "mad cow disease" and their potential for transmission to humans. Among the most important scientific aspects of these diseases are the peculiar characteristics of the agent involved in their transmission. In this article we briefly describe the outstanding features of prions, the most widely accepted hypothesis for these diseases. We focus on the molecular characteristics of this protein, coded in the genome of the affected host, and describe the conformational alterations in the protein's tertiary structure that have been blamed for its pathologic activity. Our aim is to summarize the state-of-the-art knowledge on prions, the hypotheses proposed to explain mechanisms of disease transmission without agents containing genetic material, and some specific peculiarities of this new infectious agent. The links between this knowledge and possible therapeutic strategies to overcome the disease justify, once again, close interaction among chemistry, molecular biology, and medicine. PMID:11996702

  11. PDBFlex: exploring flexibility in protein structures

    PubMed Central

    Hrabe, Thomas; Li, Zhanwen; Sedova, Mayya; Rotkiewicz, Piotr; Jaroszewski, Lukasz; Godzik, Adam

    2016-01-01

    The PDBFlex database, available freely and with no login requirements at http://pdbflex.org, provides information on flexibility of protein structures as revealed by the analysis of variations between depositions of different structural models of the same protein in the Protein Data Bank (PDB). PDBFlex collects information on all instances of such depositions, identifying them by a 95% sequence identity threshold, performs analysis of their structural differences and clusters them according to their structural similarities for easy analysis. The PDBFlex contains tools and viewers enabling in-depth examination of structural variability including: 2D-scaling visualization of RMSD distances between structures of the same protein, graphs of average local RMSD in the aligned structures of protein chains, graphical presentation of differences in secondary structure and observed structural disorder (unresolved residues), difference distance maps between all sets of coordinates and 3D views of individual structures and simulated transitions between different conformations, the latter displayed using JSMol visualization software. PMID:26615193

  12. Oscillatory burning of solid propellants including gas phase time lag.

    NASA Technical Reports Server (NTRS)

    T'Ien, J. S.

    1972-01-01

    An analysis has been performed for oscillatory burning of solid propellants including gas phase time lag. The gaseous flame is assumed to be premixed and laminar with a one-step overall chemical reaction. The propellant is assumed to decompose according to the Arrenhius Law, with no condensed phase reaction. With this model, strong gas phase resonance has been found in certain cases at the characteristic gas-phase frequencies, but the peaking of the acoustic admittance is in the direction favoring the damping of pressure waves. At still higher frequencies, moderate wave-amplifying ability was found. The limit of low frequency response obtained previously by Denison and Baum was recovered, and the limitations of the quasi-steady theory were investigated.

  13. {HIGH Resolution Electronic Spectroscopy of 2,6-DIAMINOPYRIDINE in the Gas PHASE}

    NASA Astrophysics Data System (ADS)

    Clements, Casey L.; Fleisher, Adam J.; Young, Justin W.; Thomas, Jessica A.; Pratt, David W.

    2009-06-01

    Ab initio calculations suggest that 2,6-diaminopyridine (26DAP) has several interesting low-frequency vibrations arising from motion of its amino groups. For this reason, 26DAP has been studied in the gas phase using both low resolution and high resolution electronic spectroscopy techniques. Presented here are the results of this study, which provide information about the structural and dynamical properties of 26DAP in both the ground and excited electronic states. The results will be discussed. footnote

  14. PSS-SQL: protein secondary structure - structured query language.

    PubMed

    Mrozek, Dariusz; Wieczorek, Dominika; Malysiak-Mrozek, Bozena; Kozielski, Stanislaw

    2010-01-01

    Secondary structure representation of proteins provides important information regarding protein general construction and shape. This representation is often used in protein similarity searching. Since existing commercial database management systems do not offer integrated exploration methods for biological data e.g. at the level of the SQL language, the structural similarity searching is usually performed by external tools. In the paper, we present our newly developed PSS-SQL language, which allows searching a database in order to identify proteins having secondary structure similar to the structure specified by the user in a PSS-SQL query. Therefore, we provide a simple and declarative language for protein structure similarity searching.

  15. Constrained Peptides as Miniature Protein Structures

    PubMed Central

    Yin, Hang

    2012-01-01

    This paper discusses the recent developments of protein engineering using both covalent and noncovalent bonds to constrain peptides, forcing them into designed protein secondary structures. These constrained peptides subsequently can be used as peptidomimetics for biological functions such as regulations of protein-protein interactions. PMID:25969758

  16. Infrared Structural Biology: Detect Functionally Important Structural Motions of Proteins

    NASA Astrophysics Data System (ADS)

    Xie, Aihua

    Proteins are dynamic. Lack of dynamic structures of proteins hampers our understanding of protein functions. Infrared structural biology (IRSB) is an emerging technology. There are several advantages of IRSB for mechanistic studies of proteins: (1) its excellent dynamic range (detecting structural motions from picoseconds to >= seconds); (2) its high structural sensitivity (detect tiny but functionally important structural motions such as proton transfer and changes in hydrogen bonding interaction); (3) its ability to detect different structural motions simultaneously. Successful development of infrared structural biology demands not only new experimental techniques (from infrared technologies to chemical synthesis and cell biology), but also new data processing (how to translate infrared signals into quantitative structural information of proteins). These topics will be discussed as well as examples of how to use IRSB to study structure-function relationship of proteins. This work was supported by NSF DBI1338097 and OCAST HR10-078.

  17. Structural templates for comparative protein docking

    PubMed Central

    Anishchenko, Ivan; Kundrotas, Petras J.; Tuzikov, Alexander V.; Vakser, Ilya A.

    2014-01-01

    Structural characterization of protein-protein interactions is important for understanding life processes. Because of the inherent limitations of experimental techniques, such characterization requires computational approaches. Along with the traditional protein-protein docking (free search for a match between two proteins), comparative (template-based) modeling of protein-protein complexes has been gaining popularity. Its development puts an emphasis on full and partial structural similarity between the target protein monomers and the protein-protein complexes previously determined by experimental techniques (templates). The template-based docking relies on the quality and diversity of the template set. We present a carefully curated, non-redundant library of templates containing 4,950 full structures of binary complexes and 5,936 protein-protein interfaces extracted from the full structures at 12Å distance cut-off. Redundancy in the libraries was removed by clustering the PDB structures based on structural similarity. The value of the clustering threshold was determined from the analysis of the clusters and the docking performance on a benchmark set. High structural quality of the interfaces in the template and validation sets was achieved by automated procedures and manual curation. The library is included in the Dockground resource for molecular recognition studies at http://dockground.bioinformatics.ku.edu. PMID:25488330

  18. Structural templates for comparative protein docking.

    PubMed

    Anishchenko, Ivan; Kundrotas, Petras J; Tuzikov, Alexander V; Vakser, Ilya A

    2015-09-01

    Structural characterization of protein-protein interactions is important for understanding life processes. Because of the inherent limitations of experimental techniques, such characterization requires computational approaches. Along with the traditional protein-protein docking (free search for a match between two proteins), comparative (template-based) modeling of protein-protein complexes has been gaining popularity. Its development puts an emphasis on full and partial structural similarity between the target protein monomers and the protein-protein complexes previously determined by experimental techniques (templates). The template-based docking relies on the quality and diversity of the template set. We present a carefully curated, nonredundant library of templates containing 4950 full structures of binary complexes and 5936 protein-protein interfaces extracted from the full structures at 12 Å distance cut-off. Redundancy in the libraries was removed by clustering the PDB structures based on structural similarity. The value of the clustering threshold was determined from the analysis of the clusters and the docking performance on a benchmark set. High structural quality of the interfaces in the template and validation sets was achieved by automated procedures and manual curation. The library is included in the Dockground resource for molecular recognition studies at http://dockground.bioinformatics.ku.edu.

  19. Primary structures of two proteins from the venom of the Mexican red knee tarantula (Brachypelma smithii).

    PubMed

    Kaiser, I I; Griffin, P R; Aird, S D; Hudiburg, S; Shabanowitz, J; Francis, B; John, T R; Hunt, D F; Odell, G V

    1994-09-01

    Venom of the Mexican red knee tarantula (Brachypelma smithii) was fractionated by gel filtration over Sephadex G-50 Fine. Small polypeptides present in the second and third peaks were subfractionated by cation exchange and reversed-phase FPLC. One major, basic protein was isolated and sequenced from each G-50 fraction using a gas-phase protein sequencer. Primary structures were completed and confirmed using tandem mass spectrometry and carboxypeptidase digestions. Protein 1 contains 39 residues, including six cysteine residues in three disulfide bonds. It is identical to one of the isoforms of ESTX from the venom of the tarantula Eurypelma californicum. Brachypelma smithii Protein 5 contains 34 residues, including six cysteine residues in three disulfide bonds. Disulfide bond assignments for both proteins are provided. Protein 5 shows most similarity with toxin Tx2-9 from the Brazilian 'armed' spider, but only displays 41% sequence identity. Similarities with other proteins are lower. Proteins 1 and 5 appear unrelated to each other. PMID:7801344

  20. Insights into the structures of the gas-phase hydrated cations M⁺(H₂O)(n)Ar (M = Li, Na, K, Rb, and Cs; n = 3-5) using infrared photodissociation spectroscopy and thermodynamic analysis.

    PubMed

    Ke, Haochen; van der Linde, Christian; Lisy, James M

    2015-03-12

    The hydration of alkali cations yields a variety of structural conformers with varying numbers of water molecules in the first solvation shell. How these ions move from the aqueous phase into biological systems, such as at the entrance of an ion channel, depends on the interplay between competing intermolecular forces, which first must involve ion-water and water-water interactions. New infrared action spectra, using argon as a messenger or "spy", for Li(+), Na(+), and K(+), with up to five water molecules are reported, and new structural conformers determined from ab initio calculations, combined with previous results on Rb(+) and Cs(+), have identified structural transitions at each hydration level. These transitions are a result of the delicate balance between competing noncovalent interactions and represent a quantitative microscopic view of the macroscopic enthalpy-entropy competition between energy and structural variety. Smaller cations (Li(+) and Na(+)), with higher charge density, yield structural configurations with extended linear networks of hydrogen bonds. Larger cations (Rb(+) and Cs(+)), with lower charge density, generate configurations with cyclic hydrogen-bonded water subunits. It appears that K(+) is somewhat unique, with very simple (and predominantly) single structural conformers. This has led to the suggestion that K(+) can "move" easily in or through biological systems, concealing its identity as an ion, under the "appearance" or disguise of a water molecule. PMID:25651135

  1. The MULTICOM protein tertiary structure prediction system.

    PubMed

    Li, Jilong; Bhattacharya, Debswapna; Cao, Renzhi; Adhikari, Badri; Deng, Xin; Eickholt, Jesse; Cheng, Jianlin

    2014-01-01

    With the expansion of genomics and proteomics data aided by the rapid progress of next-generation sequencing technologies, computational prediction of protein three-dimensional structure is an essential part of modern structural genomics initiatives. Prediction of protein structure through understanding of the theories behind protein sequence-structure relationship, however, remains one of the most challenging problems in contemporary life sciences. Here, we describe MULTICOM, a multi-level combination technique, intended to predict moderate- to high-resolution structure of a protein through a novel approach of combining multiple sources of complementary information derived from the experimentally solved protein structures in the Protein Data Bank. The MULTICOM web server is freely available at http://sysbio.rnet.missouri.edu/multicom_toolbox/.

  2. Development of a gas-phase stereochemical protocol. Intrinsic diastereoselectivity in hydride reductions of cyclohexanones

    SciTech Connect

    Yeunghaw Ho; Squires, R.R. )

    1992-12-30

    A common feature of classical, intuitive models and modern molecular orbital-based theories for diastereoselectivity in ketone reduction reactions is an emphasis on the structural and electronic properties of the substrate, despite the fact that the stereochemical outcome of these reactions often displays marked sensitivity to the solvent and the type of counter-ion employed with ionic and polar reducing agents. One way to separate intrinsic and extrinsic effects on the stereochemistry of ketone reduction reactions is to examine them in the gas phase, where solvent and counterion effects are absent. The authors describe here an experimental method for distinguishing the diastereomeric products of gas-phase hydride reduction reactions, and its application in determining the intrinsic diastereoselectivity involved in reductions of alkyl-substituted cyclohexanones. 1 tab.

  3. Elusive Sulfurous Acid: Gas-Phase Basicity and IR Signature of the Protonated Species.

    PubMed

    Sinha, Rajeev K; Scuderi, Debora; Maitre, Philippe; Chiavarino, Barbara; Crestoni, Maria Elisa; Fornarini, Simonetta

    2015-05-01

    The ion corresponding to protonated sulfurous acid, H3SO3(+), has been successfully delivered into the gas phase by electrospray ionization of the solution of a suitable precursor and an in-source fragmentation process. The neutral acid is a highly elusive molecule. However, its gas-phase basicity has been ascertained by means of a kinetic study of proton-transfer reactivity. The structure of the H3SO3(+) sampled ion has been probed by IRMPD spectroscopy in two complementary IR frequency ranges in conjunction with density functional theory calculations and found to conform to a trihydroxosulfonium ion. The characteristic IR signatures may aid in deciphering the presence of this species in extraterrestrial atmospheres. PMID:26263321

  4. Elusive Sulfurous Acid: Gas-Phase Basicity and IR Signature of the Protonated Species.

    PubMed

    Sinha, Rajeev K; Scuderi, Debora; Maitre, Philippe; Chiavarino, Barbara; Crestoni, Maria Elisa; Fornarini, Simonetta

    2015-05-01

    The ion corresponding to protonated sulfurous acid, H3SO3(+), has been successfully delivered into the gas phase by electrospray ionization of the solution of a suitable precursor and an in-source fragmentation process. The neutral acid is a highly elusive molecule. However, its gas-phase basicity has been ascertained by means of a kinetic study of proton-transfer reactivity. The structure of the H3SO3(+) sampled ion has been probed by IRMPD spectroscopy in two complementary IR frequency ranges in conjunction with density functional theory calculations and found to conform to a trihydroxosulfonium ion. The characteristic IR signatures may aid in deciphering the presence of this species in extraterrestrial atmospheres.

  5. NAPS: Network Analysis of Protein Structures.

    PubMed

    Chakrabarty, Broto; Parekh, Nita

    2016-07-01

    Traditionally, protein structures have been analysed by the secondary structure architecture and fold arrangement. An alternative approach that has shown promise is modelling proteins as a network of non-covalent interactions between amino acid residues. The network representation of proteins provide a systems approach to topological analysis of complex three-dimensional structures irrespective of secondary structure and fold type and provide insights into structure-function relationship. We have developed a web server for network based analysis of protein structures, NAPS, that facilitates quantitative and qualitative (visual) analysis of residue-residue interactions in: single chains, protein complex, modelled protein structures and trajectories (e.g. from molecular dynamics simulations). The user can specify atom type for network construction, distance range (in Å) and minimal amino acid separation along the sequence. NAPS provides users selection of node(s) and its neighbourhood based on centrality measures, physicochemical properties of amino acids or cluster of well-connected residues (k-cliques) for further analysis. Visual analysis of interacting domains and protein chains, and shortest path lengths between pair of residues are additional features that aid in functional analysis. NAPS support various analyses and visualization views for identifying functional residues, provide insight into mechanisms of protein folding, domain-domain and protein-protein interactions for understanding communication within and between proteins. URL:http://bioinf.iiit.ac.in/NAPS/. PMID:27151201

  6. Protein structure prediction using hybrid AI methods

    SciTech Connect

    Guan, X.; Mural, R.J.; Uberbacher, E.C.

    1993-11-01

    This paper describes a new approach for predicting protein structures based on Artificial Intelligence methods and genetic algorithms. We combine nearest neighbor searching algorithms, neural networks, heuristic rules and genetic algorithms to form an integrated system to predict protein structures from their primary amino acid sequences. First we describe our methods and how they are integrated, and then apply our methods to several protein sequences. The results are very close to the real structures obtained by crystallography. Parallel genetic algorithms are also implemented.

  7. Gas-phase NMR studies of alcohols. Intrinsic acidities

    NASA Astrophysics Data System (ADS)

    Chauvel, J. Paul; True, Nancy S.

    1985-05-01

    Gas-phase (≈100 Torr) 1H NMR spectra of eighteen simple aliphatic and unsaturated alcohols, four fluorinated alcohols, and two thiols were obtained at 148.6°C where hydrogen bonding has little effect on chemical shifts. For the methanol, ethanol, n-propanol, i-propanol, t-butanol, i- butanol, neopentanol, 2,2,2-trifluoroethanol and benzyl alcohol, the observed hydroxylic proton chemical shifts correlate with previously obtained relative gas-phase acidities from thermochemical analysis which employed equilibrium constants of proton transfer reactions measured via mass spectroscopic and ion cyclotron resonance techniques. The correlational dependence is 10.3(0.5) kcal/mol ppm with a correlation coefficient of 0.99. These results demonstrate that the trend of increasing acidity with increasing size of the alkyl substituent is also reflected in the neutral forms of the alcohols, indicating that the polarizability of the ionic forms is not the only determining factor in relative gas-phase acidities of alcohols. Although factors affecting the hydroxylic proton chemical shifts of the larger substituted and unsaturated alcohols are more complex, their observed 1H NMR spectra also reflect this trend. For methanol and ethanol observed gas-phase 1H chemical shifts are also compared with recent theoritical calculations. 3JHH coupling constants across CO bonds are ≈ 5.5 Hz, significantly smaller than typical 3JHH coupling across sp 3 hybrid C C bonds.

  8. NMR study of stable radicals in the gas phase

    NASA Astrophysics Data System (ADS)

    Obynochny, A. A.; Maryasov, A. G.; Shakirov, M. M.; Grigoriev, I. A.

    1993-05-01

    The temperature dependence of the NMR spectrum of methyl-substituted nitroxyl radical of the imidazoline series has been studied. The NMR signal induced by radicals in the gas phase has been observed. A shift of the lines of the NMR spectrum in the gas phase according to the Curie law is observed which allows one to determine the value of the hfi constant of the protons of different racial groups. The hfi constant for methyl-substituted radical within experimental accuracy coincides with those measured by other methods in the liquid phase. In the absorbed phase of the samples under study, a substantial contribution is made by the volumetric susceptibility of the liquid film. The diamagnetic contribution to the magnetic susceptibility of the radical in the liquid state has been measured (in the film of 2 × 10 -6). When the thickness of the adsorbed film is small, the molecular exchange between the liquid and gas phases becomes noticeable, causing a corresponding additional shift of the lines. The gas-kinetic cross section for the radical (120 Å 2) has been estimated from the temperature dependence of the line width in the gas phase.

  9. INVESTIGATION OF GAS-PHASE OZONE AS A POTENTIAL BIOCIDE

    EPA Science Inventory

    The paper presents data on the effect of ozone on both vegetative and spore-forming fungi as well as on spore-forming bacteria. (NOTE: Despite the wide use of ozone generators in indoor air cleaning, there is little research data on ozone's biocidal activity in the gas phase.) Dr...

  10. Statistical and Microscopic Approach to Gas Phase Chemical Kinetics.

    ERIC Educational Resources Information Center

    Perez, J. M.; Quereda, R.

    1983-01-01

    Describes advanced undergraduate laboratory exercise examining the dependence of the rate constants and the instantaneous concentrations with the nature and energy content in a gas-phase complex reaction. Computer program (with instructions and computation flow charts) used with the exercise is available from the author. (Author/JN)

  11. Ion-Molecule Reactions in Gas Phase Radiation Chemistry.

    ERIC Educational Resources Information Center

    Willis, Clive

    1981-01-01

    Discusses some aspects of the radiation chemistry of gases, focusing on the ion-molecule and charge neutralization reactions which set study of the gas phase apart. Uses three examples that illustrate radiolysis, describing the radiolysis of (1) oxygen, (2) carbon dioxide, and (3) acetylene. (CS)

  12. Structural Studies of Protein-Surfactant Complexes

    SciTech Connect

    Chodankar, S. N.; Aswal, V. K.; Wagh, A. G.

    2008-03-17

    The structure of protein-surfactant complexes of two proteins bovine serum albumin (BSA) and lysozyme in presence of anionic surfactant sodium dodecyl sulfate (SDS) has been studied using small-angle neutron scattering (SANS). It is observed that these two proteins form different complex structures with the surfactant. While BSA protein undergoes unfolding on addition of surfactant, lysozyme does not show any unfolding even up to very high surfactant concentrations. The unfolding of BSA protein is caused by micelle-like aggregation of surfactant molecules in the complex. On the other hand, for lysozyme protein there is only binding of individual surfactant molecules to protein. Lysozyme in presence of higher surfactant concentrations has protein-surfactant complex structure coexisting with pure surfactant micelles.

  13. Structure of mutant human oncogene protein determined

    SciTech Connect

    Baum, R.

    1989-01-16

    The protein encoded by a mutant human oncogene differs only slightly in structure from the native protein that initiates normal cell division, a finding that may complicate efforts to develop inhibitors of the mutant protein. Previously, the x-ray structure of the protein encoded by the normal c-Ha-ras gene, a protein believed to signal cells to start or stop dividing through its interaction with guanosine triphosphate (GTP), was reported. The structure of the protein encoded by a transforming c-Ha-ras oncogene, in which a valine codon replaces the normal glycine codon at position 12 in the gene, has now been determined. The differences in the structures of the mutant and normal proteins are located primarily in a loop that interacts with the /beta/-phosphate of a bound guanosine diphosphate (GDP) molecule.

  14. Comparative Protein Structure Modeling Using MODELLER.

    PubMed

    Webb, Benjamin; Sali, Andrej

    2014-09-08

    Functional characterization of a protein sequence is one of the most frequent problems in biology. This task is usually facilitated by accurate three-dimensional (3-D) structure of the studied protein. In the absence of an experimentally determined structure, comparative or homology modeling can sometimes provide a useful 3-D model for a protein that is related to at least one known protein structure. Comparative modeling predicts the 3-D structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates). The prediction process consists of fold assignment, target-template alignment, model building, and model evaluation. This unit describes how to calculate comparative models using the program MODELLER and discusses all four steps of comparative modeling, frequently observed errors, and some applications. Modeling lactate dehydrogenase from Trichomonas vaginalis (TvLDH) is described as an example. The download and installation of the MODELLER software is also described.

  15. NAPS: Network Analysis of Protein Structures

    PubMed Central

    Chakrabarty, Broto; Parekh, Nita

    2016-01-01

    Traditionally, protein structures have been analysed by the secondary structure architecture and fold arrangement. An alternative approach that has shown promise is modelling proteins as a network of non-covalent interactions between amino acid residues. The network representation of proteins provide a systems approach to topological analysis of complex three-dimensional structures irrespective of secondary structure and fold type and provide insights into structure-function relationship. We have developed a web server for network based analysis of protein structures, NAPS, that facilitates quantitative and qualitative (visual) analysis of residue–residue interactions in: single chains, protein complex, modelled protein structures and trajectories (e.g. from molecular dynamics simulations). The user can specify atom type for network construction, distance range (in Å) and minimal amino acid separation along the sequence. NAPS provides users selection of node(s) and its neighbourhood based on centrality measures, physicochemical properties of amino acids or cluster of well-connected residues (k-cliques) for further analysis. Visual analysis of interacting domains and protein chains, and shortest path lengths between pair of residues are additional features that aid in functional analysis. NAPS support various analyses and visualization views for identifying functional residues, provide insight into mechanisms of protein folding, domain-domain and protein–protein interactions for understanding communication within and between proteins. URL:http://bioinf.iiit.ac.in/NAPS/. PMID:27151201

  16. Protein knot server: detection of knots in protein structures.

    PubMed

    Kolesov, Grigory; Virnau, Peter; Kardar, Mehran; Mirny, Leonid A

    2007-07-01

    KNOTS (http://knots.mit.edu) is a web server that detects knots in protein structures. Several protein structures have been reported to contain intricate knots. The physiological role of knots and their effect on folding and evolution is an area of active research. The user submits a PDB id or uploads a 3D protein structure in PDB or mmCIF format. The current implementation of the server uses the Alexander polynomial to detect knots. The results of the analysis that are presented to the user are the location of the knot in the structure, the type of the knot and an interactive visualization of the knot. The results can also be downloaded and viewed offline. The server also maintains a regularly updated list of known knots in protein structures.

  17. Structural classification of proteins and structural genomics: new insights into protein folding and evolution

    PubMed Central

    Andreeva, Antonina; Murzin, Alexey G.

    2010-01-01

    During the past decade, the Protein Structure Initiative (PSI) centres have become major contributors of new families, superfamilies and folds to the Structural Classification of Proteins (SCOP) database. The PSI results have increased the diversity of protein structural space and accelerated our understanding of it. This review article surveys a selection of protein structures determined by the Joint Center for Structural Genomics (JCSG). It presents previously undescribed β-sheet architectures such as the double barrel and spiral β-roll and discusses new examples of unusual topologies and peculiar structural features observed in proteins characterized by the JCSG and other Structural Genomics centres. PMID:20944210

  18. A new protein structure representation for efficient protein function prediction.

    PubMed

    Maghawry, Huda A; Mostafa, Mostafa G M; Gharib, Tarek F

    2014-12-01

    One of the challenging problems in bioinformatics is the prediction of protein function. Protein function is the main key that can be used to classify different proteins. Protein function can be inferred experimentally with very small throughput or computationally with very high throughput. Computational methods are sequence based or structure based. Structure-based methods produce more accurate protein function prediction. In this article, we propose a new protein structure representation for efficient protein function prediction. The representation is based on three-dimensional patterns of protein residues. In the analysis, we used protein function based on enzyme activity through six mechanistically diverse enzyme superfamilies: amidohydrolase, crotonase, haloacid dehalogenase, isoprenoid synthase type I, and vicinal oxygen chelate. We applied three different classification methods, naïve Bayes, k-nearest neighbors, and random forest, to predict the enzyme superfamily of a given protein. The prediction accuracy using the proposed representation outperforms a recently introduced representation method that is based only on the distance patterns. The results show that the proposed representation achieved prediction accuracy up to 98%, with improvement of about 10% on average.

  19. Predicting protein dynamics from structural ensembles

    NASA Astrophysics Data System (ADS)

    Copperman, J.; Guenza, M. G.

    2015-12-01

    The biological properties of proteins are uniquely determined by their structure and dynamics. A protein in solution populates a structural ensemble of metastable configurations around the global fold. From overall rotation to local fluctuations, the dynamics of proteins can cover several orders of magnitude in time scales. We propose a simulation-free coarse-grained approach which utilizes knowledge of the important metastable folded states of the protein to predict the protein dynamics. This approach is based upon the Langevin Equation for Protein Dynamics (LE4PD), a Langevin formalism in the coordinates of the protein backbone. The linear modes of this Langevin formalism organize the fluctuations of the protein, so that more extended dynamical cooperativity relates to increasing energy barriers to mode diffusion. The accuracy of the LE4PD is verified by analyzing the predicted dynamics across a set of seven different proteins for which both relaxation data and NMR solution structures are available. Using experimental NMR conformers as the input structural ensembles, LE4PD predicts quantitatively accurate results, with correlation coefficient ρ = 0.93 to NMR backbone relaxation measurements for the seven proteins. The NMR solution structure derived ensemble and predicted dynamical relaxation is compared with molecular dynamics simulation-derived structural ensembles and LE4PD predictions and is consistent in the time scale of the simulations. The use of the experimental NMR conformers frees the approach from computationally demanding simulations.

  20. Protein Structures Revealed at Record Pace

    SciTech Connect

    Hura, Greg

    2009-01-01

    The structure of a protein in days -- not months or years -- ushers in a new era in genomics research. Berkeley Lab scientists have developed a high-throughput protein pipeline that could expedite the development of biofuels and elucidate how proteins carry out lifes vital functions.

  1. Protein Structures Revealed at Record Pace

    SciTech Connect

    Greg Hura

    2009-07-09

    The structure of a protein in days -- not months or years -- ushers in a new era in genomics research. Berkeley Lab scientists have developed a high-throughput protein pipeline that could expedite the development of biofuels and elucidate how proteins carry out lifes vital functions.

  2. Protein Structures Revealed at Record Pace

    ScienceCinema

    Hura, Greg

    2013-05-29

    The structure of a protein in days -- not months or years -- ushers in a new era in genomics research. Berkeley Lab scientists have developed a high-throughput protein pipeline that could expedite the development of biofuels and elucidate how proteins carry out lifes vital functions.

  3. Protein Structures Revealed at Record Pace

    ScienceCinema

    Greg Hura

    2016-07-12

    The structure of a protein in days -- not months or years -- ushers in a new era in genomics research. Berkeley Lab scientists have developed a high-throughput protein pipeline that could expedite the development of biofuels and elucidate how proteins carry out lifes vital functions.

  4. The Decomposition of Hydrazine in the Gas Phase and over an Iridium Catalyst

    SciTech Connect

    Schmidt, Michael W.; Gordon, Mark S.

    2013-09-30

    Hydrazine is an important rocket fuel, used as both a monopropellant and a bipropellant. This paper presents theoretical results to complement the extensive experimental studies of the gas phase and Ir catalyzed decompositions involved in the monopropellant applications of hydrazine. Gas phase electronic structure theory calculations that include electron correlation predict that numerous molecular and free radical reactions occur within the same energy range as the basic free radical pathways: NN bond breaking around 65 kcal/mol and NH bond breaking around 81 kcal/mol. The data suggest that a revision to existing kinetics modeling is desirable, based on the energetics and the new elementary steps reported herein. A supported Ir-6 octahedron model for the Shell 405 Iridium catalyst used in thrusters was developed. Self-Consistent Field and electron correlation calculations (with core potentials and associated basis sets) find a rich chemistry for hydrazine on this catalyst model. The model catalyst provides dramatically lower NN and NH bond cleavage energies and an even smaller barrier to breaking the NH bond by NH2 abstractions. Thus, the low temperature decomposition over the catalyst is interpreted in terms of consecutive NH2 abstractions to produce ammonia and nitrogen. The higher temperature channel, which has hydrogen and nitrogen products, may be due to a mixture of two mechanisms. These two mechanisms are successive NH cleavages with surface H + H recombinations, and the same type of assisted H-2 eliminations found to occur in the gas phase part of this study.

  5. Gas-Phase Photoluminescence Characterization of Stoichiometrically Pure Nonanuclear Lanthanoid Hydroxo Complexes Comprising Europium or Gadolinium.

    PubMed

    Greisch, Jean-François; Chmela, Jiří; Harding, Michael E; Klopper, Wim; Kappes, Manfred M; Schooss, Detlef

    2016-04-01

    Gas-phase photoluminescence measurements involving mass-spectrometric techniques enable determination of the properties of selected molecular systems with knowledge of their exact composition and unaffected by matrix effects such as solvent interactions or crystal packing. The resulting reduced complexity facilitates a comparison with theory. Herein, we provide a detailed report of the intrinsic luminescence properties of nonanuclear europium(III) and gadolinium(III) 9-hydroxyphenalen-1-one (HPLN) hydroxo complexes. Luminescence spectra of [Eu9(PLN)16(OH)10](+) ions reveal an europium-centered emission dominated by a 4-fold split Eu(III) hypersensitive transition, while photoluminescence lifetime measurements for both complexes support an efficient europium sensitization via a PLN-centered triplet-state manifold. The combination of gas-phase measurements with density functional theory computations and ligand-field theory is used to discuss the antiprismatic core structure of the complexes and to shed light on the energy-transfer mechanism. This methodology is also employed to fit a new set of parameters, which improves the accuracy of ligand-field computations of Eu(III) electronic transitions for gas-phase species. PMID:26974169

  6. Mass Spectrometry of Protein Complexes: From Origins to Applications

    NASA Astrophysics Data System (ADS)

    Mehmood, Shahid; Allison, Timothy M.; Robinson, Carol V.

    2015-04-01

    Now routine is the ability to investigate soluble and membrane protein complexes in the gas phase of a mass spectrometer while preserving folded structure and ligand-binding properties. Several recent transformative developments have occurred to arrive at this point. These include advances in mass spectrometry instrumentation, particularly with respect to resolution; the ability to study intact membrane protein complexes released from detergent micelles; and the use of protein unfolding in the gas phase to obtain stability parameters. Together, these discoveries are providing unprecedented information on the compositional heterogeneity of biomacromolecules, the unfolding trajectories of multidomain proteins, and the stability imparted by ligand binding to both soluble and membrane-embedded protein complexes. We review these recent breakthroughs, highlighting the challenges that had to be overcome and the physicochemical insight that can now be gained from studying proteins and their assemblies in the gas phase.

  7. Genome-wide Membrane Protein Structure Prediction

    PubMed Central

    Piccoli, Stefano; Suku, Eda; Garonzi, Marianna; Giorgetti, Alejandro

    2013-01-01

    Transmembrane proteins allow cells to extensively communicate with the external world in a very accurate and specific way. They form principal nodes in several signaling pathways and attract large interest in therapeutic intervention, as the majority pharmaceutical compounds target membrane proteins. Thus, according to the current genome annotation methods, a detailed structural/functional characterization at the protein level of each of the elements codified in the genome is also required. The extreme difficulty in obtaining high-resolution three-dimensional structures, calls for computational approaches. Here we review to which extent the efforts made in the last few years, combining the structural characterization of membrane proteins with protein bioinformatics techniques, could help describing membrane proteins at a genome-wide scale. In particular we analyze the use of comparative modeling techniques as a way of overcoming the lack of high-resolution three-dimensional structures in the human membrane proteome. PMID:24403851

  8. Website on Protein Interaction and Protein Structure Related Work

    NASA Technical Reports Server (NTRS)

    Samanta, Manoj; Liang, Shoudan; Biegel, Bryan (Technical Monitor)

    2003-01-01

    In today's world, three seemingly diverse fields - computer information technology, nanotechnology and biotechnology are joining forces to enlarge our scientific knowledge and solve complex technological problems. Our group is dedicated to conduct theoretical research exploring the challenges in this area. The major areas of research include: 1) Yeast Protein Interactions; 2) Protein Structures; and 3) Current Transport through Small Molecules.

  9. Advances in Homology Protein Structure Modeling

    PubMed Central

    Xiang, Zhexin

    2007-01-01

    Homology modeling plays a central role in determining protein structure in the structural genomics project. The importance of homology modeling has been steadily increasing because of the large gap that exists between the overwhelming number of available protein sequences and experimentally solved protein structures, and also, more importantly, because of the increasing reliability and accuracy of the method. In fact, a protein sequence with over 30% identity to a known structure can often be predicted with an accuracy equivalent to a low-resolution X-ray structure. The recent advances in homology modeling, especially in detecting distant homologues, aligning sequences with template structures, modeling of loops and side chains, as well as detecting errors in a model, have contributed to reliable prediction of protein structure, which was not possible even several years ago. The ongoing efforts in solving protein structures, which can be time-consuming and often difficult, will continue to spur the development of a host of new computational methods that can fill in the gap and further contribute to understanding the relationship between protein structure and function. PMID:16787261

  10. The molecular structure of TbI 3, DyI 3, HoI 3 and ErI 3 as determined by synchronous gas-phase electron diffraction and mass spectrometric experiment assisted by quantum chemical calculations

    NASA Astrophysics Data System (ADS)

    Shlykov, Sergey A.; Giricheva, Nina I.; Lapykina, Elena A.; Girichev, Georgiy V.; Oberhammer, Heinz

    2010-08-01

    A first gas electron diffraction study of TbI 3, DyI 3, HoI 3 and ErI 3 has been carried out in combination with mass spectrometric vapour monitoring at 1117(10), 1117(10), 1132(10) and 1102(10) K, respectively. Up to 4 mol.% of dimeric species was observed in addition to the dominating monomeric molecules. The change of the thermal-averaged rg-configuration parameters of the molecules in the series TbI 3 → ErI 3 reflect the lanthanide contraction. A low value of the shrinkage δ(I…I) even at such a high temperatures may be considered due to vibration effects in molecule whose equilibrium geometric nuclear structure is planar and which correspond to configurationally-averaged 4f n electronic state. B3LYP and МР2 calculations performed in this work with large core potential for lanthanide atoms also resulted in equilibrium geometry of D 3h symmetry. According to the both quantum chemical methods applied the potential function the non-planar vibration is essentially anharmonic, which is therefore to be taken into account to correctly describe nuclear dynamics in molecules such as LnI 3. Different models applied in this study predict the equilibrium distance re(Ln-I) to be shorter than the thermal-averaged rg(Ln-I) distance by 0.002-0.018(1) Å.

  11. Stabilizing factors of the molecular structure in silicon-based peptidomimetics in gas-phase and water solution. Assessment of the correlation between different descriptors of hydrogen bond strength.

    PubMed

    Rodríguez Ortega, María Pilar Gema; Montejo, Manuel; López González, Juan Jesús

    2013-10-01

    The use of DFT (B3LYP and M06L) and ab initio (MP2) computational methods allowed us to perform a thorough conformational study of N-[dihydroxy (methyl)silyl]methylformamide (DHSF) and 3-[dihydroxy (methyl) silyl] propanamide (DHSP), that could be considered simplified models of the environment of the silanediol group in silicon gem-diols that have proven efficiency as protease inhibitors. We have found a total of 13 molecular conformations that represent minima in the potential energy surfaces of DHSF (six conformers) and DHSP (seven conformers). The key feature in their molecular structure is the occurrence of intramolecular hydrogen bonding between the hydroxyl and aminocarbonyl groups. We have estimated the strength of each individual hydrogen bond in the mentioned species using the descriptors proposed by three different methodologies, i.e., the quantum theory of atoms in molecules (QTAIM), the natural bond orbitals population analysis (NBO), and the so-called empirical Rozenberg's enthalpy-distance relationship. We have found a good correlation among the calculated values for the different descriptors within the whole set of conformers in the molecular systems in this study. We have also discussed the predicted order of stabilities of the different conformers of each species in terms of the so-called ring anomeric effect (RAE) and generalized anomeric effect (GAE). Finally, we also analyzed the discrepancies found in the order of stability when going from the isolated molecule approximation to water solution (PCM).

  12. The effect of denaturants on protein structure.

    PubMed Central

    Dunbar, J.; Yennawar, H. P.; Banerjee, S.; Luo, J.; Farber, G. K.

    1997-01-01

    Virtually all studies of the protein-folding reaction add either heat, acid, or a chemical denaturant to an aqueous protein solution in order to perturb the protein structure. When chemical denaturants are used, very high concentrations are usually necessary to observe any change in protein structure. In a solution with such high denaturant concentrations, both the structure of the protein and the structure of the solvent around the protein can be altered. X-ray crystallography is the obvious experimental technique to probe both types of changes. In this paper, we report the crystal structures of dihydrofolate reductase with urea and of ribonuclease A with guanidinium chloride. These two classic denaturants have similar effects on the native structure of the protein. The most important change that occurs is a reduction in the overall thermal factor. These structures offer a molecular explanation for the reduction in mobility. Although the reduction is observed only with the native enzyme in the crystal, a similar decrease in mobility has also been observed in the unfolded state in solution (Makhatadze G, Privalov PL. 1992. Protein interactions with urea and guanidinium chloride: A calorimetric study. PMID:9260285

  13. PSSweb: protein structural statistics web server.

    PubMed

    Gaillard, Thomas; Stote, Roland H; Dejaegere, Annick

    2016-07-01

    With the increasing number of protein structures available, there is a need for tools capable of automating the comparison of ensembles of structures, a common requirement in structural biology and bioinformatics. PSSweb is a web server for protein structural statistics. It takes as input an ensemble of PDB files of protein structures, performs a multiple sequence alignment and computes structural statistics for each position of the alignment. Different optional functionalities are proposed: structure superposition, Cartesian coordinate statistics, dihedral angle calculation and statistics, and a cluster analysis based on dihedral angles. An interactive report is generated, containing a summary of the results, tables, figures and 3D visualization of superposed structures. The server is available at http://pssweb.org.

  14. PSSweb: protein structural statistics web server

    PubMed Central

    Gaillard, Thomas; Stote, Roland H.; Dejaegere, Annick

    2016-01-01

    With the increasing number of protein structures available, there is a need for tools capable of automating the comparison of ensembles of structures, a common requirement in structural biology and bioinformatics. PSSweb is a web server for protein structural statistics. It takes as input an ensemble of PDB files of protein structures, performs a multiple sequence alignment and computes structural statistics for each position of the alignment. Different optional functionalities are proposed: structure superposition, Cartesian coordinate statistics, dihedral angle calculation and statistics, and a cluster analysis based on dihedral angles. An interactive report is generated, containing a summary of the results, tables, figures and 3D visualization of superposed structures. The server is available at http://pssweb.org. PMID:27174930

  15. How membrane surface affects protein structure.

    PubMed

    Bychkova, V E; Basova, L V; Balobanov, V A

    2014-12-01

    The immediate environment of the negatively charged membrane surface is characterized by decreased dielectric constant and pH value. These conditions can be modeled by water-alcohol mixtures at moderately low pH. Several globular proteins were investigated under these conditions, and their conformational behavior in the presence of phospholipid membranes was determined, as well as under conditions modeling the immediate environment of the membrane surface. These proteins underwent conformational transitions from the native to a molten globule-like state. Increased flexibility of the protein structure facilitated protein functioning. Our experimental data allow understanding forces that affect the structure of a protein functioning near the membrane surface (in other words, in the membrane field). Similar conformational states are widely reported in the literature. This indicates that the negatively charged membrane surface can serve as a moderately denaturing agent in the cell. We conclude that the effect of the membrane field on the protein structure must be taken into account.

  16. Protein Structure Determination Using Protein Threading and Sparse NMR Data

    SciTech Connect

    Crawford, O.H.; Einstein, J.R.; Xu, D.; Xu, Y.

    1999-11-14

    It is well known that the NMR method for protein structure determination applies to small proteins and that its effectiveness decreases very rapidly as the molecular weight increases beyond about 30 kD. We have recently developed a method for protein structure determination that can fully utilize partial NMR data as calculation constraints. The core of the method is a threading algorithm that guarantees to find a globally optimal alignment between a query sequence and a template structure, under distance constraints specified by NMR/NOE data. Our preliminary tests have demonstrated that a small number of NMR/NOE distance restraints can significantly improve threading performance in both fold recognition and threading-alignment accuracy, and can possibly extend threading's scope of applicability from structural homologs to structural analogs. An accurate backbone structure generated by NMR-constrained threading can then provide a significant amount of structural information, equivalent to that provided by the NMR method with many NMR/NOE restraints; and hence can greatly reduce the amount of NMR data typically required for accurate structure determination. Our preliminary study suggests that a small number of NMR/NOE restraints may suffice to determine adequately the all-atom structure when those restraints are incorporated in a procedure combining threading, modeling of loops and sidechains, and molecular dynamics simulation. Potentially, this new technique can expand NMR's capability to larger proteins.

  17. Modeling mitochondrial protein evolution using structural information.

    PubMed

    Liò, Pietro; Goldman, Nick

    2002-04-01

    We present two new models of protein sequence evolution based on structural properties of mitochondrial proteins. We compare these models with others currently used in phylogenetic analyses, investigating their performance over both short and long evolutionary distances. We find that our models that incorporate secondary structure information from mitochondrial proteins are statistically comparable with existing models when studying 13 mitochondrial protein data sets from eutherian mammals. However, our models give a significantly improved description of the evolutionary process when used with 12 mitochondrial proteins from a broader range of organisms including fungi, plants, protists, and bacteria. Our models may thus be of use in estimating mitochondrial protein phylogenies and for the study of processes of mitochondrial protein evolution, in particular for distantly related organisms.

  18. Mapping membrane protein structure with fluorescence

    PubMed Central

    Taraska, Justin W.

    2012-01-01

    Membrane proteins regulate many cellular processes including signaling cascades, ion transport, membrane fusion, and cell-to-cell communications. Understanding the architecture and conformational fluctuations of these proteins is critical to understanding their regulation and functions. Fluorescence methods including intensity mapping, fluorescence resonance energy transfer, and photo-induced electron transfer, allow for targeted measurements of domains within membrane proteins. These methods can reveal how a protein is structured and how it transitions between different conformational states. Here, I will review recent work done using fluorescence to map the structures of membrane proteins, focusing on how each of these methods can be applied to understanding the dynamic nature of individual membrane proteins and protein complexes. PMID:22445227

  19. Gas Phase Reactivity of Carboxylates with N-Hydroxysuccinimide Esters

    NASA Astrophysics Data System (ADS)

    Peng, Zhou; McGee, William M.; Bu, Jiexun; Barefoot, Nathan Z.; McLuckey, Scott A.

    2015-01-01

    N-hydroxysuccinimide (NHS) esters have been used for gas-phase conjugation reactions with peptides at nucleophilic sites, such as primary amines (N-terminus, ɛ-amine of lysine) or guanidines, by forming amide bonds through a nucleophilic attack on the carbonyl carbon. The carboxylate has recently been found to also be a reactive nucleophile capable of initiating a similar nucleophilic attack to form a labile anhydride bond. The fragile bond is easily cleaved, resulting in an oxygen transfer from the carboxylate-containing species to the reagent, nominally observed as a water transfer. This reactivity is shown for both peptides and non-peptidic species. Reagents isotopically labeled with O18 were used to confirm reactivity. This constitutes an example of distinct differences in reactivity of carboxylates between the gas phase, where they are shown to be reactive, and the solution phase, where they are not regarded as reactive with NHS esters.

  20. Para-Hydrogen-Enhanced Gas-Phase Magnetic Resonance Imaging

    SciTech Connect

    Bouchard, Louis-S.; Kovtunov, Kirill V.; Burt, Scott R.; Anwar,M. Sabieh; Koptyug, Igor V.; Sagdeev, Renad Z.; Pines, Alexander

    2007-02-23

    Herein, we demonstrate magnetic resonance imaging (MRI) inthe gas phase using para-hydrogen (p-H2)-induced polarization. A reactantmixture of H2 enriched in the paraspin state and propylene gas is flowedthrough a reactor cell containing a heterogenized catalyst, Wilkinson'scatalyst immobilized on modified silica gel. The hydrogenation product,propane gas, is transferred to the NMR magnet and is spin-polarized as aresult of the ALTADENA (adiabatic longitudinal transport and dissociationengenders net alignment) effect. A polarization enhancement factor of 300relative to thermally polarized gas was observed in 1D1H NMR spectra.Enhancement was also evident in the magnetic resonance images. This isthe first demonstration of imaging a hyperpolarized gaseous productformed in a hydrogenation reaction catalyzed by a supported catalyst.This result may lead to several important applications, includingflow-through porous materials, gas-phase reaction kinetics and adsorptionstudies, and MRI in low fields, all using catalyst-free polarizedfluids.

  1. Ionization of vitamin C in gas phase: Theoretical study.

    PubMed

    Abyar, Fatemeh; Farrokhpour, Hossein

    2016-07-01

    In this work, the gas phase ionization energies and photoelectron spectra of four important conformers of vitamin C were calculated. Symmetry adapted cluster/configuration interaction methodology employing the single and double excitation operators (SAC-CI SD-R) along with D95++(d,p) basis set were used for the calculations. Thermochemistry calculations were also performed on all possible conformers of vitamin C to find the relative stability of conformers in the gas phase. The calculated ionization bands of each conformer were assigned by calculating the contribution of natural bonding orbital (NBO) in the calculated canonical molecular orbitals involved in the ionization. SAC-CI calculations showed that the first ionization band of vitamin C is related to the π electrons of CC bond of the ring of molecule although, there is the lone electron pairs of oxygen atoms and π electrons of CO bond in the molecule. PMID:27092998

  2. Gas-Phase Studies of Formamidopyrimidine Glycosylase (Fpg) Substrates.

    PubMed

    Kiruba, G S M; Xu, Jiahui; Zelikson, Victoria; Lee, Jeehiun K

    2016-03-01

    Gas-phase thermochemical properties (tautomerism, acidity, and proton affinity) have been measured and calculated for a series of nucleobase derivatives that have not heretofore been examined under vacuum. The studied species are substrates for the enzyme formamidopyrimidine glycosylase (Fpg), which cleaves damaged nucleobases from DNA. The gas-phase results are compared and contrasted to solution-phase data, to afford insight into the Fpg mechanism. Calculations are also used to probe the energetics of various possible mechanisms and to predict isotope effects that could potentially allow for discrimination between different mechanisms. Specifically, (18) O substitution at the ribose O4' is predicted to result in a normal kinetic isotope effect (KIE) for a ring-opening "endocyclic" mechanism and an inverse KIE for a direct base excision "exocyclic" pathway.

  3. Gas-Phase Studies of Formamidopyrimidine Glycosylase (Fpg) Substrates.

    PubMed

    Kiruba, G S M; Xu, Jiahui; Zelikson, Victoria; Lee, Jeehiun K

    2016-03-01

    Gas-phase thermochemical properties (tautomerism, acidity, and proton affinity) have been measured and calculated for a series of nucleobase derivatives that have not heretofore been examined under vacuum. The studied species are substrates for the enzyme formamidopyrimidine glycosylase (Fpg), which cleaves damaged nucleobases from DNA. The gas-phase results are compared and contrasted to solution-phase data, to afford insight into the Fpg mechanism. Calculations are also used to probe the energetics of various possible mechanisms and to predict isotope effects that could potentially allow for discrimination between different mechanisms. Specifically, (18) O substitution at the ribose O4' is predicted to result in a normal kinetic isotope effect (KIE) for a ring-opening "endocyclic" mechanism and an inverse KIE for a direct base excision "exocyclic" pathway. PMID:26894440

  4. Spectroscopic studies of cold, gas-phase biomolecular ions

    NASA Astrophysics Data System (ADS)

    Rizzo, Thomas R.; Stearns, Jaime A.; Boyarkin, Oleg V.

    While the marriage of mass spectrometry and laser spectroscopy is not new, developments over the last few years in this relationship have opened up new horizons for the spectroscopic study of biological molecules. The combination of electrospray ionisation for producing large biological molecules in the gas phase together with cooled ion traps and multiple-resonance laser schemes are allowing spectroscopic investigation of individual conformations of peptides with more than a dozen amino acids. Highly resolved infrared spectra of single conformations of such species provide important benchmarks for testing the accuracy of theoretical calculations. This review presents a number of techniques employed in our laboratory and in others for measuring the spectroscopy of cold, gas-phase protonated peptides. We show examples that demonstrate the power of these techniques and evaluate their extension to still larger biological molecules.

  5. Gas Phase Reactivity of Carboxylates with N-Hydroxysuccinimide Esters

    PubMed Central

    Peng, Zhou; McGee, William M.; Bu, Jiexun; Barefoot, Nathan Z.; McLuckey, Scott A.

    2015-01-01

    N-hydroxysuccinimide (NHS) esters have been used for gas phase conjugation reactions with peptides at nucleophilic sites, such as primary amines (N-terminus, ε-amine of lysine) or guanidines, by forming amide bonds through a nucleophilic attack on the carbonyl carbon. The carboxylate has recently been found to also be a reactive nucleophile capable of initiating a similar nucleophilic attack to form a labile anhydride bond. The fragile bond is easily cleaved, resulting in an oxygen transfer from the carboxylate-containing species to the reagent, nominally observed as a water transfer. This reactivity is shown for both peptides and non-peptidic species. Reagents isotopically labeled with O18 were used to confirm reactivity. This constitutes an example of distinct differences in reactivity of carboxylates between the gas-phase, where they are shown to be reactive, and the solution-phase, where they are not regarded as reactive with NHS esters. PMID:25338221

  6. Homology-Based Modeling of Protein Structure

    NASA Astrophysics Data System (ADS)

    Xiang, Zhexin

    The human genome project has already discovered millions of proteins (http://www.swissprot.com). The potential of the genome project can only be fully realized once we can assign, understand, manipulate, and predict the function of these new proteins (Sanchez and Sali, 1997; Frishman et al., 2000; Domingues et al., 2000). Predicting protein function generally requires knowledge of protein three-dimensional structure (Blundell et al., 1978;Weber, 1990), which is ultimately determined by protein sequence (Anfinsen, 1973). Protein structure determination using experimental methods such as X-ray crystallography or NMR spectroscopy is very time consuming (Johnson et al. 1994). To date, fewer than 2% of the known proteins have had their structures solved experimentally. In 2004, more than half a million new proteins were sequenced that almost doubled the efforts in the previous year, but only 5300 structures were solved. Although the rate of experimental structure determination will continue to increase, the number of newly discovered sequences grows much faster than the number of structures solved (see Fig. 10.1).

  7. Lessons from making the Structural Classification of Proteins (SCOP) and their implications for protein structure modelling

    PubMed Central

    Andreeva, Antonina

    2016-01-01

    The Structural Classification of Proteins (SCOP) database has facilitated the development of many tools and algorithms and it has been successfully used in protein structure prediction and large-scale genome annotations. During the development of SCOP, numerous exceptions were found to topological rules, along with complex evolutionary scenarios and peculiarities in proteins including the ability to fold into alternative structures. This article reviews cases of structural variations observed for individual proteins and among groups of homologues, knowledge of which is essential for protein structure modelling. PMID:27284063

  8. Modeling Protein Aggregate Assembly and Structure

    NASA Astrophysics Data System (ADS)

    Guo, Jun-tao; Hall, Carol K.; Xu, Ying; Wetzel, Ronald

    One might say that "protein science" got its start in the domestic arts, built around the abilities of proteins to aggregate in response to environmental stresses such as heating (boiled eggs), heating and cooling (gelatin), and pH (cheese). Characterization of proteins in the late nineteenth century likewise focused on the ability of proteins to precipitate in response to certain salts and to aggregate in response to heating. Investigations by Chick and Martin (Chick and Martin, 1910) showed that the inactivating response of proteins to heat or solvent treatment is a two-step process involving separate denaturation and precipitation steps. Monitoring the coagulation and flocculation responses of proteins to heat and other stresses remained a major approach to understanding protein structure for decades, with solubility, or susceptibility to aggregation, serving as a kind of benchmark against which results of other methods, such as viscosity, chemical susceptibility, immune activity, crystallizability, and susceptibility to proteolysis, were compared (Mirsky and Pauling, 1936;Wu, 1931). Toward the middle of the last century, protein aggregation studies were largely left behind, as improved methods allowed elucidation of the primary sequence of proteins, reversible unfolding studies, and ultimately high-resolution structures. Curiously, the field of protein science, and in particular protein folding, is now gravitating back to a closer look at protein aggregation and protein aggregates. Unfortunately, the means developed during the second half of the twentieth century for studying native, globular proteins have not proved immediately amenable to the study of aggregate structures. Great progress is being made, however, to modify classical methods, including NMR and X-ray diffraction, as well as to develop newer techniques, that together should continue to expand our picture of aggregate structure (Kheterpal and Wetzel, 2006; Wetzel, 1999).

  9. Measuring Uptake Coefficients and Henry's Law Constants of Gas-Phase Species with Models for Secondary Organic Aerosol

    NASA Astrophysics Data System (ADS)

    Fairhurst, M. C.; Waring-Kidd, C.; Ezell, M. J.; Finlayson-Pitts, B. J.

    2014-12-01

    Volatile organic compounds (VOC) are oxidized in the atmosphere and their products contribute to secondary organic aerosol (SOA) formation. These particles have been shown to have effects on visibility, climate, and human health. Current models typically under-predict SOA concentrations from field measurements. Underestimation of these concentrations could be a result of how models treat particle growth. It is often assumed that particles grow via instantaneous thermal equilibrium partitioning between liquid particles and gas-phase species. Recent work has shown that growth may be better represented by irreversible, kinetically limited uptake of gas-phase species onto more viscous, tar-like SOA. However, uptake coefficients for these processes are not known. The goal of this project is to measure uptake coefficients and solubilities for different gases onto models serving as proxies for SOA and determine how they vary based on the chemical composition of the gas and the condensed phase. Experiments were conducted using two approaches: attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and a flow system coupled to a mass spectrometer. The ATR crystal was coated with the SOA proxy and the gas-phase species introduced via a custom flow system. Uptake of the gas-phase species was characterized by measuring the intensity of characteristic IR bands as a function of time, from which a Henry's law constant and initial estimate of uptake coefficients could be obtained. Uptake coefficients were also measured in a flow system where the walls of the flow tube were coated with the SOA proxy and gas-phase species introduced via a moveable inlet. Uptake coefficients were derived from the decay in gas-phase species measured by mass spectrometry. The results of this work will establish a structure-interaction relationship for uptake of gases into SOA that can be implemented into regional and global models.

  10. Gas phase fractionation method using porous ceramic membrane

    DOEpatents

    Peterson, Reid A.; Hill, Jr., Charles G.; Anderson, Marc A.

    1996-01-01

    Flaw-free porous ceramic membranes fabricated from metal sols and coated onto a porous support are advantageously used in gas phase fractionation methods. Mean pore diameters of less than 40 .ANG., preferably 5-20 .ANG. and most preferably about 15 .ANG., are permeable at lower pressures than existing membranes. Condensation of gases in small pores and non-Knudsen membrane transport mechanisms are employed to facilitate and increase membrane permeability and permselectivity.

  11. The Nucleoside Uridine Isolated in the Gas Phase**

    PubMed Central

    Peña, Isabel; Cabezas, Carlos; Alonso, José L.

    2016-01-01

    Herein we present the first experimental observation of the isolated nucleoside uridine, placed in the gas phase by laser ablation and characterized by Fourier transform microwave techniques. Free from the bulk effects of their native environments, anti/C2’-endo-g+ conformation has been revealed as the most stable form of uridine. Intramolecular hydrogen bonds involving uracil and ribose moieties have been found to play an important role in the stabilization of the nucleoside. PMID:25683559

  12. The nucleoside uridine isolated in the gas phase.

    PubMed

    Peña, Isabel; Cabezas, Carlos; Alonso, José L

    2015-03-01

    Herein we present the first experimental observation of the isolated nucleoside uridine, placed in the gas phase by laser ablation and characterized by Fourier transform (FT) microwave techniques. Free from the bulk effects of their native environments, anti/C2'-endo-g+ conformation has been revealed as the most stable form of uridine. Intramolecular hydrogen bonds involving uracil and ribose moieties have been found to play an important role in the stabilization of the nucleoside.

  13. Gas phase chemical detection with an integrated chemical analysis system

    SciTech Connect

    CASALNUOVO,STEPHEN A.; FRYE-MASON,GREGORY CHARLES; KOTTENSTETTE,RICHARD; HELLER,EDWIN J.; MATZKE,CAROLYN M.; LEWIS,PATRICK R.; MANGINELL,RONALD P.; BACA,ALBERT G.; HIETALA,VINCENT M.

    2000-04-12

    Microfabrication technology has been applied to the development of a miniature, multi-channel gas phase chemical laboratory that provides fast response, small size, and enhanced versatility and chemical discrimination. Each analysis channel includes a sample preconcentrator followed by a gas chromatographic separator and a chemically selective surface acoustic wave detector array to achieve high sensitivity and selectivity. The performance of the components, individually and collectively, is described.

  14. Modeling Gas-Phase Chemistry in Cometary Atmospheres

    NASA Astrophysics Data System (ADS)

    Boice, D. C.

    Gas-phase chemistry is central to understand the physics and chemistry of comets. Photochemistry is a major source of ions and electrons that further initiate key gas-phase reactions, leading to the plethora of molecules and atoms seen in cometary atmospheres. The relevant physico-chemical processes are identified within a modeling framework to understand observations and in situ measurements of comets (e.g., Halley, Borrelly, Hyakutake, Hale-Bopp, Tempel 1, Wild 2) and to provide valuable insights into the intrinsic properties of their nuclei. Details of these processes are presented, from the collision-dominated inner coma to the solar wind interaction region. This extensive modeling effort to investigate these important cometary processes is highly relevant to ground-based observations of comets and past, on going, and future spacecraft missions to these primitive objects.Gas-phase chemistry is central to understand the physics and chemistry of comets. Photochemistry is a major source of ions and electrons that further initiate key gas-phase reactions, leading to the plethora of molecules and atoms seen in cometary atmospheres. The relevant physico-chemical processes are identified within a modeling framework to understand observations and in situ measurements of comets (e.g., Halley, Borrelly, Hyakutake, Hale-Bopp, Tempel 1, Wild 2) and to provide valuable insights into the intrinsic properties of their nuclei. Details of these processes are presented, from the collision-dominated inner coma to the solar wind interaction region. This extensive modeling effort to investigate these important cometary processes is highly relevant to ground-based observations of comets and past, on going, and future spacecraft missions to these primitive objects.

  15. A gas-phase amplified quartz crystal microbalance immunosensor based on catalase modified immunoparticles.

    PubMed

    Liu, Wei; Huang, Renliang; Qi, Wei; Wang, Mengfan; Su, Rongxin; He, Zhimin

    2015-02-21

    A novel signal amplification strategy for quartz crystal microbalance (QCM) based on catalytic gas generation was developed to construct an ultrasensitive immunosensor for the detection of proteins (immunoglobulin G, IgG, used as a model). A catalase modified immunoparticle was prepared to form a sandwich-type immunocomplex with the IgG and anti-IgG antibodies that were immobilized on the QCM sensor. The amount of immunoparticles on the sensor surface was thus controlled by the IgG concentration. Then H2O2 was added and catalyzed by catalase for oxygen generation. The generated oxygen replaced some of the liquid on the sensor surface, leading to the change in the shear modulus of the immunocomplex layer and the apparent viscosity and density of the liquid layer. Due to the ultrasensitive response of QCM to these changes, a significant frequency shift related to the IgG concentration was achieved. Different parameters, including the flow cell structure, operation temperature, immunoparticle concentration, and H2O2 concentration were optimized to achieve steady and efficient frequency shifts. Under the optimal conditions, the proposed gas-phase amplified QCM sensor could achieve up to 72 times improvement of detection sensitivity compared to the label-free sensor as a control, in the concentration range of 0.1-3.0 μg mL(-1). The detection limit was also reduced from 236 ng mL(-1) to 51.0 ng mL(-1) at the 3Sblank level.

  16. A gas-phase amplified quartz crystal microbalance immunosensor based on catalase modified immunoparticles.

    PubMed

    Liu, Wei; Huang, Renliang; Qi, Wei; Wang, Mengfan; Su, Rongxin; He, Zhimin

    2015-02-21

    A novel signal amplification strategy for quartz crystal microbalance (QCM) based on catalytic gas generation was developed to construct an ultrasensitive immunosensor for the detection of proteins (immunoglobulin G, IgG, used as a model). A catalase modified immunoparticle was prepared to form a sandwich-type immunocomplex with the IgG and anti-IgG antibodies that were immobilized on the QCM sensor. The amount of immunoparticles on the sensor surface was thus controlled by the IgG concentration. Then H2O2 was added and catalyzed by catalase for oxygen generation. The generated oxygen replaced some of the liquid on the sensor surface, leading to the change in the shear modulus of the immunocomplex layer and the apparent viscosity and density of the liquid layer. Due to the ultrasensitive response of QCM to these changes, a significant frequency shift related to the IgG concentration was achieved. Different parameters, including the flow cell structure, operation temperature, immunoparticle concentration, and H2O2 concentration were optimized to achieve steady and efficient frequency shifts. Under the optimal conditions, the proposed gas-phase amplified QCM sensor could achieve up to 72 times improvement of detection sensitivity compared to the label-free sensor as a control, in the concentration range of 0.1-3.0 μg mL(-1). The detection limit was also reduced from 236 ng mL(-1) to 51.0 ng mL(-1) at the 3Sblank level. PMID:25519742

  17. Transmembrane beta-barrel protein structure prediction

    NASA Astrophysics Data System (ADS)

    Randall, Arlo; Baldi, Pierre

    Transmembrane β-barrel (TMB) proteins are embedded in the outer membranes of mitochondria, Gram-negative bacteria, and chloroplasts. These proteins perform critical functions, including active ion-transport and passive nutrient intake. Therefore, there is a need for accurate prediction of secondary and tertiary structures of TMB proteins. A variety of methods have been developed for predicting the secondary structure and these predictions are very useful for constructing a coarse topology of TMB structure; however, they do not provide enough information to construct a low-resolution tertiary structure for a TMB protein. In addition, while the overall structural architecture is well conserved among TMB proteins, the amino acid sequences are highly divergent. Thus, traditional homology modeling methods cannot be applied to many putative TMB proteins. Here, we describe the TMBpro: a pipeline of methods for predicting TMB secondary structure, β-residue contacts, and finally tertiary structure. The tertiary prediction method relies on the specific construction rules that TMB proteins adhere to and on the predicted β-residue contacts to dramatically reduce the search space for the model building procedure.

  18. Protein NMR structures refined without NOE data.

    PubMed

    Ryu, Hyojung; Kim, Tae-Rae; Ahn, SeonJoo; Ji, Sunyoung; Lee, Jinhyuk

    2014-01-01

    The refinement of low-quality structures is an important challenge in protein structure prediction. Many studies have been conducted on protein structure refinement; the refinement of structures derived from NMR spectroscopy has been especially intensively studied. In this study, we generated flat-bottom distance potential instead of NOE data because NOE data have ambiguity and uncertainty. The potential was derived from distance information from given structures and prevented structural dislocation during the refinement process. A simulated annealing protocol was used to minimize the potential energy of the structure. The protocol was tested on 134 NMR structures in the Protein Data Bank (PDB) that also have X-ray structures. Among them, 50 structures were used as a training set to find the optimal "width" parameter in the flat-bottom distance potential functions. In the validation set (the other 84 structures), most of the 12 quality assessment scores of the refined structures were significantly improved (total score increased from 1.215 to 2.044). Moreover, the secondary structure similarity of the refined structure was improved over that of the original structure. Finally, we demonstrate that the combination of two energy potentials, statistical torsion angle potential (STAP) and the flat-bottom distance potential, can drive the refinement of NMR structures.

  19. Encapsulating Cytochrome c in Silica Aerogel Nanoarchitectures without Metal Nanoparticles while Retaining Gas-phase Bioactivity

    PubMed Central

    Harper-Leatherman, Amanda S.; Pacer, Elizabeth R.; Kosciuszek, Nina D.

    2016-01-01

    Applications such as sensors, batteries, and fuel cells have been improved through the use of highly porous aerogels when functional compounds are encapsulated within the aerogels. However, few reports on encapsulating proteins within sol–gels that are processed to form aerogels exist. A procedure for encapsulating cytochrome c (cyt. c) in silica (SiO2) sol-gels that are supercritically processed to form bioaerogels with gas-phase activity for nitric oxide (NO) is presented. Cyt. c is added to a mixed silica sol under controlled protein concentration and buffer strength conditions. The sol mixture is then gelled and the liquid filling the gel pores is replaced through a series of solvent exchanges with liquid carbon dioxide. The carbon dioxide is brought to its critical point and vented off to form dry aerogels with cyt. c encapsulated inside. These bioaerogels are characterized with UV-visible spectroscopy and circular dichroism spectroscopy and can be used to detect the presence of gas-phase nitric oxide. The success of this procedure depends on regulating the cyt. c concentration and the buffer concentration and does not require other components such as metal nanoparticles. It may be possible to encapsulate other proteins using a similar approach making this procedure important for potential future bioanalytical device development. PMID:26967257

  20. Encapsulating Cytochrome c in Silica Aerogel Nanoarchitectures without Metal Nanoparticles while Retaining Gas-phase Bioactivity.

    PubMed

    Harper-Leatherman, Amanda S; Pacer, Elizabeth R; Kosciuszek, Nina D

    2016-01-01

    Applications such as sensors, batteries, and fuel cells have been improved through the use of highly porous aerogels when functional compounds are encapsulated within the aerogels. However, few reports on encapsulating proteins within sol-gels that are processed to form aerogels exist. A procedure for encapsulating cytochrome c (cyt. c) in silica (SiO2) sol-gels that are supercritically processed to form bioaerogels with gas-phase activity for nitric oxide (NO) is presented. Cyt. c is added to a mixed silica sol under controlled protein concentration and buffer strength conditions. The sol mixture is then gelled and the liquid filling the gel pores is replaced through a series of solvent exchanges with liquid carbon dioxide. The carbon dioxide is brought to its critical point and vented off to form dry aerogels with cyt. c encapsulated inside. These bioaerogels are characterized with UV-visible spectroscopy and circular dichroism spectroscopy and can be used to detect the presence of gas-phase nitric oxide. The success of this procedure depends on regulating the cyt. c concentration and the buffer concentration and does not require other components such as metal nanoparticles. It may be possible to encapsulate other proteins using a similar approach making this procedure important for potential future bioanalytical device development. PMID:26967257

  1. Embracing proteins: structural themes in aptamer-protein complexes.

    PubMed

    Gelinas, Amy D; Davies, Douglas R; Janjic, Nebojsa

    2016-02-01

    Understanding the structural rules that govern specific, high-affinity binding characteristic of aptamer-protein interactions is important in view of the increasing use of aptamers across many applications. From the modest number of 16 aptamer-protein structures currently available, trends are emerging. The flexible phosphodiester backbone allows folding into precise three-dimensional structures using known nucleic acid motifs as scaffolds that orient specific functional groups for target recognition. Still, completely novel motifs essential for structure and function are found in modified aptamers with diversity-enhancing side chains. Aptamers and antibodies, two classes of macromolecules used as affinity reagents with entirely different backbones and composition, recognize protein epitopes of similar size and with comparably high shape complementarity. PMID:26919170

  2. Membrane protein structure determination - the next generation.

    PubMed

    Moraes, Isabel; Evans, Gwyndaf; Sanchez-Weatherby, Juan; Newstead, Simon; Stewart, Patrick D Shaw

    2014-01-01

    The field of Membrane Protein Structural Biology has grown significantly since its first landmark in 1985 with the first three-dimensional atomic resolution structure of a membrane protein. Nearly twenty-six years later, the crystal structure of the beta2 adrenergic receptor in complex with G protein has contributed to another landmark in the field leading to the 2012 Nobel Prize in Chemistry. At present, more than 350 unique membrane protein structures solved by X-ray crystallography (http://blanco.biomol.uci.edu/mpstruc/exp/list, Stephen White Lab at UC Irvine) are available in the Protein Data Bank. The advent of genomics and proteomics initiatives combined with high-throughput technologies, such as automation, miniaturization, integration and third-generation synchrotrons, has enhanced membrane protein structure determination rate. X-ray crystallography is still the only method capable of providing detailed information on how ligands, cofactors, and ions interact with proteins, and is therefore a powerful tool in biochemistry and drug discovery. Yet the growth of membrane protein crystals suitable for X-ray diffraction studies amazingly remains a fine art and a major bottleneck in the field. It is often necessary to apply as many innovative approaches as possible. In this review we draw attention to the latest methods and strategies for the production of suitable crystals for membrane protein structure determination. In addition we also highlight the impact that third-generation synchrotron radiation has made in the field, summarizing the latest strategies used at synchrotron beamlines for screening and data collection from such demanding crystals. This article is part of a Special Issue entitled: Structural and biophysical characterisation of membrane protein-ligand binding.

  3. Fast loop modeling for protein structures

    NASA Astrophysics Data System (ADS)

    Zhang, Jiong; Nguyen, Son; Shang, Yi; Xu, Dong; Kosztin, Ioan

    2015-03-01

    X-ray crystallography is the main method for determining 3D protein structures. In many cases, however, flexible loop regions of proteins cannot be resolved by this approach. This leads to incomplete structures in the protein data bank, preventing further computational study and analysis of these proteins. For instance, all-atom molecular dynamics (MD) simulation studies of structure-function relationship require complete protein structures. To address this shortcoming, we have developed and implemented an efficient computational method for building missing protein loops. The method is database driven and uses deep learning and multi-dimensional scaling algorithms. We have implemented the method as a simple stand-alone program, which can also be used as a plugin in existing molecular modeling software, e.g., VMD. The quality and stability of the generated structures are assessed and tested via energy scoring functions and by equilibrium MD simulations. The proposed method can also be used in template-based protein structure prediction. Work supported by the National Institutes of Health [R01 GM100701]. Computer time was provided by the University of Missouri Bioinformatics Consortium.

  4. Gas-phase microsolvation of ubiquitin: investigation of crown ether complexation sites using ion mobility-mass spectrometry.

    PubMed

    Göth, Melanie; Lermyte, Frederik; Schmitt, Xiao Jakob; Warnke, Stephan; von Helden, Gert; Sobott, Frank; Pagel, Kevin

    2016-10-01

    In this study the gas-phase structure of ubiquitin and its lysine-to-arginine mutants was investigated using ion mobility-mass spectrometry (IM-MS) and electron transfer dissociation-mass spectrometry (ETD-MS). Crown ether molecules were attached to positive charge sites of the proteins and the resulting non-covalent complexes were analysed. Collision induced dissociation (CID) experiments revealed relative energy differences between the wild type and the mutant crown-ether complexes. ETD-MS experiments were performed to identify the crown ether binding sites. Although not all of the binding sites could be revealed, the data confirm that the first crown ether is able to bind to the N-terminus. IM-MS experiments show a more compact structure for specific charge states of wild type ubiquitin when crown ethers are attached. However, data on ubiquitin mutants reveal that only specific lysine residues contribute to the effect of charge microsolvation. A compaction is only observed for one of the investigated mutants, in which the lysine has no proximate interaction partner. On the other hand when the lysine residues are involved in salt bridges, attachment of crown ethers has little effect on the structure. PMID:27494002

  5. Protein Molecular Structures, Protein SubFractions, and Protein Availability Affected by Heat Processing: A Review

    SciTech Connect

    Yu,P.

    2007-01-01

    The utilization and availability of protein depended on the types of protein and their specific susceptibility to enzymatic hydrolysis (inhibitory activities) in the gastrointestine and was highly associated with protein molecular structures. Studying internal protein structure and protein subfraction profiles leaded to an understanding of the components that make up a whole protein. An understanding of the molecular structure of the whole protein was often vital to understanding its digestive behavior and nutritive value in animals. In this review, recently obtained information on protein molecular structural effects of heat processing was reviewed, in relation to protein characteristics affecting digestive behavior and nutrient utilization and availability. The emphasis of this review was on (1) using the newly advanced synchrotron technology (S-FTIR) as a novel approach to reveal protein molecular chemistry affected by heat processing within intact plant tissues; (2) revealing the effects of heat processing on the profile changes of protein subfractions associated with digestive behaviors and kinetics manipulated by heat processing; (3) prediction of the changes of protein availability and supply after heat processing, using the advanced DVE/OEB and NRC-2001 models, and (4) obtaining information on optimal processing conditions of protein as intestinal protein source to achieve target values for potential high net absorbable protein in the small intestine. The information described in this article may give better insight in the mechanisms involved and the intrinsic protein molecular structural changes occurring upon processing.

  6. Proteins with Novel Structure, Function and Dynamics

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew

    2014-01-01

    Recently, a small enzyme that ligates two RNA fragments with the rate of 10(exp 6) above background was evolved in vitro (Seelig and Szostak, Nature 448:828-831, 2007). This enzyme does not resemble any contemporary protein (Chao et al., Nature Chem. Biol. 9:81-83, 2013). It consists of a dynamic, catalytic loop, a small, rigid core containing two zinc ions coordinated by neighboring amino acids, and two highly flexible tails that might be unimportant for protein function. In contrast to other proteins, this enzyme does not contain ordered secondary structure elements, such as alpha-helix or beta-sheet. The loop is kept together by just two interactions of a charged residue and a histidine with a zinc ion, which they coordinate on the opposite side of the loop. Such structure appears to be very fragile. Surprisingly, computer simulations indicate otherwise. As the coordinating, charged residue is mutated to alanine, another, nearby charged residue takes its place, thus keeping the structure nearly intact. If this residue is also substituted by alanine a salt bridge involving two other, charged residues on the opposite sides of the loop keeps the loop in place. These adjustments are facilitated by high flexibility of the protein. Computational predictions have been confirmed experimentally, as both mutants retain full activity and overall structure. These results challenge our notions about what is required for protein activity and about the relationship between protein dynamics, stability and robustness. We hypothesize that small, highly dynamic proteins could be both active and fault tolerant in ways that many other proteins are not, i.e. they can adjust to retain their structure and activity even if subjected to mutations in structurally critical regions. This opens the doors for designing proteins with novel functions, structures and dynamics that have not been yet considered.

  7. Crystallization and Structure Analysis of Membrane Proteins

    NASA Astrophysics Data System (ADS)

    Newman, Richard

    In recent years, there has been great progress in the determination of high-resolution three-dimensional (3D) structures of membrane proteins. The first major breakthrough came with the crystallization (1) and X-ray crystallography (2,3) of the bacterial photosynthetic reaction center (see refs. 4 and 5 for reviews). The structure of another, entirely different membrane protein, the bacterial outer membrane porin from Rhodobacter capsulatus, has now been determined by X-ray crystallography (6). Recent results by electron crystallography of two-dimensional (2D) crystals have been most encouraging. The high-resolution 3D structure of bacteriorhodopsin (7) plant light-harvesting complex (8) and projection maps of several other membrane proteins at similar resolutions (9-11) have been obtained by this technique. Electron crystallography seems particularly appropriate for membrane proteins that are prone to form 2D crystals, and it is hoped that many more structures will be determined in this way.

  8. Contemporary Methodology for Protein Structure Determination.

    ERIC Educational Resources Information Center

    Hunkapiller, Michael W.; And Others

    1984-01-01

    Describes the nature and capabilities of methods used to characterize protein and peptide structure, indicating that they have undergone changes which have improved the speed, reliability, and applicability of the process. Also indicates that high-performance liquid chromatography and gel electrophoresis have made purifying proteins and peptides a…

  9. A 'periodic table' for protein structures.

    PubMed

    Taylor, William R

    2002-04-11

    Current structural genomics programs aim systematically to determine the structures of all proteins coded in both human and other genomes, providing a complete picture of the number and variety of protein structures that exist. In the past, estimates have been made on the basis of the incomplete sample of structures currently known. These estimates have varied greatly (between 1,000 and 10,000; see for example refs 1 and 2), partly because of limited sample size but also owing to the difficulties of distinguishing one structure from another. This distinction is usually topological, based on the fold of the protein; however, in strict topological terms (neglecting to consider intra-chain cross-links), protein chains are open strings and hence are all identical. To avoid this trivial result, topologies are determined by considering secondary links in the form of intra-chain hydrogen bonds (secondary structure) and tertiary links formed by the packing of secondary structures. However, small additions to or loss of structure can make large changes to these perceived topologies and such subjective solutions are neither robust nor amenable to automation. Here I formalize both secondary and tertiary links to allow the rigorous and automatic definition of protein topology.

  10. Structural Characteristics of Novel Protein Folds

    PubMed Central

    Fernandez-Fuentes, Narcis; Dybas, Joseph M.; Fiser, Andras

    2010-01-01

    Folds are the basic building blocks of protein structures. Understanding the emergence of novel protein folds is an important step towards understanding the rules governing the evolution of protein structure and function and for developing tools for protein structure modeling and design. We explored the frequency of occurrences of an exhaustively classified library of supersecondary structural elements (Smotifs), in protein structures, in order to identify features that would define a fold as novel compared to previously known structures. We found that a surprisingly small set of Smotifs is sufficient to describe all known folds. Furthermore, novel folds do not require novel Smotifs, but rather are a new combination of existing ones. Novel folds can be typified by the inclusion of a relatively higher number of rarely occurring Smotifs in their structures and, to a lesser extent, by a novel topological combination of commonly occurring Smotifs. When investigating the structural features of Smotifs, we found that the top 10% of most frequent ones have a higher fraction of internal contacts, while some of the most rare motifs are larger, and contain a longer loop region. PMID:20421995

  11. Information-driven structural modelling of protein-protein interactions.

    PubMed

    Rodrigues, João P G L M; Karaca, Ezgi; Bonvin, Alexandre M J J

    2015-01-01

    Protein-protein docking aims at predicting the three-dimensional structure of a protein complex starting from the free forms of the individual partners. As assessed in the CAPRI community-wide experiment, the most successful docking algorithms combine pure laws of physics with information derived from various experimental or bioinformatics sources. Of these so-called "information-driven" approaches, HADDOCK stands out as one of the most successful representatives. In this chapter, we briefly summarize which experimental information can be used to drive the docking prediction in HADDOCK, and then focus on the docking protocol itself. We discuss and illustrate with a tutorial example a "classical" protein-protein docking prediction, as well as more recent developments for modelling multi-body systems and large conformational changes. PMID:25330973

  12. MOLECULAR SPECTROSCPY AND REACTIONS OF ACTINIDES IN THE GAS PHASE AND CRYOGENIC MATRICES

    SciTech Connect

    Heaven, Michael C.; Gibson, John K.; Marcalo, Joaquim

    2009-02-01

    temperature or below. For many spectroscopic measurements, low temperatures have been achieved by co-condensing the actinide vapor in rare gas or inert molecule host matrices. Spectra recorded in matrices are usually considered to be minimally perturbed. Trapping the products from gas-phase reactions that occur when trace quantities of reactants are added to the inert host gas has resulted in the discovery of many new actinide species. Selected aspects of the matrix isolation data were discussed in chapter 17. In the present chapter we review the spectroscopic matrix data in terms of its relationship to gas-phase measurements, and update the description of the new reaction products found in matrices to reflect the developments that have occurred during the past two years. Spectra recorded in matrix environments are usually considered to be minimally perturbed, and this expectation is borne out for many closed shell actinide molecules. However, there is growing evidence that significant perturbations can occur for open shell molecules, resulting in geometric distortions and/or electronic state reordering. Studies of actinide reactions in the gas phase provide an opportunity to probe the relationship between electronic structure and reactivity. Much of this work has focused on the reactions of ionic species, as these may be selected and controlled using various forms of mass spectrometry. As an example of the type of insight derived from reaction studies, it has been established that the reaction barriers for An+ ions are determined by the promotion energies required to achieve the 5fn6d7s configuration. Gas-phase reaction studies also provide fundamental thermodynamic properties such as bond dissociation and ionization energies. In recent years, an increased number of gas-phase ion chemistry studies of bare (atomic) and ligated (molecular) actinide ions have appeared, in which relevant contributions to fundamental actinide chemistry have been made. These studies were initiated

  13. Metamorphic proteins mediate evolutionary transitions of structure.

    PubMed

    Yadid, Itamar; Kirshenbaum, Noam; Sharon, Michal; Dym, Orly; Tawfik, Dan S

    2010-04-20

    The primary sequence of proteins usually dictates a single tertiary and quaternary structure. However, certain proteins undergo reversible backbone rearrangements. Such metamorphic proteins provide a means of facilitating the evolution of new folds and architectures. However, because natural folds emerged at the early stages of evolution, the potential role of metamorphic intermediates in mediating evolutionary transitions of structure remains largely unexplored. We evolved a set of new proteins based on approximately 100 amino acid fragments derived from tachylectin-2--a monomeric, 236 amino acids, five-bladed beta-propeller. Their structures reveal a unique pentameric assembly and novel beta-propeller structures. Although identical in sequence, the oligomeric subunits adopt two, or even three, different structures that together enable the pentameric assembly of two propellers connected via a small linker. Most of the subunits adopt a wild-type-like structure within individual five-bladed propellers. However, the bridging subunits exhibit domain swaps and asymmetric strand exchanges that allow them to complete the two propellers and connect them. Thus, the modular and metamorphic nature of these subunits enabled dramatic changes in tertiary and quaternary structure, while maintaining the lectin function. These oligomers therefore comprise putative intermediates via which beta-propellers can evolve from smaller elements. Our data also suggest that the ability of one sequence to equilibrate between different structures can be evolutionary optimized, thus facilitating the emergence of new structures.

  14. Interaction Energy Based Protein Structure Networks

    PubMed Central

    Vijayabaskar, M.S.; Vishveshwara, Saraswathi

    2010-01-01

    The three-dimensional structure of a protein is formed and maintained by the noncovalent interactions among the amino-acid residues of the polypeptide chain. These interactions can be represented collectively in the form of a network. So far, such networks have been investigated by considering the connections based on distances between the amino-acid residues. Here we present a method of constructing the structure network based on interaction energies among the amino-acid residues in the protein. We have investigated the properties of such protein energy-based networks (PENs) and have shown correlations to protein structural features such as the clusters of residues involved in stability, formation of secondary and super-secondary structural units. Further we demonstrate that the analysis of PENs in terms of parameters such as hubs and shortest paths can provide a variety of biologically important information, such as the residues crucial for stabilizing the folded units and the paths of communication between distal residues in the protein. Finally, the energy regimes for different levels of stabilization in the protein structure have clearly emerged from the PEN analysis. PMID:21112295

  15. Gas-phase chemistry of ruthenium and rhodium carbonyl complexes.

    PubMed

    Cao, Shiwei; Wang, Yang; Qin, Zhi; Fan, Fangli; Haba, Hiromitsu; Komori, Yukiko; Wu, Xiaolei; Tan, Cunmin; Zhang, Xin

    2016-01-01

    Short-lived ruthenium and rhodium isotopes were produced from a (252)Cf spontaneous fission (SF) source. Their volatile carbonyl complexes were formed in gas-phase reactions in situ with the carbon-monoxide containing gas. A gas-jet system was employed to transport the volatile carbonyls from the recoil chamber to the chemical separation apparatus. The gas-phase chemical behaviors of these carbonyl complexes were studied using an online low temperature isothermal chromatography (IC) technique. Long IC columns made up of FEP Teflon were used to obtain the chemical information of the high-volatile Ru and Rh carbonyls. By excluding the influence of precursor effects, short-lived isotopes of (109-110)Ru and (111-112)Rh were used to represent the chemical behaviours of Ru and Rh carbonyls. Relative chemical yields of about 75% and 20% were measured for Ru(CO)5 and Rh(CO)4, respectively, relative to the yields of KCl aerosols transported in Ar gas. The adsorption enthalpies of ruthenium and rhodium carbonyl complexes on a Teflon surface were determined to be around ΔHads = -33(+1)(-2) kJ mol(-1) and -36(+2)(-1) kJ mol(-1), respectively, by fitting the breakthrough curves of the corresponding carbonyl complexes with a Monte Carlo simulation program. Different from Mo and Tc carbonyls, a small amount of oxygen gas was found to be not effective for the chemical yields of ruthenium and rhodium carbonyl complexes. The general chemical behaviors of short-lived carbonyl complexes of group VI-IX elements were discussed, which can be used in the future study on the gas-phase chemistry of superheavy elements - Bh, Hs, and Mt carbonyls. PMID:26573993

  16. Fluorescence Spectroscopy of Gas-phase Polycyclic Aromatic Hydrocarbons

    NASA Technical Reports Server (NTRS)

    Thomas, J. D.; Witt, A. N.

    2006-01-01

    The purpose of this investigation was to produce fluorescence spectra of polycyclic aromatic hydrocarbon (PAH) molecules in the gas-phase for comparison with blue luminescence (BL) emission observed in astrophysical sources Vijh et al. (2004, 2005a,b). The BL occurs roughly from 350 to 450 nm, with a sharp peak near 380 nm. PAHs with three to four rings, e.g. anthracene and pyrene, were found to produce luminescence in the appropriate spectral region, based on existing studies. Relatively few studies of the gas-phase fluorescence of PAHs exist; those that do exist have dealt primarily with the same samples commonly available for purchase such as pyrene and anthracene. In an attempt to understand the chemistry of the nebular environment we also obtained several nitrogen substituted PAHs from our colleagues at NASA Ames. In order to simulate the astrophysical environment we also took spectra by heating the PAHs in a flame. The flame environment counteracts the formation of eximers and permits the spectroscopy of free-flying neutral molecules. Experiments with coal tar demonstrate that fluorescence spectroscopy reveals primarily the presence of the smallest molecules, which are most abundant and which possess the highest fluorescence efficiencies. One gas-phase PAH that seems to fit the BL spectrum most closely is phenanthridine. In view of the results from the spectroscopy of coal tar, a compound containing a mixture of PAHs ranging from small to very large PAH molecules, we can not preclude the presence of larger PAHs in interstellar sources exhibiting BL.

  17. Multiple gas-phase conformations of proline-containing peptides: is it always cis/trans isomerization?

    PubMed

    Lietz, Christopher B; Chen, Zhengwei; Yun Son, Chang; Pang, Xueqin; Cui, Qiang; Li, Lingjun

    2016-08-01

    Ion mobility-mass spectrometry (IM-MS) is often employed to look at the secondary, tertiary, and quaternary structures of naked peptides and proteins in the gas-phase. Recently, it has offered a unique glimpse into proline-containing peptides and their cis/trans Xxx-Pro isomers. An experimental "signature" has been identified wherein a proline-containing peptide has its Pro residues substituted with another amino acid and the presence or absence of conformations in the IM-MS spectra is observed. Despite the high probability that one could attribute these conformations to cis/trans isomers, it is also possible that cis/trans isomers are not the cause of the additional conformations in proline-containing peptides. However, the experimental evidence of such a system has not been demonstrated or reported. Herein, we present the IM-MS analysis of Neuropeptide Y's wild-type (WT) signal sequence and Leu7Pro (L7P) mutant. Although comparison of arrival times and collision cross-sections of [M + 4H](4+) ions yields the cis/trans "signature", molecular dynamics indicates that a cis-Pro7 is not very stable and that trans-Pro7 conformations of the same cross-section arise with equal frequency. We believe that this work further underscores the importance of theoretical calculations in IM-MS structural assignments. PMID:27434776

  18. Protein folding: When ribosomes pick the structure

    NASA Astrophysics Data System (ADS)

    Sivertsson, Elin M.; Itzhaki, Laura S.

    2014-05-01

    Anfinsen's principle tells us that the folded structure of a protein is determined solely by its sequence. Now, it has been shown that the rate at which a polypeptide chain is synthesized in the cell can affect which of two alternative folded structures it adopts.

  19. Versatile hemidesmosomal linker proteins: structure and function.

    PubMed

    Chaudhari, Pratik R; Vaidya, Milind M

    2015-04-01

    Hemidesmosomes are anchoring junctions which connect basal epidermal cells to the extracellular matrix. In complex epithelia like skin, hemidesmosomes are composed of transmembrane proteins like α6β4 integrin, BP180, CD151 and cytoplasmic proteins like BPAG1e and plectin. BPAG1e and plectin are plakin family cytolinker proteins which anchor intermediate filament proteins i.e. keratins to the hemidesmosomal transmembrane proteins. Mutations in BPAG1e and plectin lead to severe skin blistering disorders. Recent reports indicate that these hemidesmosomal linker proteins play a role in various cellular processes like cell motility and cytoskeleton dynamics apart from their known anchoring function. In this review, we will discuss their role in structural and signaling functions.

  20. Gas-phase peptide fragmentation: how understanding the fundamentals provides a springboard to developing new chemistry and novel proteomic tools.

    PubMed

    Barlow, Christopher K; O'Hair, Richard A J

    2008-10-01

    This tutorial provides an overview of the evolution of some of the key concepts in the gas-phase fragmentation of different classes of peptide ions under various conditions [e.g. collision-induced dissociation (CID) and electron transfer dissociation (ETD)], and then demonstrates how these concepts can be used to develop new methods. For example, an understanding of the role of the mobile proton and neighboring group interactions in the fragmentation reactions of protonated peptides has led to the design of the 'SELECT' method. For ETD, a model based on the Landau-Zener theory reveals the role of both thermodynamic and geometric effects in the electron transfer from polyatomic reagent anions to multiply protonated peptides, and this predictive model has facilitated the design of a new strategy to form ETD reagent anions from precursors generated via ESI. Finally, two promising, emerging areas of gas-phase ion chemistry of peptides are also described: (1) the design of new gas-phase radical chemistry to probe peptide structure, and (2) selective cleavage of disulfide bonds of peptides in the gas phase via various physicochemical approaches.

  1. Gas-phase chemiluminescent reactions of ozone with monoterpenes

    NASA Astrophysics Data System (ADS)

    Arora, P. K.; Chatha, J. P. S.; Vohra, K. G.

    1983-08-01

    Chemiluminescent reactions of ozone with monoterpenes such as linallol, geraniol, d-limonene and α-pinene have been studied in the gas phase at low pressures. Methylglyoxal phosphorescence has been observed in the first two reactions. Emissions from HCHO( 1A 2) and glyoxal ( 3A u) are observed in the reaction of ozone with d-limonene and formation of excited glyoxal is found to be first order in ozone. The reaction of ozone with β-pinene gives rise to emission from a α-dicarbonyl compound and this is found to be first order in ozone. The mechanisms for the formation of excited species are proposed.

  2. Neurotransmitters in the Gas Phase: La-Mb Studies

    NASA Astrophysics Data System (ADS)

    Cabezas, C.; Mata, S.; López, J. C.; Alonso, J. L.

    2011-06-01

    LA-MB-FTMW spectroscopy combines laser ablation with Fourier transform microwave spectroscopy in supersonic jets overcoming the problems of thermal decomposition associated with conventional heating methods. We present here the results on LA-MB-FTMW studies of some neurotransmitters. Six conformers of dopamine, four of adrenaline, five of noradrenaline and three conformers of serotonin have been characterized in the gas phase. The rotational and nuclear quadrupole coupling constants extracted from the analysis of the rotational spectrum are directly compared with those predicted by ab initio methods to achieve the conclusive identification of different conformers and the experimental characterization of the intramolecular forces at play which control conformational preferences.

  3. Gas Phase Chemical Detection with an Integrated Chemical Analysis System

    SciTech Connect

    Baca, Albert G.; Casalnuovo, Stephen A.; Frye-Mason, Gregory C.; Heller, Edwin J.; Hietala, Susan L.; Hietala, Vincent M.; Kottenstette, Richard J.; Lewis, Patrick R.; Manginell, Ronald P.; Matzke, Carloyn M.; Reno, John L.; Sasaki, Darryl Y.; Schubert, W. Kent

    1999-07-08

    Microfabrication technology has been applied to the development of a miniature, multi-channel gas phase chemical laboratory that provides fast response, small size, and enhanced versatility and chemical discrimination. Each analysis channel includes a sample concentrator followed by a gas chromatographic separator and a chemically selective surface acoustic wave detector array to achieve high sensitivity and selectivity. The performance of the components, individually and collectively, is described. The design and performance of novel micromachined acoustic wave devices, with the potential for improved chemical sensitivity, are also described.

  4. Multiscale Aspects of Modeling Gas-Phase Nanoparticle Synthesis

    PubMed Central

    Buesser, B.; Gröhn, A.J.

    2013-01-01

    Aerosol reactors are utilized to manufacture nanoparticles in industrially relevant quantities. The development, understanding and scale-up of aerosol reactors can be facilitated with models and computer simulations. This review aims to provide an overview of recent developments of models and simulations and discuss their interconnection in a multiscale approach. A short introduction of the various aerosol reactor types and gas-phase particle dynamics is presented as a background for the later discussion of the models and simulations. Models are presented with decreasing time and length scales in sections on continuum, mesoscale, molecular dynamics and quantum mechanics models. PMID:23729992

  5. Gas Phase Model of Surface Reactions for N{2} Afterglows

    NASA Astrophysics Data System (ADS)

    Marković, V. Lj.; Petrović, Z. Lj.; Pejović, M. M.

    1996-07-01

    The adequacy of the homogeneous gas phase model as a representation of the surface losses of diffusing active particles in gas phase is studied. As an example the recent data obtained for the surface recombination coefficients are reanalyzed. The data were obtained by the application of the breakdown delay times which consists of the measurements of the breakdown delay times t_d as a function of the afterglow period tau. It was found that for the conditions of our experiment, the diffusion should not be neglected as the final results are significantly different when obtained by approximate gas phase representation and by exact numerical solution to the diffusion equation. While application of the gas phase effective coefficients to represent surface losses gives an error in the value of the recombination coefficient, it reproduces correctly other characteristics such as order of the process which can be obtained from simple fits to the experimental data. Dans cet article, nous étudions la validité du modèle approximatif représentant les pertes superficielles des particules actives qui diffusent de la phase gazeuse comme pertes dans la phase homogène du gaz. Les données actuelles du coefficient de recombination en surface sont utilisées par cette vérification . Les données experimentales sont obtenues en utilisant la technique qui consiste en la mesure du temps de retard du début de la décharge en fonction de la période de relaxation. Nous avons trouvé que, pour nos conditions expérimentales, la diffusion ne peut être négligée. Aussi, les résultats finals sont considérablement différents quand ils sont obtenus en utilisant le modèle approximatif par comparaison aves les résultats obtenus par la solution numérique exacte de l'équation de la diffusion. L'application des coefficients effectifs dans la phase gaseuse pour la présentation des pertes superficielles donne, pour les coefficients de la recombinaison, des valeurs qui diffèrent en

  6. Protein Structure Recognition: From Eigenvector Analysis to Structural Threading Method

    SciTech Connect

    Haibo Cao

    2003-12-12

    In this work, they try to understand the protein folding problem using pair-wise hydrophobic interaction as the dominant interaction for the protein folding process. They found a strong correlation between amino acid sequences and the corresponding native structure of the protein. Some applications of this correlation were discussed in this dissertation include the domain partition and a new structural threading method as well as the performance of this method in the CASP5 competition. In the first part, they give a brief introduction to the protein folding problem. Some essential knowledge and progress from other research groups was discussed. This part includes discussions of interactions among amino acids residues, lattice HP model, and the design ability principle. In the second part, they try to establish the correlation between amino acid sequence and the corresponding native structure of the protein. This correlation was observed in the eigenvector study of protein contact matrix. They believe the correlation is universal, thus it can be used in automatic partition of protein structures into folding domains. In the third part, they discuss a threading method based on the correlation between amino acid sequences and ominant eigenvector of the structure contact-matrix. A mathematically straightforward iteration scheme provides a self-consistent optimum global sequence-structure alignment. The computational efficiency of this method makes it possible to search whole protein structure databases for structural homology without relying on sequence similarity. The sensitivity and specificity of this method is discussed, along with a case of blind test prediction. In the appendix, they list the overall performance of this threading method in CASP5 blind test in comparison with other existing approaches.

  7. How Structure Defines Affinity in Protein-Protein Interactions

    PubMed Central

    Erijman, Ariel; Rosenthal, Eran; Shifman, Julia M.

    2014-01-01

    Protein-protein interactions (PPI) in nature are conveyed by a multitude of binding modes involving various surfaces, secondary structure elements and intermolecular interactions. This diversity results in PPI binding affinities that span more than nine orders of magnitude. Several early studies attempted to correlate PPI binding affinities to various structure-derived features with limited success. The growing number of high-resolution structures, the appearance of more precise methods for measuring binding affinities and the development of new computational algorithms enable more thorough investigations in this direction. Here, we use a large dataset of PPI structures with the documented binding affinities to calculate a number of structure-based features that could potentially define binding energetics. We explore how well each calculated biophysical feature alone correlates with binding affinity and determine the features that could be used to distinguish between high-, medium- and low- affinity PPIs. Furthermore, we test how various combinations of features could be applied to predict binding affinity and observe a slow improvement in correlation as more features are incorporated into the equation. In addition, we observe a considerable improvement in predictions if we exclude from our analysis low-resolution and NMR structures, revealing the importance of capturing exact intermolecular interactions in our calculations. Our analysis should facilitate prediction of new interactions on the genome scale, better characterization of signaling networks and design of novel binding partners for various target proteins. PMID:25329579

  8. TRANSITION STATE FOR THE GAS-PHASE REACTION OF URANIUM HEXAFLUORIDE WITH WATER

    SciTech Connect

    Garrison, S; James Becnel, J

    2008-03-18

    Density Functional Theory and small-core, relativistic pseudopotentials were used to look for symmetric and asymmetric transitions states of the gas-phase hydrolysis reaction of uranium hexafluoride, UF{sub 6}, with water. At the B3LYP/6-31G(d,p)/SDD level, an asymmetric transition state leading to the formation of a uranium hydroxyl fluoride, U(OH)F{sub 5}, and hydrogen fluoride was found with an energy barrier of +77.3 kJ/mol and an enthalpy of reaction of +63.0 kJ/mol (both including zero-point energy corrections). Addition of diffuse functions to all atoms except uranium led to only minor changes in the structure and relative energies of the reacting complex and transition state. However, a significant change in the product complex structure was found, significantly reducing the enthalpy of reaction to +31.9 kJ/mol. Similar structures and values were found for PBE0 and MP2 calculations with this larger basis set, supporting the B3LYP results. No symmetric transition state leading to the direct formation of uranium oxide tetrafluoride, UOF{sub 4}, was found, indicating that the reaction under ambient conditions likely includes several more steps than the mechanisms commonly mentioned. The transition state presented here appears to be the first published transition state for the important gas-phase reaction of UF{sub 6} with water.

  9. Comparing anisotropic displacement parameters in protein structures.

    PubMed

    Merritt, E A

    1999-12-01

    The increasingly widespread use of synchrotron-radiation sources and cryo-preparation of samples in macromolecular crystallography has led to a dramatic increase in the number of macromolecular structures determined at atomic or near-atomic resolution. This permits expansion of the structural model to include anisotropic displacement parameters U(ij) for individual atoms. In order to explore the physical significance of these parameters in protein structures, it is useful to be able to compare quantitatively the electron-density distribution described by the refined U(ij) values associated with corresponding crystallographically independent atoms. This paper presents the derivation of an easily calculated correlation coefficient in real space between two atoms modeled with anisotropic displacement parameters. This measure is used to investigate the degree of similarity between chemically equivalent but crystallographically independent atoms in the set of protein structural models currently available from the Protein Data Bank.

  10. SCOP: a structural classification of proteins database.

    PubMed

    Hubbard, T J; Murzin, A G; Brenner, S E; Chothia, C

    1997-01-01

    The Structural Classification of Proteins (SCOP) database provides a detailed and comprehensive description of the relationships of all known proteins structures. The classification is on hierarchical levels: the first two levels, family and superfamily, describe near and far evolutionary relationships; the third, fold, describes geometrical relationships. The distinction between evolutionary relationships and those that arise from the physics and chemistry of proteins is a feature that is unique to this database, so far. SCOP also provides for each structure links to atomic co-ordinates, images of the structures, interactive viewers, sequence data, data on any conformational changes related to function and literature references. The database is freely accessible on the World Wide Web (WWW) with an entry point at URL http://scop.mrc-lmb.cam.ac.uk/scop/

  11. Structure and Non-Structure of Centrosomal Proteins

    PubMed Central

    Bertero, Michela G.; Boutin, Maïlys; Guarín, Nayibe; Méndez-Giraldez, Raúl; Nuñez, Alfonso; Pedrero, Juan G.; Redondo, Pilar; Sanz, María; Speroni, Silvia; Teichert, Florian; Bruix, Marta; Carazo, José M.; Gonzalez, Cayetano; Reina, José; Valpuesta, José M.; Vernos, Isabelle; Zabala, Juan C.; Montoya, Guillermo; Coll, Miquel; Bastolla, Ugo; Serrano, Luis

    2013-01-01

    Here we perform a large-scale study of the structural properties and the expression of proteins that constitute the human Centrosome. Centrosomal proteins tend to be larger than generic human proteins (control set), since their genes contain in average more exons (20.3 versus 14.6). They are rich in predicted disordered regions, which cover 57% of their length, compared to 39% in the general human proteome. They also contain several regions that are dually predicted to be disordered and coiled-coil at the same time: 55 proteins (15%) contain disordered and coiled-coil fragments that cover more than 20% of their length. Helices prevail over strands in regions homologous to known structures (47% predicted helical residues against 17% predicted as strands), and even more in the whole centrosomal proteome (52% against 7%), while for control human proteins 34.5% of the residues are predicted as helical and 12.8% are predicted as strands. This difference is mainly due to residues predicted as disordered and helical (30% in centrosomal and 9.4% in control proteins), which may correspond to alpha-helix forming molecular recognition features (α-MoRFs). We performed expression assays for 120 full-length centrosomal proteins and 72 domain constructs that we have predicted to be globular. These full-length proteins are often insoluble: Only 39 out of 120 expressed proteins (32%) and 19 out of 72 domains (26%) were soluble. We built or retrieved structural models for 277 out of 361 human proteins whose centrosomal localization has been experimentally verified. We could not find any suitable structural template with more than 20% sequence identity for 84 centrosomal proteins (23%), for which around 74% of the residues are predicted to be disordered or coiled-coils. The three-dimensional models that we built are available at http://ub.cbm.uam.es/centrosome/models/index.php. PMID:23671615

  12. 2003 NIH protein structure intiative workshop in protein production and crystallization for structural and functional genomics.

    SciTech Connect

    Adams, M.; Joachimiak, A.; Kim, R.; Montelione, G. T.; Norvell, J.; Biosciences Division; University of Georgia; LBNL; Rutgers Univ.; Robert Wood Johnson Medical School

    2004-03-01

    The United States National Institutes of Health (NIH) Protein Structure Initiative (PSI) is a joint government, university, and industry effort, organized and supported by the National Institute of General Medical Sciences (NIGMS), and aimed at reducing the costs in increasing the speed of protein structure determination. Its long-range goal is to make the three-dimensional atomic-level structures of most proteins in nature easily obtainable from knowledge of their corresponding DNA sequences (http://www.nigms.gov/psi). It is the primary U.S. component of a broad international effort in structural genomics, involving at least 20 projects throughout the world. The PSI is now in its fourth year. Nine PSI pilot research centers have been funded to explore the feasibility and impact of genomic scale protein structure analysis. To date, over 500 3D protein structures, providing the first structural representatives for hundreds of protein domain families, have been completed and deposited by the NIH centers into the public Protein Data Bank. In addition, new technologies for protein sample production, data organization, and structure analysis by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy have been developed. These technologies increase the efficiency of protein structure determination both for structural genomics and for the broader structural biology community. Although progress has been substantial, PSI pilot research centers have identified a number of important bottlenecks that need to be solved to meet the goals of the program. For example, it is now accepted that a major challenge to high-throughput protein structure determination is the fact that for some 70% of targeted proteins, it is difficult to produce protein samples and crystals suitable for structural analysis. In an effort to facilitate an effective exchange of developments and advancements between pilot centers, the NIGMS organized a workshop on gene cloning, protein

  13. Gas Phase Chromatography of some Group 4, 5, and 6 Halides

    SciTech Connect

    Sylwester, Eric Robert

    1998-10-01

    Gas phase chromatography using The Heavy Element Volatility Instrument (HEVI) and the On Line Gas Apparatus (OLGA III) was used to determine volatilities of ZrBr{sub 4}, HfBr{sub 4}, RfBr{sub 4}, NbBr{sub 5}, TaOBr{sub 3}, HaCl{sub 5}, WBr{sub 6}, FrBr, and BiBr{sub 3}. Short-lived isotopes of Zr, Hf, Rf, Nb, Ta, Ha, W, and Bi were produced via compound nucleus reactions at the 88-Inch Cyclotron at Lawrence Berkeley National Laboratory and transported to the experimental apparatus using a He gas transport system. The isotopes were halogenated, separated from the other reaction products, and their volatilities determined by isothermal gas phase chromatography. Adsorption Enthalpy ({Delta}H{sub a}) values for these compounds were calculated using a Monte Carlo simulation program modeling the gas phase chromatography column. All bromides showed lower volatility than molecules of similar molecular structures formed as chlorides, but followed similar trends by central element. Tantalum was observed to form the oxybromide, analogous to the formation of the oxychloride under the same conditions. For the group 4 elements, the following order in volatility and {Delta}H{sub a} was observed: RfBr{sub 4} > ZrBr{sub 4} > HfBr{sub 4}. The {Delta}H{sub a} values determined for the group 4, 5, and 6 halides are in general agreement with other experimental data and theoretical predictions. Preliminary experiments were performed on Me-bromides. A new measurement of the half-life of {sup 261}Rf was performed. {sup 261}Rf was produced via the {sup 248}Cm({sup 18}O, 5n) reaction and observed with a half-life of 74{sub -6}{sup +7} seconds, in excellent agreement with the previous measurement of 78{sub -6}{sup +11} seconds. We recommend a new half-life of 75{+-}7 seconds for {sup 261}Rf based on these two measurements. Preliminary studies in transforming HEVI from an isothermal (constant temperature) gas phase chromatography instrument to a thermochromatographic (variable temperature

  14. Radical Formation in the Gas-Phase Ozonolysis of Deprotonated Cysteine.

    PubMed

    Khairallah, George N; Maccarone, Alan T; Pham, Huong T; Benton, Timothy M; Ly, Tony; da Silva, Gabriel; Blanksby, Stephen J; O'Hair, Richard A J

    2015-10-26

    Although the deleterious effects of ozone on the human respiratory system are well-known, many of the precise chemical mechanisms that both cause damage and afford protection in the pulmonary epithelial lining fluid are poorly understood. As a key first step to elucidating the intrinsic reactivity of ozone with proteins, its reactions with deprotonated cysteine [Cys-H](-) are examined in the gas phase. Reaction proceeds at near the collision limit to give a rich set of products including 1) sequential oxygen atom abstraction reactions to yield cysteine sulfenate, sulfinate and sulfonate anions, and significantly 2) sulfenate radical anions formed by ejection of a hydroperoxy radical. The free-radical pathway occurs only when both thiol and carboxylate moieties are available, implicating electron-transfer as a key step in this reaction. This novel and facile reaction is also observed in small cys-containing peptides indicating a possible role for this chemistry in protein ozonolysis. PMID:26480331

  15. DSMC Convergence for Microscale Gas-Phase Heat Conduction

    NASA Astrophysics Data System (ADS)

    Rader, D. J.; Gallis, M. A.; Torczynski, J. R.

    2004-11-01

    The convergence of Bird's Direct Simulation Monte Carlo (DSMC) method is investigated for gas-phase heat conduction at typical microscale conditions. A hard-sphere gas is confined between two fully accommodating walls of unequal temperature. Simulations are performed for small system and local Knudsen numbers, so continuum flow exists outside the Knudsen layers. The ratio of the DSMC thermal conductivity to the Chapman-Enskog value in the central region is determined for over 200 combinations of time step, cell size, and number of computational molecules per cell. In the limit of vanishing error, this ratio approaches 1.000 to within the correlation uncertainty. In the limit of infinite computational molecules per cell, the difference from unity depends quadratically on time step and cell size as these quantities become small. The coefficients of these quadratic terms are in good agreement with Green-Kubo values found by Hadjiconstantinou, Garcia, and co-workers. These results demonstrate that DSMC can accurately simulate microscale gas-phase heat conduction. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  16. High resolution dissociative electron attachment to gas phase adenine

    SciTech Connect

    Huber, D.; Beikircher, M.; Denifl, S.; Zappa, F.; Matejcik, S.; Bacher, A.; Grill, V.; Maerk, T. D.; Scheier, P.

    2006-08-28

    The dissociative electron attachment to the gas phase nucleobase adenine is studied using two different experiments. A double focusing sector field mass spectrometer is utilized for measurements requiring high mass resolution, high sensitivity, and relative ion yields for all the fragment anions and a hemispherical electron monochromator instrument for high electron energy resolution. The negative ion mass spectra are discussed at two different electron energies of 2 and 6 eV. In contrast to previous gas phase studies a number of new negative ions are discovered in the mass spectra. The ion efficiency curves for the negative ions of adenine are measured for the electron energy range from about 0 to 15 eV with an electron energy resolution of about 100 meV. The total anion yield derived via the summation of all measured fragment anions is compared with the total cross section for negative ion formation measured recently without mass spectrometry. For adenine the shape of the two cross section curves agrees well, taking into account the different electron energy resolutions; however, for thymine some peculiar differences are observed.

  17. Gas phase oxidation downstream of a catalytic combustor

    NASA Technical Reports Server (NTRS)

    Tien, J. S.; Anderson, D. N.

    1979-01-01

    Effect of the length available for gas-phase reactions downstream of the catalytic reactor on the emission of CO and unburned hydrocarbons was investigated. A premixed, prevaporized propane/air feed to a 12/cm/diameter catalytic/reactor test section was used. The catalytic reactor was made of four 2.5 cm long monolithic catalyst elements. Four water cooled gas sampling probes were located at positions between 0 and 22 cm downstream of the catalytic reactor. Measurements of unburned hydrocarbon, CO, and CO2 were made. Tests were performed with an inlet air temperature of 800 K, a reference velocity of 10 m/s, pressures of 3 and 600,000 Pa, and fuel air equivalence ratios of 0.14 to 0.24. For very lean mixtures, hydrocarbon emissions were high and CO continued to be formed downstream of the catalytic reactor. At the highest equivalence ratios tested, hydrocarbon levels were much lower and CO was oxidized to CO2 in the gas phase downstream. To achieve acceptable emissions, a downstream region several times longer than the catalytic reactor could be required.

  18. Determination of gas phase and surface reactions in plasma polymerization

    NASA Astrophysics Data System (ADS)

    Hegemann, Dirk

    2009-10-01

    Using macroscopic kinetics, the reactions within the gas phase are governed by the reaction parameter power input per gas flow W/F, which corresponds to a specific energy, while reactions by energetic particle bombardment at the growing film surface are rather related to power input W alone. Assuming activation reactions, the mass deposition rate per gas flow can be described by an Arrhenius-like approach: [ RmF=G( -EaW / W F . - F ) ] Mixtures of hydrocarbons (C2H4) and reactive gases (CO2, N2+H2) were examined within low pressure RF plasmas. Thus, functional a-C:H:O or a-C:H:N plasma coatings result. At increasing energy input it is found that the deposited mass shows a deviation from the above equation, commonly related to energetic particle interactions. However, using the same range of W/F with varying power input W, it was found that the observed drop in deposition rate scales solely with energy input W/F for a-C:H:O, i.e. depending on plasma chemistry. a-C:H:N films, on the other hand, show both chemical and physical influences on the film growth. Hence, gas phase reactions such as a change of film-forming species play a major role in plasma polymerization.

  19. Preconceptual design of the gas-phase decontamination demonstration cart

    SciTech Connect

    Munday, E.B.

    1993-12-01

    Removal of uranium deposits from the interior surfaces of gaseous diffusion equipment will be a major portion of the overall multibillion dollar effort to decontaminate and decommission the gaseous diffusion plants. Long-term low-temperature (LTLT) gas-phase decontamination is being developed at the K-25 Site as an in situ decontamination process that is expected to significantly lower the decontamination costs, reduce worker exposure to radioactive materials, and reduce safeguard concerns. This report documents the preconceptual design of the process equipment that is necessary to conduct a full-scale demonstration of the LTLT method in accordance with the process steps listed above. The process equipment and method proposed in this report are not intended to represent a full-scale production campaign design and operation, since the gas evacuation, gas charging, and off-gas handling systems that would be cost effective in a production campaign are not cost effective for a first-time demonstration. However, the design presented here is expected to be applicable to special decontamination projects beyond the demonstration, which could include the Deposit Recovery Program. The equipment will therefore be sized to a 200 ft size 1 converter (plus a substantial conservative design margin), which is the largest item of interest for gas phase decontamination in the Deposit Recovery Program. The decontamination equipment will allow recovery of the UF{sub 6}, which is generated from the reaction of ClF{sub 3} with the uranium deposits, by use of NaF traps.

  20. Gas Phase Reactions of Ions Derived from Anionic Uranyl Formate and Uranyl Acetate Complexes

    NASA Astrophysics Data System (ADS)

    Perez, Evan; Hanley, Cassandra; Koehler, Stephen; Pestok, Jordan; Polonsky, Nevo; Van Stipdonk, Michael

    2016-09-01

    The gas-phase oxidation of doubly protonated peptides containing neutral basic residues to various products, including [M + H + O]+, [M - H]+, and [M - H - NH3]+, is demonstrated here via ion/ion reactions with periodate. It was previously demonstrated that periodate anions are capable of oxidizing disulfide bonds and methionine, tryptophan, and S-alkyl cysteine residues. However, in the absence of these easily oxidized sites, we show here that systems containing neutral basic residues can undergo oxidation. Furthermore, we show that these neutral basic residues primarily undergo different types of oxidation (e.g., hydrogen abstraction) reactions than those observed previously (i.e., oxygen transfer to yield the [M + H + O]+ species) upon gas-phase ion/ion reactions with periodate anions. This chemistry is illustrated with a variety of systems, including a series of model peptides, a cell-penetrating peptide containing a large number of unprotonated basic sites, and ubiquitin, a roughly 8.6 kDa protein.

  1. Structure and function of antifreeze proteins.

    PubMed Central

    Davies, Peter L; Baardsnes, Jason; Kuiper, Michael J; Walker, Virginia K

    2002-01-01

    High-resolution three-dimensional structures are now available for four of seven non-homologous fish and insect antifreeze proteins (AFPs). For each of these structures, the ice-binding site of the AFP has been defined by site-directed mutagenesis, and ice etching has indicated that the ice surface is bound by the AFP. A comparison of these extremely diverse ice-binding proteins shows that they have the following attributes in common. The binding sites are relatively flat and engage a substantial proportion of the protein's surface area in ice binding. They are also somewhat hydrophobic -- more so than that portion of the protein exposed to the solvent. Surface-surface complementarity appears to be the key to tight binding in which the contribution of hydrogen bonding seems to be secondary to van der Waals contacts. PMID:12171656

  2. Structure and Dynamics of Intrinsically Disordered Proteins.

    PubMed

    Fu, Biao; Vendruscolo, Michele

    2015-01-01

    Intrinsically disordered proteins (IDPs) are involved in a wide range of essential biological processes, including in particular signalling and regulation. We are only beginning, however, to develop a detailed knowledge of the structure and dynamics of these proteins. It is becoming increasingly clear that, as IDPs populate highly heterogeneous states, they should be described in terms of conformational ensembles rather than as individual structures, as is instead most often the case for the native states of globular proteins. Within this context, in this chapter we describe the conceptual tools and methodological aspects associated with the description of the structure and dynamics of IDPs in terms of conformational ensembles. A major emphasis is given to methods in which molecular simulations are used in combination with experimental nuclear magnetic resonance (NMR) measurements, as they are emerging as a powerful route to achieve an accurate determination of the conformational properties of IDPs. PMID:26387099

  3. Comparative Protein Structure Modeling Using MODELLER.

    PubMed

    Webb, Benjamin; Sali, Andrej

    2016-01-01

    Comparative protein structure modeling predicts the three-dimensional structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates). The prediction process consists of fold assignment, target-template alignment, model building, and model evaluation. This unit describes how to calculate comparative models using the program MODELLER and how to use the ModBase database of such models, and discusses all four steps of comparative modeling, frequently observed errors, and some applications. Modeling lactate dehydrogenase from Trichomonas vaginalis (TvLDH) is described as an example. The download and installation of the MODELLER software is also described. © 2016 by John Wiley & Sons, Inc. PMID:27322406

  4. Comparative Protein Structure Modeling Using MODELLER.

    PubMed

    Webb, Benjamin; Sali, Andrej

    2016-06-20

    Comparative protein structure modeling predicts the three-dimensional structure of a given protein sequence (target) based primarily on its alignment to one or more proteins of known structure (templates). The prediction process consists of fold assignment, target-template alignment, model building, and model evaluation. This unit describes how to calculate comparative models using the program MODELLER and how to use the ModBase database of such models, and discusses all four steps of comparative modeling, frequently observed errors, and some applications. Modeling lactate dehydrogenase from Trichomonas vaginalis (TvLDH) is described as an example. The download and installation of the MODELLER software is also described. © 2016 by John Wiley & Sons, Inc.

  5. Approximate protein structural alignment in polynomial time.

    PubMed

    Kolodny, Rachel; Linial, Nathan

    2004-08-17

    Alignment of protein structures is a fundamental task in computational molecular biology. Good structural alignments can help detect distant evolutionary relationships that are hard or impossible to discern from protein sequences alone. Here, we study the structural alignment problem as a family of optimization problems and develop an approximate polynomial-time algorithm to solve them. For a commonly used scoring function, the algorithm runs in O(n(10)/epsilon(6)) time, for globular protein of length n, and it detects alignments that score within an additive error of epsilon from all optima. Thus, we prove that this task is computationally feasible, although the method that we introduce is too slow to be a useful everyday tool. We argue that such approximate solutions are, in fact, of greater interest than exact ones because of the noisy nature of experimentally determined protein coordinates. The measurement of similarity between a pair of protein structures used by our algorithm involves the Euclidean distance between the structures (appropriately rigidly transformed). We show that an alternative approach, which relies on internal distance matrices, must incorporate sophisticated geometric ingredients if it is to guarantee optimality and run in polynomial time. We use these observations to visualize the scoring function for several real instances of the problem. Our investigations yield insights on the computational complexity of protein alignment under various scoring functions. These insights can be used in the design of scoring functions for which the optimum can be approximated efficiently and perhaps in the development of efficient algorithms for the multiple structural alignment problem. PMID:15304646

  6. Structural modeling of snow flea antifreeze protein.

    PubMed

    Lin, Feng-Hsu; Graham, Laurie A; Campbell, Robert L; Davies, Peter L

    2007-03-01

    The glycine-rich antifreeze protein recently discovered in snow fleas exhibits strong freezing point depression activity without significantly changing the melting point of its solution (thermal hysteresis). BLAST searches did not detect any protein with significant similarity in current databases. Based on its circular dichroism spectrum, discontinuities in its tripeptide repeat pattern, and intramolecular disulfide bonding, a detailed theoretical model is proposed for the 6.5-kDa isoform. In the model, the 81-residue protein is organized into a bundle of six short polyproline type II helices connected (with one exception) by proline-containing turns. This structure forms two sheets of three parallel helices, oriented antiparallel to each other. The central helices are particularly rich in glycines that facilitate backbone carbonyl-amide hydrogen bonding to four neighboring helices. The modeled structure has similarities to polyglycine II proposed by Crick and Rich in 1955 and is a close match to the polyproline type II antiparallel sheet structure determined by Traub in 1969 for (Pro-Gly-Gly)(n). Whereas the latter two structures are formed by intermolecular interactions, the snow flea antifreeze is stabilized by intramolecular interactions between the helices facilitated by the regularly spaced turns and disulfide bonds. Like several other antifreeze proteins, this modeled protein is amphipathic with a putative hydrophobic ice-binding face. PMID:17158562

  7. Structural modeling of snow flea antifreeze protein.

    PubMed

    Lin, Feng-Hsu; Graham, Laurie A; Campbell, Robert L; Davies, Peter L

    2007-03-01

    The glycine-rich antifreeze protein recently discovered in snow fleas exhibits strong freezing point depression activity without significantly changing the melting point of its solution (thermal hysteresis). BLAST searches did not detect any protein with significant similarity in current databases. Based on its circular dichroism spectrum, discontinuities in its tripeptide repeat pattern, and intramolecular disulfide bonding, a detailed theoretical model is proposed for the 6.5-kDa isoform. In the model, the 81-residue protein is organized into a bundle of six short polyproline type II helices connected (with one exception) by proline-containing turns. This structure forms two sheets of three parallel helices, oriented antiparallel to each other. The central helices are particularly rich in glycines that facilitate backbone carbonyl-amide hydrogen bonding to four neighboring helices. The modeled structure has similarities to polyglycine II proposed by Crick and Rich in 1955 and is a close match to the polyproline type II antiparallel sheet structure determined by Traub in 1969 for (Pro-Gly-Gly)(n). Whereas the latter two structures are formed by intermolecular interactions, the snow flea antifreeze is stabilized by intramolecular interactions between the helices facilitated by the regularly spaced turns and disulfide bonds. Like several other antifreeze proteins, this modeled protein is amphipathic with a putative hydrophobic ice-binding face.

  8. Electronic Relaxation of the Phenylalanine Residue in Gas Phase Peptides: Role of the Neighbouring Amide Groups in the Photophysics

    NASA Astrophysics Data System (ADS)

    Loquais, Y.; Biswal, H. S.; Tardivel, B.; Brenner, V.; Mons, M.; Gloaguen, E.; Jouvet, C.; Broquier, M.; Malis, M.; Ljubic, I.; Doslic, N.

    2012-06-01

    Protein absorption in the near UV is mainly due to the presence of aromatic systems on the side chain of three residues: phenylalanine, tryptophan and tyrosine. It is generally expected that the photophysics of these UV chromophores depends on their immediate environment within the molecule and thus on the conformation of these flexible molecules. This property may in particular be used as an optical diagnostic of the conformational state of the peptide chain. The structure of peptide chains isolated in the gas phase can be characterized by UV and IR laser spectroscopy. These measurements allow us to distinguish the spectral contributions of the different conformers and thus provide us with an elegant way to address the issue of the conformational dependence on the photophysics. For this purpose, the dynamics of relaxation of the ππ* excited state of several peptides containing a phenylalanine residue have been studied using two-colour resonant two-photon ionization (2C-R2PI) in the ns time scale at CEA and ps at CLUPS and laser-induced fluorescence as well. The lifetime of the ππ* excited state is found to strongly depend on the conformation adopted by the molecule and on the excess energy in the excited state, with measured lifetimes ranging from 1 ns to 80 ns. W. Chin; F. Piuzzi; I. Dimicoli and M. Mons, Phys. Chem. Chem. Phys., 8, pp 1033-1048 (2006)

  9. Protein structure and neutral theory of evolution.

    PubMed

    Ptitsyn, O B; Volkenstein, M V

    1986-08-01

    The neutral theory of evolution is extended to the origin of protein molecules. Arguments are presented which suggest that the amino acid sequences of many globular proteins mainly represent "memorized" random sequences while biological evolution reduces to the "editing" these random sequences. Physical requirements for a functional globular protein are formulated and it is shown that many of these requirement do not involve strategical selection of amino acid sequences during biological evolution but are inherent also for typical random sequences. In particular, it is shown that random sequences of polar and amino acid residues can form alpha-helices and beta-strand with lengths and arrangement along the chain similar to those in real globular proteins. These alpha- and beta-regions in random sequences can form three-dimensional folding patterns also similar to those in proteins. The arguments are presented suggesting that even the tight packing of side groups inside protein core do not require very strong biological selection of amino acid sequences either. Thus many structural features of real proteins can exist also in random sequences and the biological selection is needed mainly for the creation of active site of protein and for their stability under physiological conditions.

  10. 1-Phenyl-1,2-dicarba-closo-dodecaborane, 1-Ph-1,2-closo-C(2)B(10)H(11). Synthesis, Characterization, and Structure As Determined in the Gas Phase by Electron Diffraction, in the Crystalline Phase at 199 K by X-ray Diffraction, and by ab Initio Computations.

    PubMed

    Brain, Paul T.; Cowie, Jill; Donohoe, David J.; Hnyk, Drahomír; Rankin, David W. H.; Reed, David; Reid, Bruce D.; Robertson, Heather E.; Welch, Alan J.; Hofmann, Matthias; Schleyer, Paul von Ragué

    1996-03-13

    The compound 1-phenyl-1,2-dicarba-closo-dodecaborane(12), 1-C(6)H(5)-1,2-closo-C(2)B(10)H(11) (1), has been synthesized and characterized by a complete assignment of its (11)B NMR spectrum via (11)B{(1)H}/(11)B{(1)H} (COSY), (1)H{(11)B(selective)} and (1)H{(11)B}/(1)H{(11)B} (COSY) spectroscopy. An electron- and X-ray diffraction investigation of 1, complemented by ab initio calculations, has been undertaken. The gas-phase electron-diffraction (GED) data can be fitted by several models describing conformations which differ in the position of the phenyl ring with respect to the carborane cage. Local symmetries ofC(2)(v)() and D(6)(h)() for the 1,2-C(2)B(10) and C(6) moieties, respectively, were adopted in the GED model in order to simplify the problem. In addition, constraints among the close-lying C-C and B-B bonds were employed. However, even though such simplifications led to satisfactory refinements (R(G) = 0.069-0.071), a unique, definitive solution could not be gained. The (C-C)(mean), (C-B)(mean) and (B-B)(mean) bond lengths,r(a), are ca. 1.44, 1.72, and 1.78 Å, respectively. The C(6) hexagon, with r(a)(C-C) = ca. 1.394 Å, either eclipses the C(1)-C(2) vector (overall C(s)() symmetry) or more or less eclipses the C(1)-B(4) cluster bond (overall C(1) symmetry). In contrast, in the solid at 199 K, the ring lies at a position intermediate between the two GED positions, as determined by X-ray crystallography [C(8)H(16)B(10), monoclinic P2(1)/a: a = 12.047(3) Å, b = 18.627(4) Å, c = 12.332(5) Å, beta = 110.09(4) degrees, Z = 8]. The C-B distances span the range 1.681(6)-1.743(5) Å, and B-B lengths lie between 1.756(6) and 1.795(6) Å. A similar conformation was found for the theoretical (RHF/6-31G level) structure which was fully optimized in C(1) symmetry. The r(e) distances are consistent with the dimensions derived in the experimental studies. IGLO calculations of the (11)B chemical shifts, in addition to SCF single-point energies of the GED structures

  11. 1-Phenyl-1,2-dicarba-closo-dodecaborane, 1-Ph-1,2-closo-C(2)B(10)H(11). Synthesis, Characterization, and Structure As Determined in the Gas Phase by Electron Diffraction, in the Crystalline Phase at 199 K by X-ray Diffraction, and by ab Initio Computations.

    PubMed

    Brain, Paul T.; Cowie, Jill; Donohoe, David J.; Hnyk, Drahomír; Rankin, David W. H.; Reed, David; Reid, Bruce D.; Robertson, Heather E.; Welch, Alan J.; Hofmann, Matthias; Schleyer, Paul von Ragué

    1996-03-13

    The compound 1-phenyl-1,2-dicarba-closo-dodecaborane(12), 1-C(6)H(5)-1,2-closo-C(2)B(10)H(11) (1), has been synthesized and characterized by a complete assignment of its (11)B NMR spectrum via (11)B{(1)H}/(11)B{(1)H} (COSY), (1)H{(11)B(selective)} and (1)H{(11)B}/(1)H{(11)B} (COSY) spectroscopy. An electron- and X-ray diffraction investigation of 1, complemented by ab initio calculations, has been undertaken. The gas-phase electron-diffraction (GED) data can be fitted by several models describing conformations which differ in the position of the phenyl ring with respect to the carborane cage. Local symmetries ofC(2)(v)() and D(6)(h)() for the 1,2-C(2)B(10) and C(6) moieties, respectively, were adopted in the GED model in order to simplify the problem. In addition, constraints among the close-lying C-C and B-B bonds were employed. However, even though such simplifications led to satisfactory refinements (R(G) = 0.069-0.071), a unique, definitive solution could not be gained. The (C-C)(mean), (C-B)(mean) and (B-B)(mean) bond lengths,r(a), are ca. 1.44, 1.72, and 1.78 Å, respectively. The C(6) hexagon, with r(a)(C-C) = ca. 1.394 Å, either eclipses the C(1)-C(2) vector (overall C(s)() symmetry) or more or less eclipses the C(1)-B(4) cluster bond (overall C(1) symmetry). In contrast, in the solid at 199 K, the ring lies at a position intermediate between the two GED positions, as determined by X-ray crystallography [C(8)H(16)B(10), monoclinic P2(1)/a: a = 12.047(3) Å, b = 18.627(4) Å, c = 12.332(5) Å, beta = 110.09(4) degrees, Z = 8]. The C-B distances span the range 1.681(6)-1.743(5) Å, and B-B lengths lie between 1.756(6) and 1.795(6) Å. A similar conformation was found for the theoretical (RHF/6-31G level) structure which was fully optimized in C(1) symmetry. The r(e) distances are consistent with the dimensions derived in the experimental studies. IGLO calculations of the (11)B chemical shifts, in addition to SCF single-point energies of the GED structures

  12. Principles of protein-protein recognition from structure to thermodynamics.

    PubMed

    Janin, J

    1995-01-01

    Specific recognition is illustrated by X-ray structures of protease-inhibitor, antigen-antibody and other high affinity complexes including five electron transfer complexes. We attempt to give a physical definition to affinity and specificity on the basis of these data. In a protein-protein complex, specific recognition results from the assembly of complementary surfaces into well-packed interfaces that cover about 1500 A2 and contain about ten hydrogen bonds. These interfaces are larger than between molecules in protein crystals, and smaller than between subunits in oligomeric proteins. We relate the size and chemical nature of interfaces in complexes to the thermodynamical parameters that characterize affinity: the heat capacity and free enthalpy (Gibbs energy) of dissociation at equilibrium, the activation free enthalpy for the dissociation reaction. The same structural and thermodynamical parameters are inadequate for representing the specificity of recognition. We propose instead to describe specificity with the help of statistical physics, and we illustrate the application of the random energy model to antigen-antibody recognition by analyzing results of computer simulations by docking.

  13. Atomic-level analysis of membrane-protein structure.

    PubMed

    Hendrickson, Wayne A

    2016-06-01

    Membrane proteins are substantially more challenging than natively soluble proteins as subjects for structural analysis. Thus, membrane proteins are greatly underrepresented in structural databases. Recently, focused consortium efforts and advances in methodology for protein production, crystallographic analysis and cryo-EM analysis have accelerated the pace of atomic-level structure determination of membrane proteins.

  14. Trends in structural coverage of the protein universe and the impact of the Protein Structure Initiative.

    PubMed

    Khafizov, Kamil; Madrid-Aliste, Carlos; Almo, Steven C; Fiser, Andras

    2014-03-11

    The exponential growth of protein sequence data provides an ever-expanding body of unannotated and misannotated proteins. The National Institutes of Health-supported Protein Structure Initiative and related worldwide structural genomics efforts facilitate functional annotation of proteins through structural characterization. Recently there have been profound changes in the taxonomic composition of sequence databases, which are effectively redefining the scope and contribution of these large-scale structure-based efforts. The faster-growing bacterial genomic entries have overtaken the eukaryotic entries over the last 5 y, but also have become more redundant. Despite the enormous increase in the number of sequences, the overall structural coverage of proteins--including proteins for which reliable homology models can be generated--on the residue level has increased from 30% to 40% over the last 10 y. Structural genomics efforts contributed ∼50% of this new structural coverage, despite determining only ∼10% of all new structures. Based on current trends, it is expected that ∼55% structural coverage (the level required for significant functional insight) will be achieved within 15 y, whereas without structural genomics efforts, realizing this goal will take approximately twice as long.

  15. Reconstruction of SAXS Profiles from Protein Structures

    PubMed Central

    Putnam, Daniel K.; Lowe, Edward W.

    2013-01-01

    Small angle X-ray scattering (SAXS) is used for low resolution structural characterization of proteins often in combination with other experimental techniques. After briefly reviewing the theory of SAXS we discuss computational methods based on 1) the Debye equation and 2) Spherical Harmonics to compute intensity profiles from a particular macromolecular structure. Further, we review how these formulas are parameterized for solvent density and hydration shell adjustment. Finally we introduce our solution to compute SAXS profiles utilizing GPU acceleration. PMID:24688746

  16. Utilization of Protein Crystal Structures in Industry

    NASA Astrophysics Data System (ADS)

    Ishikawa, Kohki

    In industry, protein crystallography is used in mainly two technologies. One is structure-based drug design, and the other is structure-based enzyme engineering. Some successful cases together with recent advances are presented in this article. The cases include the development of an anti-influenza drug, and the introduction of engineered acid phosphatase to the manufacturing process of nucleotides used as umami seasoning.

  17. Structural origins of diamagnetic anisotropy in proteins.

    PubMed Central

    Worcester, D L

    1978-01-01

    Magnetic anisotropy in proteins and polypeptides can be attributed to the diamagnetic anisotropy of the planar peptide bonds. The alpha helix in particular has large anisotropy due to the axial alignment of the peptide bonds. The regular arrangements of the peptide bonds in beta pleated sheet and collagen structures also produce substantial anisotropy, but less than for alpha helix. The anisotropy permits orientation of small structures of these types in magnetic fields of several kilogauss. PMID:281695

  18. Mapping protein and nucleic acid structure

    NASA Astrophysics Data System (ADS)

    Bednyakov, I. V.; Zrelov, P. V.; Ivanov, V. V.; Polozov, R. V.; Sivozhelezov, V. S.; Stepanenko, V. A.; Chirgadze, Yu. N.

    2013-09-01

    Methods and algorithms to analyze surfaces of globular and fibrillar proteins, DNA, and RNA have been developed. These methods for the construction of maps of fragments of these objects in the original cylindrical projection developed herein essentially broaden the possibilities for studying the distribution of charges and surface topography of biological structures. This approach significantly supplements the qualitative characteristics of methods of visualizing biopolymer structures.

  19. Ultrafast electron diffraction from laser-aligned molecules in the gas phase

    NASA Astrophysics Data System (ADS)

    Yang, Jie

    Ultrafast electron diffraction has emerged since the end of last century, and has become an increasingly important tool for revealing great details of molecular dynamics. In comparison to spectroscopic techniques, ultrafast electron diffraction directly probes time-resolved structure of target molecules, and therefore can potentially provide "molecular movies" of the reactions being studied. These molecular movies are critical for understanding and ultimately controlling the energy conversion pathways and efficiencies of photochemical processes. In this dissertation, I have focused on ultrafast electron diffraction from gas-phase molecules, and have investigated several long-standing challenges that have been preventing researchers from being able to achieve 3-D molecular movies of photochemical reactions. The first challenge is to resolve the full 3-D structure for molecules in the gas phase. The random orientation of molecules in the gas phase smears out the diffraction signal, which results in only 1-D structural information being accessible. The second challenge lies in temporal resolution. In order to resolve coherent nuclear motions on their natural time scale, a temporal resolution of ˜200 femtosecond or better is required. However, due to experimental limitations the shortest temporal resolution that had been achieved was only a few picoseconds in early 2000, by Zewail group from Caltech. The first challenge is tackled by laser-alignment. In the first half of the dissertation, I approach this method both theoretically and experimentally, and demonstrate that by using a short laser pulse to transiently align target molecules in space, 3-D molecular structure can be reconstructed ab-initio from diffraction patterns. The second half of the dissertation presents two experiments, both of which are important steps toward imaging coherent nuclear motions in real time during photochemical reactions. The first experiment simultaneously resolves molecular alignment

  20. Structural mechanisms of nonplanar hemes in proteins

    SciTech Connect

    Shelnutt, J.A.

    1997-05-01

    The objective is to assess the occurrence of nonplanar distortions of hemes and other tetrapyrroles in proteins and to determine the biological function of these distortions. Recently, these distortions were found by us to be conserved among proteins belonging to a functional class. Conservation of the conformation of the heme indicates a possible functional role. Researchers have suggested possible mechanisms by which heme distortions might influence biological properties; however, no heme distortion has yet been shown conclusively to participate in a structural mechanism of hemoprotein function. The specific aims of the proposed work are: (1) to characterize and quantify the distortions of the hemes in all of the more than 300 hemoprotein X-ray crystal structures in terms of displacements along the lowest-frequency normal coordinates, (2) to determine the structural features of the protein component that generate and control these nonplanar distortions by using spectroscopic studies and molecular-mechanics calculations for the native proteins, their mutants and heme-peptide fragments, and model porphyrins, (3) to determine spectroscopic markers for the various types of distortion, and, finally, (4) to discover the functional significance of the nonplanar distortions by correlating function with porphyrin conformation for proteins and model porphyrins.

  1. The lipocalin protein family: structure and function.

    PubMed Central

    Flower, D R

    1996-01-01

    The lipocalin protein family is a large group of small extracellular proteins. The family demonstrates great diversity at the sequence level; however, most lipocalins share three characteristic conserved sequence motifs, the kernel lipocalins, while a group of more divergent family members, the outlier lipocalins, share only one. Belying this sequence dissimilarity, lipocalin crystal structures are highly conserved and comprise a single eight-stranded continuously hydrogen-bonded antiparallel beta-barrel, which encloses an internal ligand-binding site. Together with two other families of ligand-binding proteins, the fatty-acid-binding proteins (FABPs) and the avidins, the lipocalins form part of an overall structural superfamily: the calycins. Members of the lipocalin family are characterized by several common molecular-recognition properties: the ability to bind a range of small hydrophobic molecules, binding to specific cell-surface receptors and the formation of complexes with soluble macromolecules. The varied biological functions of the lipocalins are mediated by one or more of these properties. In the past, the lipocalins have been classified as transport proteins; however, it is now clear that the lipocalins exhibit great functional diversity, with roles in retinol transport, invertebrate cryptic coloration, olfaction and pheromone transport, and prostaglandin synthesis. The lipocalins have also been implicated in the regulation of cell homoeostasis and the modulation of the immune response, and, as carrier proteins, to act in the general clearance of endogenous and exogenous compounds. PMID:8761444

  2. Metal-ligand redox reactions in gas-phase quaternary peptide-metal complexes by electrospray ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Vaisar, T.; Gatlin, C. L.; Turecek, F.

    1997-03-01

    The dipeptides Phe-Leu, Leu-Phe, Leu-Ala, and Ala-Leu form quaternary complexes of the type [Cu(II)(peptide - 2H+M)bpy]+ in the gas phase when electrosprayed in the presence of Cu(II) salts, 2.2'-bipyridyl (bpy), and an alkali hydroxide (MOH). The gas-phase complexes decarboxylate on collisional activation at low ion kinetic energies. The resulting ions undergo unusual eliminations of neutral Na, K, and Rb, which depend on the peptide structure. The ionization energy of the decarboxylated Phe-Leu-Cu-bpy complex was bracketed at 4.2 eV. Other collision-induced dissociations also depend on the alkali metal ion and the peptide structure. Ab initio calculations on a model system are reported and used to discuss the electronic properties of the peptide complexes.

  3. Gas-phase basicities of polyfunctional molecules. Part 4: Carbonyl groups as basic sites.

    PubMed

    Bouchoux, Guy

    2015-01-01

    This article constitutes the fourth part of a general review of the gas-phase protonation thermochemistry of polyfunctional molecules (Part 1: Theory and methods, Mass Spectrom Rev 2007, 26:775-835, Part 2: Saturated basic sites, Mass Spectrom Rev 2012, 31:353-390, Part 3: Amino acids, Mass Spectrom Rev 2012, 31:391-435). This fourth part is devoted to carbonyl containing polyfunctional molecules. After a short reminder of the methods of determination of gas-phase basicity and the underlying physicochemical concepts, specific examples are examined under two major chapters. In the first one, aliphatic and unsaturated (conjugated and cyclic) ketones, diketones, ketoalcohols, and ketoethers are considered. A second chapter describes the protonation energetic of gaseous acids and derivatives including diacids, diesters, diamides, anhydrides, imides, ureas, carbamates, amino acid derivatives, and peptides. Experimental data were re-evaluated according to the presently adopted basicity scale. Structural and energetic information given by G3 and G4 quantum chemistry computations on typical systems are presented.

  4. Gas-Phase Amidation of Carboxylic Acids with Woodward's Reagent K Ions.

    PubMed

    Peng, Zhou; Pilo, Alice L; Luongo, Carl A; McLuckey, Scott A

    2015-10-01

    Gas-phase amidation of carboxylic acids in multiply-charged peptides is demonstrated via ion/ion reactions with Woodward's reagent K (wrk) in both positive and negative mode. Woodward's reagent K, N-ethyl-3-phenylisoxazolium-3'-sulfonate, is a commonly used reagent that activates carboxylates to form amide bonds with amines in solution. Here, we demonstrate that the analogous gas-phase chemistry occurs upon reaction of the wrk ions and doubly protonated (or doubly deprotonated) peptide ions containing the carboxylic acid functionality. The reaction involves the formation of the enol ester intermediate in the electrostatic complex. Upon collisional activation, the ethyl amine on the reagent is transferred to the activated carbonyl carbon on the peptide, resulting in the formation of an ethyl amide (addition of 27 Da to the peptide) with loss of a neutral ketene derivative. Further collision-induced dissociation (CID) of the products and comparison with solution-phase amidation product confirms the structure of the ethyl amide.

  5. Inclusion Complexes of Ionic Liquids and Cyclodextrins: Are They Formed in the Gas Phase?

    NASA Astrophysics Data System (ADS)

    Fernandes, Ana M.; Schröder, Bernd; Barata, Tânia; Freire, Mara G.; Coutinho, João A. P.

    2014-05-01

    The interaction of imidazolium-based ionic liquids with α- and β-cyclodextrins was investigated by electrospray ionization mass spectrometry with variable collision induced dissociation energy and quantum chemical gas-phase calculations. The center-of-mass energy at which 50 % of a precursor ion decomposes (Ecm,1/2) was determined for the isolated [cyclodextrin + cation]+ or [cyclodextrin + anion]- adduct ions of imidazolium-based ionic liquids with different alkyl chain lengths combined with a large set of anions, such as chloride, bromide, bis(trifluoromethylsulfonyl)imide, tetrafluoroborate, hexafluorophosphate, trifluoromethanesulfonate, methanesulfonate, dicyanamide, and hydrogensulfate. Moreover, both symmetric and asymmetric imidazolium cationic cores were evaluated. The relative interaction energies in the adduct ions were interpreted in terms of the influence of cation/anion structures and their inherent properties, such as hydrophobicity and hydrogen bond accepting ability, in the complexation process with the cyclodextrins. The trends observed in the mass spectral data together with quantum-chemical calculations suggest that in the gas phase, cations and anions will preferentially interact with the lower or upper rim of the cyclodextrin, respectively, as opposed to what has been reported in condensed phase where the formation of an inclusion complex between ionic liquid and cyclodextrin is assumed.

  6. Detection of the Elusive Triazane Molecule (N3 H5 ) in the Gas Phase.

    PubMed

    Förstel, Marko; Maksyutenko, Pavlo; Jones, Brant M; Sun, Bing-Jian; Chen, Shih-Hua; Chang, Agnes H-H; Kaiser, Ralf I

    2015-10-26

    We report the detection of triazane (N3 H5 ) in the gas phase. Triazane is a higher order nitrogen hydride of ammonia (NH3 ) and hydrazine (N2 H4 ) of fundamental importance for the understanding of the stability of single-bonded chains of nitrogen atoms and a potential key intermediate in hydrogen-nitrogen chemistry. The experimental results along with electronic-structure calculations reveal that triazane presents a stable molecule with a nitrogen-nitrogen bond length that is a few picometers shorter than that of hydrazine and has a lifetime exceeding 6±2 μs at a sublimation temperature of 170 K. Triazane was synthesized through irradiation of ammonia ice with energetic electrons and was detected in the gas phase upon sublimation of the ice through soft vacuum ultraviolet (VUV) photoionization coupled with a reflectron-time-of-flight mass spectrometer. Isotopic substitution experiments exploiting [D3 ]-ammonia ice confirmed the identification through the detection of its fully deuterated counterpart [D5 ]-triazane (N3 D5 ).

  7. Gas-Phase Amidation of Carboxylic Acids with Woodward's Reagent K Ions

    NASA Astrophysics Data System (ADS)

    Peng, Zhou; Pilo, Alice L.; Luongo, Carl A.; McLuckey, Scott A.

    2015-06-01

    Gas-phase amidation of carboxylic acids in multiply-charged peptides is demonstrated via ion/ion reactions with Woodward's reagent K (wrk) in both positive and negative mode. Woodward's reagent K, N-ethyl-3-phenylisoxazolium-3'-sulfonate, is a commonly used reagent that activates carboxylates to form amide bonds with amines in solution. Here, we demonstrate that the analogous gas-phase chemistry occurs upon reaction of the wrk ions and doubly protonated (or doubly deprotonated) peptide ions containing the carboxylic acid functionality. The reaction involves the formation of the enol ester intermediate in the electrostatic complex. Upon collisional activation, the ethyl amine on the reagent is transferred to the activated carbonyl carbon on the peptide, resulting in the formation of an ethyl amide (addition of 27 Da to the peptide) with loss of a neutral ketene derivative. Further collision-induced dissociation (CID) of the products and comparison with solution-phase amidation product confirms the structure of the ethyl amide.

  8. Nanoparticles-chemistry, new synthetic approaches, gas phase clustering and novel applications

    NASA Astrophysics Data System (ADS)

    Sreekumaran Nair, A.; Subramaniam, Chandramouli; Rosemary, M. J.; Tom, Renjis T.; Rajeev Kumar, V. R.; Jeba Singh, D. M. David; Cyriac, Jobin; Jain, Prashant; Kalesh, K. A.; Bhattacharya, Shreya; Pradeep, T.

    2005-10-01

    In this paper, an overview of the synthesis, chemistry and applications of nanosystems carried out in our laboratory is presented. The discussion is divided into four sections, namely (a) chemistry of nanoparticles, (b) development of new synthetic approaches, (c) gas phase clusters and (d) device structures and applications. In `chemistry of nanoparticles' we describe a novel reaction between nanoparticles of Ag and Au with halocarbons. The reactions lead to the formation of various carbonaceous materials and metal halides. In `development of new synthetic approaches' our one-pot methodologies for the synthesis of core-shell nanosystems of Au, Ag and Cu protected with TiO_2 and ZrO_2 as well as various polymers are discussed. Some results on the interaction of nanoparticles with biomolecules are also detailed in this section. The third section covers the formation of gas phase aggregates/clusters of thiol-protected sub-nanoparticles. Laser desorption of H_2MoO_4, H_2WO_4, MoS_2, and WS_2 giving novel clusters is discussed. The fourth section deals with the development of simple devices and technologies using nanomaterials described above.

  9. Mass spectrometric study of gas-phase ions of acid β-glucosidase (Cerezyme) and iminosugar pharmacological chaperones.

    PubMed

    Rajabi, Khadijeh

    2014-10-01

    The effect on the conformations and stability of gas-phase ions of Cerezyme, a glycoprotein, when bound to three small-molecule chaperones has been studied using intact ESI MS, collision cross section and MS/MS measurements. To distinguish between the peaks from apo and small-molecule complex ions, Cerezyme is deglycosylated (dg-Cer). ESI MS of dg-Cer reveals that glycosylation accounts for 8.5% of the molecular weight. When excess chaperone, either covalent (2FGF) or noncovalent (A and B iminosugars), is added to solutions of dg-Cer, mass spectra show peaks from 1:1 chaperone-enzyme complexes as well as free enzyme. On average, ions of the apoenzyme have 1.6 times higher cross sections when activated in the source region of the mass spectrometer. For a given charge state, ions of complexes of 2FGF and B have about 30% and 8.4% lower cross sections, respectively, compared to the apoenzyme. Thus, binding the chaperones causes the gas-phase protein to adopt more compact conformations. The noncovalent complex ions dissociate by the loss of charged chaperones. In the gas phase, the relative stability of dg-Cer with B is higher than that with the A, whereas in solution A binds enzyme more strongly than B. Nevertheless, the disagreement is explained based on the greater number of contacts between the B and dg-Cer than the A and dg-Cer (13 vs. 8), indicating the importance of noncovalent interactions within the protein-chaperone complex in the absence of solvent. Findings in this work suggest a hypothesis towards predicting a consistent correlation between gas-phase properties to solution binding properties. PMID:25303390

  10. Gas-phase synthesis of magnetic metal/polymer nanocomposites

    NASA Astrophysics Data System (ADS)

    Starsich, Fabian H. L.; Hirt, Ann M.; Stark, Wendelin J.; Grass, Robert N.

    2014-12-01

    Highly magnetic metal Co nanoparticles were produced via reducing flame spray pyrolysis, and directly coated with an epoxy polymer in flight. The polymer content in the samples varied between 14 and 56 wt% of nominal content. A homogenous dispersion of Co nanoparticles in the resulting nanocomposites was visualized by electron microscopy. The size and crystallinity of the metallic fillers was not affected by the polymer, as shown by XRD and magnetic hysteresis measurements. The good control of the polymer content in the product nanocomposite was shown by elemental analysis. Further, the successful polymerization in the gas phase was demonstrated by electron microscopy and size measurements. The presented effective, dry and scalable one-step synthesis method for highly magnetic metal nanoparticle/polymer composites presented here may drastically decrease production costs and increase industrial yields.

  11. Gas-phase synthesis of magnetic metal/polymer nanocomposites.

    PubMed

    Starsich, Fabian H L; Hirt, Ann M; Stark, Wendelin J; Grass, Robert N

    2014-12-19

    Highly magnetic metal Co nanoparticles were produced via reducing flame spray pyrolysis, and directly coated with an epoxy polymer in flight. The polymer content in the samples varied between 14 and 56 wt% of nominal content. A homogenous dispersion of Co nanoparticles in the resulting nanocomposites was visualized by electron microscopy. The size and crystallinity of the metallic fillers was not affected by the polymer, as shown by XRD and magnetic hysteresis measurements. The good control of the polymer content in the product nanocomposite was shown by elemental analysis. Further, the successful polymerization in the gas phase was demonstrated by electron microscopy and size measurements. The presented effective, dry and scalable one-step synthesis method for highly magnetic metal nanoparticle/polymer composites presented here may drastically decrease production costs and increase industrial yields. PMID:25422410

  12. Synthesis and Gas Phase Thermochemistry of Germanium-Containing Compounds

    SciTech Connect

    Nathan Robert Classen

    2002-12-31

    The driving force behind much of the work in this dissertation was to gain further understanding of the unique olefin to carbene isomerization observed in the thermolysis of 1,1-dimethyl-2-methylenesilacyclobutane by finding new examples of it in other silicon and germanium compounds. This lead to the examination of a novel phenylmethylenesilacyclobut-2-ene, which did not undergo olefin to carbene rearrangement. A synthetic route to methylenegermacyclobutanes was developed, but the methylenegermacyclobutane system exhibited kinetic instability, making the study of the system difficult. In any case the germanium system decomposed through a complex mechanism which may not include olefin to carbene isomerization. However, this work lead to the study of the gas phase thermochemistry of a series of dialkylgermylene precursors in order to better understand the mechanism of the thermal decomposition of dialkylgermylenes. The resulting dialkylgermylenes were found to undergo a reversible intramolecular {beta} C-H insertion mechanism.

  13. Conformational Study of Taurine in the Gas Phase

    NASA Astrophysics Data System (ADS)

    Cortijo, Vanessa; Sanz, M. Eugenia; López, Juan C.; Alonso, José L.

    2009-08-01

    The conformational preferences of the amino sulfonic acid taurine (NH2-CH2-CH2-SO3H) have been investigated in the gas phase by laser ablation molecular beam Fourier transform microwave spectroscopy (LA-MB-FTMW) in the 6-14 GHz frequency range. One conformer has been observed, and its rotational, centrifugal distortion, and hyperfine quadrupole coupling constants have been determined from the analysis of its rotational spectrum. Comparison of the experimental constants with those calculated theoretically identifies the detected conformer unambiguously. The observed conformer of taurine is stabilized by an intramolecular hydrogen bond O-H···N between the hydrogen of the sulfonic acid group and the nitrogen atom of the amino group.

  14. Regenerable Air Purification System for Gas-Phase Contaminant Control

    NASA Technical Reports Server (NTRS)

    Constantinescu, Ileana C.; Finn, John E.; LeVan, M. Douglas; Lung, Bernadette (Technical Monitor)

    2000-01-01

    Tests of a pre-prototype regenerable air purification system (RAPS) that uses water vapor to displace adsorbed contaminants from an adsorbent column have been performed at NASA Ames Research Center. A unit based on this design can be used for removing trace gas-phase contaminants from spacecraft cabin air or from polluted process streams including incinerator exhaust. During the normal operation mode, contaminants are removed from the air on the column. Regeneration of the column is performed on-line. During regeneration, contaminants are displaced and destroyed inside the closed oxidation loop. In this presentation we discuss initial experimental results for the performance of RAPS in the removal and treatment of several important spacecraft contaminant species from air.

  15. Silicon Nanowire-Based Devices for Gas-Phase Sensing

    PubMed Central

    Cao, Anping; Sudhölter, Ernst J.R.; de Smet, Louis C.P.M.

    2014-01-01

    Since their introduction in 2001, SiNW-based sensor devices have attracted considerable interest as a general platform for ultra-sensitive, electrical detection of biological and chemical species. Most studies focus on detecting, sensing and monitoring analytes in aqueous solution, but the number of studies on sensing gases and vapors using SiNW-based devices is increasing. This review gives an overview of selected research papers related to the application of electrical SiNW-based devices in the gas phase that have been reported over the past 10 years. Special attention is given to surface modification strategies and the sensing principles involved. In addition, future steps and technological challenges in this field are addressed. PMID:24368699

  16. Optical properties of anthocyanins in the gas phase

    NASA Astrophysics Data System (ADS)

    Ge, Xiaochuan; Calzolari, Arrigo; Baroni, Stefano

    2015-01-01

    The gas-phase optical properties of the six most common anthocyanins are studied using time-dependent density-functional theory. Different anthocyanins are classified into three groups, according to the number of low-frequency peaks displayed in the UV-vis spectrum. This behavior is analyzed in terms of one-electron transitions and interaction effects, the latter being rationalized using a suitable double-pole model. Moving from PBE to hybrid exchange-correlation functionals results in a hypsochromic shift of the optical gap. While the colors thus predicted do not quite match those observed in solution, thus highlighting the importance of solvation effects, adoption of hybrid functionals remarkably determines a greater chromatic uniformity of different molecules, in qualitative agreement with experimental evidence in acidic solutions.

  17. Regenerable Air Purification System for Gas-Phase Contaminant Control

    NASA Technical Reports Server (NTRS)

    Constantinescu, Ileana C.; Qi, Nan; LeVan, M. Douglas; Finn, Cory K.; Finn, John E.; Luna, Bernadette (Technical Monitor)

    2000-01-01

    A regenerable air purification system (RAPS) that uses water vapor to displace adsorbed contaminants from an. adsorbent column into a closed oxidation loop is under development through cooperative R&D between Vanderbilt University and NASA Ames Research Center. A unit based on this design can be used for removing trace gas-phase contaminants from spacecraft cabin air or from polluted process streams including incinerator exhaust. Recent work has focused on fabrication and operation of a RAPS breadboard at NASA Ames, and on measurement of adsorption isotherm data for several important organic compounds at Vanderbilt. These activities support the use and validation of RAPS modeling software also under development at Vanderbilt, which will in turn be used to construct a prototype system later in the project.

  18. Mammalian reoviruses contain a myristoylated structural protein.

    PubMed Central

    Nibert, M L; Schiff, L A; Fields, B N

    1991-01-01

    The structural protein mu 1 of mammalian reoviruses was noted to have a potential N-myristoylation sequence at the amino terminus of its deduced amino acid sequence. Virions labeled with [3H]myristic acid were used to demonstrate that mu 1 is modified by an amide-linked myristoyl group. A myristoylated peptide having a relative molecular weight (Mr) of approximately 4,000 was also shown to be a structural component of virions and was concluded to represent the 4.2-kDa amino-terminal fragment of mu 1 which is generated by the same proteolytic cleavage that yields the carboxy-terminal fragment and major outer capsid protein mu 1C. The myristoylated 4,000-Mr peptide was found to be present in reovirus intermediate subviral particles but to be absent from cores, indicating that it is a component of the outer capsid. A distinct large myristoylated fragment of the intact mu 1 protein was also identified in intermediate subviral particles, but no myristoylated mu-region proteins were identified in cores, consistent with the location of mu 1 in the outer capsid. Similarities between amino-terminal regions of the reovirus mu 1 protein and the poliovirus capsid polyprotein were noted. By analogy with other viruses that contain N-myristoylated structural proteins (particularly picornaviruses), we suggest that the myristoyl group attached to mu 1 and its amino-terminal fragments has an essential role in the assembly and structure of the reovirus outer capsid and in the process of reovirus entry into cells. Images PMID:2002551

  19. Surfactants from the gas phase may promote cloud droplet formation.

    PubMed

    Sareen, Neha; Schwier, Allison N; Lathem, Terry L; Nenes, Athanasios; McNeill, V Faye

    2013-02-19

    Clouds, a key component of the climate system, form when water vapor condenses upon atmospheric particulates termed cloud condensation nuclei (CCN). Variations in CCN concentrations can profoundly impact cloud properties, with important effects on local and global climate. Organic matter constitutes a significant fraction of tropospheric aerosol mass, and can influence CCN activity by depressing surface tension, contributing solute, and influencing droplet activation kinetics by forming a barrier to water uptake. We present direct evidence that two ubiquitous atmospheric trace gases, methylglyoxal (MG) and acetaldehyde, known to be surface-active, can enhance aerosol CCN activity upon uptake. This effect is demonstrated by exposing acidified ammonium sulfate particles to 250 parts per billion (ppb) or 8 ppb gas-phase MG and/or acetaldehyde in an aerosol reaction chamber for up to 5 h. For the more atmospherically relevant experiments, i.e., the 8-ppb organic precursor concentrations, significant enhancements in CCN activity, up to 7.5% reduction in critical dry diameter for activation, are observed over a timescale of hours, without any detectable limitation in activation kinetics. This reduction in critical diameter enhances the apparent particle hygroscopicity up to 26%, which for ambient aerosol would lead to cloud droplet number concentration increases of 8-10% on average. The observed enhancements exceed what would be expected based on Köhler theory and bulk properties. Therefore, the effect may be attributed to the adsorption of MG and acetaldehyde to the gas-aerosol interface, leading to surface tension depression of the aerosol. We conclude that gas-phase surfactants may enhance CCN activity in the atmosphere.

  20. Surfactants from the gas phase may promote cloud droplet formation.

    PubMed

    Sareen, Neha; Schwier, Allison N; Lathem, Terry L; Nenes, Athanasios; McNeill, V Faye

    2013-02-19

    Clouds, a key component of the climate system, form when water vapor condenses upon atmospheric particulates termed cloud condensation nuclei (CCN). Variations in CCN concentrations can profoundly impact cloud properties, with important effects on local and global climate. Organic matter constitutes a significant fraction of tropospheric aerosol mass, and can influence CCN activity by depressing surface tension, contributing solute, and influencing droplet activation kinetics by forming a barrier to water uptake. We present direct evidence that two ubiquitous atmospheric trace gases, methylglyoxal (MG) and acetaldehyde, known to be surface-active, can enhance aerosol CCN activity upon uptake. This effect is demonstrated by exposing acidified ammonium sulfate particles to 250 parts per billion (ppb) or 8 ppb gas-phase MG and/or acetaldehyde in an aerosol reaction chamber for up to 5 h. For the more atmospherically relevant experiments, i.e., the 8-ppb organic precursor concentrations, significant enhancements in CCN activity, up to 7.5% reduction in critical dry diameter for activation, are observed over a timescale of hours, without any detectable limitation in activation kinetics. This reduction in critical diameter enhances the apparent particle hygroscopicity up to 26%, which for ambient aerosol would lead to cloud droplet number concentration increases of 8-10% on average. The observed enhancements exceed what would be expected based on Köhler theory and bulk properties. Therefore, the effect may be attributed to the adsorption of MG and acetaldehyde to the gas-aerosol interface, leading to surface tension depression of the aerosol. We conclude that gas-phase surfactants may enhance CCN activity in the atmosphere. PMID:23382211

  1. Ab initio kinetics of gas phase decomposition reactions.

    PubMed

    Sharia, Onise; Kuklja, Maija M

    2010-12-01

    The thermal and kinetic aspects of gas phase decomposition reactions can be extremely complex due to a large number of parameters, a variety of possible intermediates, and an overlap in thermal decomposition traces. The experimental determination of the activation energies is particularly difficult when several possible reaction pathways coexist in the thermal decomposition. Ab initio calculations intended to provide an interpretation of the experiment are often of little help if they produce only the activation barriers and ignore the kinetics of the decomposition process. To overcome this ambiguity, a theoretical study of a complete picture of gas phase thermo-decomposition, including reaction energies, activation barriers, and reaction rates, is illustrated with the example of the β-octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) molecule by means of quantum-chemical calculations. We study three types of major decomposition reactions characteristic of nitramines: the HONO elimination, the NONO rearrangement, and the N-NO(2) homolysis. The reaction rates were determined using the conventional transition state theory for the HONO and NONO decompositions and the variational transition state theory for the N-NO(2) homolysis. Our calculations show that the HMX decomposition process is more complex than it was previously believed to be and is defined by a combination of reactions at any given temperature. At all temperatures, the direct N-NO(2) homolysis prevails with the activation barrier at 38.1 kcal/mol. The nitro-nitrite isomerization and the HONO elimination, with the activation barriers at 46.3 and 39.4 kcal/mol, respectively, are slow reactions at all temperatures. The obtained conclusions provide a consistent interpretation for the reported experimental data. PMID:21077597

  2. Solving coiled-coil protein structures

    DOE PAGESBeta

    Dauter, Zbigniew

    2015-02-26

    With the availability of more than 100,000 entries stored in the Protein Data Bank (PDB) that can be used as search models, molecular replacement (MR) is currently the most popular method of solving crystal structures of macromolecules. Significant methodological efforts have been directed in recent years towards making this approach more powerful and practical. This resulted in the creation of several computer programs, highly automated and user friendly, that are able to successfully solve many structures even by researchers who, although interested in structures of biomolecules, are not very experienced in crystallography.

  3. Photoinduced intermolecular cross-linking of gas phase triacylglycerol lipid ions.

    PubMed

    Nie, Shuai; Pham, Huong T; Blanksby, Stephen J; Reid, Gavin E

    2015-01-01

    Complex mixtures of plant derived triglycerol (TG) lipids are commonly used as feedstock components for the production of industrial polymers. However, there remains a need for the development of analytical strategies to investigate the intrinsic intermolecular cross-linking reactivity of individual TG molecules within these mixtures as a function of their structures and physicochemical properties, and for the characterization of the resultant products. Here, to address this need, we describe a novel multistage tandem mass spectrometry based method for intermolecular cross-linking and subsequent structural characterization of TG lipid ions in the gas phase. Cross-linking reactions were initiated using 266 nm ultraviolet photodissociation tandem mass spectrometry (UVPD-MS/MS) of saturated or unsaturated TG dimers introduced via electrospray ionization into a linear ion trap mass spectrometer as noncovalent complexes with protonated 3,4-, 2,4- or 3,5- diiodoaniline (diIA). UVPD resulted in the initial formation of an anilinyl biradical via the sequential loss of two iodine radicals, which underwent further reaction to yield multiple cross-linked TG products along with competing noncross-linking processes. These chemistries are proposed to occur via sequential combinations of hydrogen abstraction (H-abstraction), radical addition and radical recombination. Multistage collision induced dissociation tandem mass spectrometry (CID-MS(n)) was used to obtain evidence for the structures and mechanisms of formation for these products, as a function of both the TG lipid and diIA ion structures. The efficiency of the UVPD reaction was shown to be dependent on the number of unsaturation sites present within the TG lipids. However, when unsaturation sites were present, formation of the cross-linked and noncross-linked product ions via H-abstraction and radical addition mechanisms was found to be competitive. Finally, the identity of the anilinyl biradical (e.g., 3,4- versus 2

  4. Simulations of kinetically irreversible protein aggregate structure.

    PubMed Central

    Patro, S Y; Przybycien, T M

    1994-01-01

    We have simulated the structure of kinetically irreversible protein aggregates in two-dimensional space using a lattice-based Monte-Carlo routine. Our model specifically accounts for the intermolecular interactions between hydrophobic and hydrophilic protein surfaces and a polar solvent. The simulations provide information about the aggregate density, the types of inter-monomer contacts and solvent content within the aggregates, the type and extent of solvent exposed perimeter, and the short- and long-range order all as a function of (i) the extent of monomer hydrophobic surface area and its distribution on the model protein surface and (ii) the magnitude of the hydrophobic-hydrophobic contact energy. An increase in the extent of monomer hydrophobic surface area resulted in increased aggregate densities with concomitant decreased system free energies. These effects are accompanied by increases in the number of hydrophobic-hydrophobic contacts and decreases in the solvent-exposed hydrophobic surface area of the aggregates. Grouping monomer hydrophobic surfaces in a single contiguous stretch resulted in lower aggregate densities and lower short range order. More favorable hydrophobic-hydrophobic contact energies produced structures with higher densities but the number of unfavorable protein-protein contacts was also observed to increase; greater configurational entropy produced the opposite effect. Properties predicted by our model are in good qualitative agreement with available experimental observations. Images FIGURE 6 FIGURE 13 PMID:8061184

  5. Exploiting Microbeams for Membrane Protein Structure Determination.

    PubMed

    Warren, Anna J; Axford, Danny; Paterson, Neil G; Owen, Robin L

    2016-01-01

    A reproducible, and sample independent means of predictably obtaining large, well-ordered crystals has proven elusive in macromolecular crystallography. In the structure determination pipeline, crystallisation often proves to be a rate-limiting step, and the process of obtaining even small or badly ordered crystals can prove time-consuming and laborious. This is particularly true in the field of membrane protein crystallography and this is reflected in the limited number of unique membrane protein structures deposited in the protein data bank (less than 650 by June 2016 - http://blanco.biomol.uci.edu/mpstruc ). Over recent years the requirement for, and time and cost associated with obtaining, large crystals has been partially alleviated through the development of beamline instrumentation allowing data collection, and structure solution, from ever-smaller crystals. Advances in several areas have led to a step change in what might be considered achievable during a synchrotron trip over the last decade. This chapter will briefly review the current status of the field, the tools available to ease data collection and processing, and give some examples of exploitation of these for membrane protein microfocus macromolecular crystallography. PMID:27553238

  6. Photoinduced structural changes to protein kinase A

    NASA Astrophysics Data System (ADS)

    Rozinek, Sarah C.; Thomas, Robert J.; Brancaleon, Lorenzo

    2014-03-01

    The importance of porphyrins in organisms is underscored by the ubiquitous biological and biochemical functions that are mediated by these compounds and by their potential biomedical and biotechnological applications. Protoporphyrin IX (PPIX) is the precursor to heme and has biomedical applications such as its use as a photosensitizer in phototherapy and photodetection of cancer. Among other applications, our group has demonstrated that low-irradiance exposure to laser irradiation of PPIX, Fe-PPIX, or meso-tetrakis (4-sulfonatophenyl) porphyrin (TSPP) non-covalently docked to a protein causes conformational changes in the polypeptide. Such approach can have remarkable consequences in the study of protein structure/function relationship and can be used to prompt non-native protein properties. Therefore we have investigated protein kinase A (PKA), a more relevant protein model towards the photo-treatment of cancer. PKA's enzymatic functions are regulated by the presence of cyclic adenosine monophosphate for intracellular signal transduction involved in, among other things, stimulation of transcription, tumorigenesis in Carney complex and migration of breast carcinoma cells. Since phosphorylation is a necessary step in some cancers and inflammatory diseases, inhibiting the protein kinase, and therefore phosphorylation, may serve to treat these diseases. Changes in absorption, steady-state fluorescence, and fluorescence lifetime indicate: 1) both TSPP and PPIX non-covalently bind to PKA where they maintain photoreactivity; 2) absorptive photoproduct formation occurs only when PKA is bound to TSPP and irradiated; and 3) PKA undergoes secondary structural changes after irradiation with either porphyrin bound. These photoinduced changes could affect the protein's enzymatic and signaling capabilities.

  7. Electronic structure of bacterial surface protein layers

    SciTech Connect

    Maslyuk, Volodymyr V.; Mertig, Ingrid; Bredow, Thomas; Mertig, Michael; Vyalikh, Denis V.; Molodtsov, Serguei L.

    2008-01-15

    We report an approach for the calculation of the electronic density of states of the dried two-dimensional crystalline surface protein layer (S layer) of the bacterium Bacillus sphaericus NCTC 9602. The proposed model is based on the consideration of individual amino acids in the corresponding conformation of the peptide chain which additively contribute to the electronic structure of the entire protein complex. The derived results agree well with the experimental data obtained by means of photoemission (PE), resonant PE, and near-edge x-ray absorption spectroscopy.

  8. Proteomic investigation of natural killer cell microsomes using gas-phase fractionation by mass spectrometry.

    PubMed

    Blonder, Josip; Rodriguez-Galan, Maria Cecilia; Lucas, David A; Young, Howard A; Issaq, Haleem J; Veenstra, Timothy D; Conrads, Thomas P

    2004-04-01

    We have explored the utility of gas-phase fractionation by mass spectrometry (MS) in the mass-to-charge (m/z) dimension (GPF(m/z)) for increasing the effective number of protein identifications in cases where sample quantity limits the use of multi-dimensional chromatographic fractionation. A peptide digestate from proteins isolated from the membrane fraction of natural killer (NK) cells was analyzed by microcapillary reversed-phase liquid chromatography coupled online to an ion-trap (IT) mass spectrometer. Performing GPF(m/z) using eight narrow precursor ion scan m/z ranges enabled the identification of 340 NK cell proteins from 12 microg of digestate, representing more than a fivefold increase in the number of proteins identified as compared to the same experiment employing a standard precursor ion survey scan m/z range (i.e., m/z 400-2000). The results show that GPF(m/z) represents an effective technique for increasing protein identifications in global proteomic investigations especially when sample quantity is limited.

  9. Separation of important new platelet glycoproteins (GPIa, GPIc, GPIc*, GPIIa and GMP-140) by f.p.l.c. Characterization by monoclonal antibodies and gas-phase sequencing.

    PubMed

    Catimel, B; Parmentier, S; Leung, L L; McGregor, J L

    1991-10-15

    A large number of membrane glycoproteins (around 40) are present on the surface of human blood platelets. Some of these glycoproteins are expressed in relatively small amounts, and their functions, as well as their structure, remain to be elucidated. The aim of the present study was to separate rapidly, under non-denaturing conditions, and characterize minor glycoproteins such as Very Late Antigens (VLA) (GPIa, GPIc, GPIc* and GPIIa) and GMP-140 (also known as PADGEM). VLAs and GMP-140 are respectively members of the integrin and selectin families. Platelet membrane glycoproteins were separated by wheat-germ agglutinin lectin affinity and Mono Q anion-exchange f.p.l.c. Peaks bearing isolated glycoproteins were electrophoresed on one- or two-dimensional SDS/polyacrylamide gels, Western blotted on to Immobilon poly(vinylidene difluoride) membranes and gas-phase-sequenced. The identity of isolated glycoproteins was also obtained by the use of monoclonal or polyclonal antibodies and tryptic peptide maps. Five minor [GPIa, GPIc, GPIc*, GPIIa and GMP 140 (PADGEM)], as well as a major (GPIIIb) glycoprotein, were eluted at low salt concentrations. GPIIb-IIIa and GPIb were eluted at high salt concentrations. The N-terminal sequence of platelet GPIa was identical with that obtained by Takada & Hemler [(1989) J. Cell Biol. 109, 397-407]. However, the N-terminal sequence of platelet GPIc + Ic* and GPIIa were found to differ from those deduced from cDNA sequences isolated from human placenta or umbilical-vein endothelial-cell cDNA libraries. The combined use of f.p.l.c. and gas-phase sequencing techniques provides a very powerful tool to separate and characterize rapidly platelet or other cellular proteins for structural, immunological and functional studies.

  10. Far-Ir Spectroscopy of Neutral Gas Phase Peptides: Signatures from Combined Experiments and Simulations

    NASA Astrophysics Data System (ADS)

    Mahé, Jérôme; Gaigeot, Marie-Pierre; Bakker, Daniël; Jaeqx, Sander; Rijs, Anouk

    2016-06-01

    Within the past two decades, action vibrational spectroscopy has become an almost routine experimental method to probe the structures of molecules and clusters in the gas phase (neutral and ions). Such experiments are mainly performed in the 1000-4000 wn fingerprint regions. Though successful in many respects, these spectral domains can be however restrictive in the information provided, and sometimes reach limitations for unravelling structures without ambiguity. In a collaborative work with the group of Dr A.M. Rijs (FELIX laboratory, Radbout University, The Netherlands) we have launched a new strategy where the far-IR/Tera-Hertz domain (100-800 wn domain) is experimentally probed for neutral gas phase molecules. Our group in Paris apply finite temperature DFT-based molecular dynamics (DFT-MD) simulations in order to unravel the complex signatures arising in the far-IR domain, and provide an unambiguous assignment both of the structural conformation of the gas phase molecules (taking into account the experimental conditions) and an understanding of the spectral signatures/fingerprints. We will discuss our experimental and theoretical investigations on two neutral peptides in the 100-800 wn far-IR spectral domain, i.e. Z-Ala6 and PheGly dipeptide, that represent two systems which definitive conformational assignment was not possible without the far IR signatures. We will also present our very recent results on the Phe-X peptide series, where X stands for Gly, Ala, Pro, Val, Ser, Cys, combining experiments and DFT-MD simulations, providing a detailed understanding of the vibrational fingerprints in the far-IR domain. In all exemples, we will show how DFT-MD simulations is the proper theoretical tool to account for vibrational anharmonicities and mode couplings, of prime importance in the far-IR domain. References : J. Mahé, S. Jaeqx, A.M. Rijs, M.P. Gaigeot, Phys. Chem. Chem. Phys., 17 :25905 (2015) S. Jaeqx, J. Oomens, A. Cimas, M.P. Gaigeot, A.M. Rijs, Angew

  11. Gas-phase lithium cation basicity of histamine and its agonist 2-([beta]-aminoethyl)-pyridine

    NASA Astrophysics Data System (ADS)

    Hallmann, M.; Raczynska, E. D.; Gal, J. F.; Maria, P. C.

    2007-11-01

    The gas-phase lithium cation basicities (LCBs) were obtained for histamine (HA) and its agonist 2-([beta]-aminoethyl)-pyridine (AEP) from collision-induced dissociation of lithium adducts using Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). For measurements, MeO(CH2)2OMe, Et3PO and (Me2N)3PO (HMPA) were used as the reference compounds. The experimental LCB of AEP was located between those of Et3PO and (Me2N)3PO. The experimental LCB of HA was found to be higher than those of AEP and HMPA by more than 2 kcal mol-1 clearly indicating that the LCB of HA is higher than any LCB for a neutral base yet measured (crown-ethers excepted). The experimental LCBs of the parent bases (pyridine and imidazole) are lower by more than 10 kcal mol-1. In parallel, DFT calculations {B3LYP/6-31G*//B3LYP/6-31G* and B3LYP/6-311+G**//B3LYP/6-31G*} were performed for HA, AEP and their lithium adducts. Among the 22 reasonable conformations of the HA-Li+ adduct, only one appears to be significantly more stable than the others. This is also the case for one structure among seven conformations of the AEP-Li+ adduct. These two stable structures have the [`]scorpion' conformation, in which the Li+ cation is almost equally chelated by two basic nitrogen atoms, the ring N-aza and the chain N-amino. Other HA-Li+ and AEP-Li+ conformations have noticeably higher energies than the [`]scorpion' structures. The difference between the DFT calculated LCBs of HA and AEP (about 4 kcal mol-1) is in agreement with that experimentally obtained (>2 kcal mol-1). The high experimental and theoretical values of LCB for HA and AEP militate in favor of a strong chelation of Li+ by both ligands in the gas-phase. This chelation effect was also evidenced previously for the proton gas-phase basicity.

  12. Generation and Characterization of a Distonic Biradical Anion Formed from an Enediynone Prodrug in the Gas Phase

    PubMed Central

    Yang, Linan; Bekele, Tefsit; Lipton, Mark A.

    2013-01-01

    A negatively charged biradical intermediate was successfully generated in the gas phase via cyclization of the deprotonated bicyclo[8.3.0]trideca-12-ene-2,7-diyn-1-one precursor. The inherent negative charge of this biradical allows its characterization via collision-activated dissociation and reactions with a variety of neutral substrates in an FT-ICR mass spectrometer. Although the biradical is unreactive toward reagents that usually react rapidly with positively charged biradicals, such as dimethyl disulfide, it reacts with the halogen-containing substrates carbon tetrachloride, carbon tetrabromide and bromotrichloromethane via bromine or chlorine atom abstraction, which supports its biradical structure. The results presented in this study indicate that cyclizations commonly used in solution to form biradical intermediates from enediyne compounds may also occur in the gas phase. PMID:23512422

  13. Amide-I and -II vibrations of the cyclic beta-sheet model peptide gramicidin S in the gas phase.

    PubMed

    Kupser, Peter; Pagel, Kevin; Oomens, Jos; Polfer, Nick; Koksch, Beate; Meijer, Gerard; von Helden, Gert

    2010-02-17

    In the condensed phase, the peptide gramicidin S is often considered as a model system for a beta-sheet structure. Here, we investigate gramicidin S free of any influences of the environment by measuring the mid-IR spectra of doubly protonated (deuterated) gramicidin S in the gas phase. In the amide I (i.e., C=O stretch) region, the spectra show a broad split peak between 1580 and 1720 cm(-1). To deduce structural information, the conformational space has been searched using molecular dynamics methods and several structural candidates have been further investigated at the density functional level. The calculations show the importance of the interactions of the charged side-chains with the backbone, which is responsible for the lower frequency part of the amide I peak. When this interaction is inhibited via complexation with two 18-crown-6 molecules, the amide I peak narrows and shows two maxima at 1653 and 1680 cm(-1). A comparison to calculations shows that for this complexed ion, four C=O groups are in an antiparallel beta-sheet arrangement. Surprisingly, an analysis of the calculated spectra shows that these beta-sheet C=O groups give rise to the vibrations near 1680 cm(-1). This is in sharp contrast to expectations based on values for the condensed phase, where resonances of beta-sheet sections are thought to occur near 1630 cm(-1). The difference between those values might be caused by interactions with the environment, as the condensed phase value is mostly deduced for beta-sheet sections that are embedded in larger proteins, that interact strongly with solvent or that are part of partially aggregated species.

  14. Foldons, Protein Structural Modules, and Exons

    NASA Astrophysics Data System (ADS)

    Panchenko, Anna R.; Luthey-Schulten, Zaida; Wolynes, Peter G.

    1996-03-01

    Foldons, which are kinetically competent, quasi-independently folding units of a protein, may be defined using energy landscape analysis. Foldons can be identified by maxima in a scan of the ratio of a contiguous segment's energetic stability gap to the energy variance of that segment's molten globule states, reflecting the requirement of minimal frustration. The predicted foldons are compared with the exons and structural modules for 16 of the 30 proteins studied. Statistical analysis indicates a strong correlation between the energetically determined foldons and Go's geometrically defined structural modules, but there are marked sequence-dependent effects. There is only a weak correlation of foldons to exons. For γ II-crystallin, myoglobin, barnase, α -lactalbumin, and cytochrome c the foldons and some noncontiguous clusters of foldons compare well with intermediates observed in experiment.

  15. Structural Determinants of Misfolding in Multidomain Proteins

    PubMed Central

    Tian, Pengfei; Best, Robert B.

    2016-01-01

    Recent single molecule experiments, using either atomic force microscopy (AFM) or Förster resonance energy transfer (FRET) have shown that multidomain proteins containing tandem repeats may form stable misfolded structures. Topology-based simulation models have been used successfully to generate models for these structures with domain-swapped features, fully consistent with the available data. However, it is also known that some multidomain protein folds exhibit no evidence for misfolding, even when adjacent domains have identical sequences. Here we pose the question: what factors influence the propensity of a given fold to undergo domain-swapped misfolding? Using a coarse-grained simulation model, we can reproduce the known propensities of multidomain proteins to form domain-swapped misfolds, where data is available. Contrary to what might be naively expected based on the previously described misfolding mechanism, we find that the extent of misfolding is not determined by the relative folding rates or barrier heights for forming the domains present in the initial intermediates leading to folded or misfolded structures. Instead, it appears that the propensity is more closely related to the relative stability of the domains present in folded and misfolded intermediates. We show that these findings can be rationalized if the folded and misfolded domains are part of the same folding funnel, with commitment to one structure or the other occurring only at a relatively late stage of folding. Nonetheless, the results are still fully consistent with the kinetic models previously proposed to explain misfolding, with a specific interpretation of the observed rate coefficients. Finally, we investigate the relation between interdomain linker length and misfolding, and propose a simple alchemical model to predict the propensity for domain-swapped misfolding of multidomain proteins. PMID:27163669

  16. Protein Structure Prediction with Evolutionary Algorithms

    SciTech Connect

    Hart, W.E.; Krasnogor, N.; Pelta, D.A.; Smith, J.

    1999-02-08

    Evolutionary algorithms have been successfully applied to a variety of molecular structure prediction problems. In this paper we reconsider the design of genetic algorithms that have been applied to a simple protein structure prediction problem. Our analysis considers the impact of several algorithmic factors for this problem: the confirmational representation, the energy formulation and the way in which infeasible conformations are penalized, Further we empirically evaluated the impact of these factors on a small set of polymer sequences. Our analysis leads to specific recommendations for both GAs as well as other heuristic methods for solving PSP on the HP model.

  17. Protein structural dynamics at the gas/water interface examined by hydrogen exchange mass spectrometry.

    PubMed

    Xiao, Yiming; Konermann, Lars

    2015-08-01

    Gas/water interfaces (such as air bubbles or foam) are detrimental to the stability of proteins, often causing aggregation. This represents a potential problem for industrial processes, for example, the production and handling of protein drugs. Proteins possess surfactant-like properties, resulting in a high affinity for gas/water interfaces. The tendency of previously buried nonpolar residues to maximize contact with the gas phase can cause significant structural distortion. Most earlier studies in this area employed spectroscopic tools that could only provide limited information. Here we use hydrogen/deuterium exchange (HDX) mass spectrometry (MS) for probing the conformational dynamics of the model protein myoglobin (Mb) in the presence of N(2) bubbles. HDX/MS relies on the principle that unfolded and/or highly dynamic regions undergo faster deuteration than tightly folded segments. In bubble-free solution Mb displays EX2 behavior, reflecting the occurrence of short-lived excursions to partially unfolded conformers. A dramatically different behavior is seen in the presence of N(2) bubbles; EX2 dynamics still take place, but in addition the protein shows EX1 behavior. The latter results from interconversion of the native state with conformers that are globally unfolded and long-lived. These unfolded species likely correspond to Mb that is adsorbed to the surface of gas bubbles. N(2) sparging also induces aggregation. To explain the observed behavior we propose a simple model, that is, "semi-unfolded" ↔ "native" ↔ "globally unfolded" → "aggregated". This model quantitatively reproduces the experimentally observed kinetics. To the best of our knowledge, the current study marks the first exploration of surface denaturation phenomena by HDX/MS. PMID:25761782

  18. Protein structural dynamics at the gas/water interface examined by hydrogen exchange mass spectrometry

    PubMed Central

    Xiao, Yiming; Konermann, Lars

    2015-01-01

    Gas/water interfaces (such as air bubbles or foam) are detrimental to the stability of proteins, often causing aggregation. This represents a potential problem for industrial processes, for example, the production and handling of protein drugs. Proteins possess surfactant-like properties, resulting in a high affinity for gas/water interfaces. The tendency of previously buried nonpolar residues to maximize contact with the gas phase can cause significant structural distortion. Most earlier studies in this area employed spectroscopic tools that could only provide limited information. Here we use hydrogen/deuterium exchange (HDX) mass spectrometry (MS) for probing the conformational dynamics of the model protein myoglobin (Mb) in the presence of N2 bubbles. HDX/MS relies on the principle that unfolded and/or highly dynamic regions undergo faster deuteration than tightly folded segments. In bubble-free solution Mb displays EX2 behavior, reflecting the occurrence of short-lived excursions to partially unfolded conformers. A dramatically different behavior is seen in the presence of N2 bubbles; EX2 dynamics still take place, but in addition the protein shows EX1 behavior. The latter results from interconversion of the native state with conformers that are globally unfolded and long-lived. These unfolded species likely correspond to Mb that is adsorbed to the surface of gas bubbles. N2 sparging also induces aggregation. To explain the observed behavior we propose a simple model, that is, “semi-unfolded” ↔ “native” ↔ “globally unfolded” → “aggregated”. This model quantitatively reproduces the experimentally observed kinetics. To the best of our knowledge, the current study marks the first exploration of surface denaturation phenomena by HDX/MS. PMID:25761782

  19. Automated gas-phase purification for accurate, multiplexed quantification on a stand-alone ion trap mass spectrometer

    PubMed Central

    Vincent, Catherine E.; Rensvold, Jarred W.; Westphall, Michael S.; Pagliarini, David J.; Coon, Joshua J.

    2012-01-01

    Isobaric tagging enables the acquisition of highly-multiplexed proteome quantification but is hindered by the pervasive problem of precursor interference. The elimination of co-isolated contaminants prior to reporter tag generation can be achieved through the use of gas-phase purification via proton transfer ion/ion reactions (QuantMode); however, the original QuantMode technique was implemented on the high resolution linear ion trap-Orbitrap hybrid mass spectrometer enabled with electron transfer dissociation (ETD). Here we extend this technology to stand-alone linear ion trap systems (trapQuantMode). Facilitated by the use of inlet beam-type activation (i.e., trapHCD) for production and observation of the low mass-to-charge reporter region, this scan sequence comprises three separate events to maximize peptide identifications, minimize duty cycle requirements, and increase quantitative accuracy, precision, and dynamic range. Significant improvements in quantitative accuracy were attained over standard methods when using trapQuantMode (trapQM) to analyze an interference model system comprising tryptic peptides of yeast that we contaminated with human peptides. Finally, we demonstrate practical benefits of this method by analysis of the proteomic changes that occur during mouse skeletal muscle myoblast differentiation. While trapQM’s reduced duty cycle led to the identification of fewer proteins than conventional operation (4,050 vs. 2,964), trapQM identified more significant differences (>1.5 fold, 1,362 vs 1,132, respectively; P<0.05) between the proteomes of undifferentiated myoblasts and differentiated myotubes and nearly ten-fold more differences with changes greater than 5-fold (96 vs. 12). We further show that our trapQM dataset is superior for identifying changes in protein abundance that are consistent with the metabolic and structural changes known to accompany myotube formation. PMID:23046161

  20. The origin of consistent protein structure refinement from structural averaging.

    PubMed

    Park, Hahnbeom; DiMaio, Frank; Baker, David

    2015-06-01

    Recent studies have shown that explicit solvent molecular dynamics (MD) simulation followed by structural averaging can consistently improve protein structure models. We find that improvement upon averaging is not limited to explicit water MD simulation, as consistent improvements are also observed for more efficient implicit solvent MD or Monte Carlo minimization simulations. To determine the origin of these improvements, we examine the changes in model accuracy brought about by averaging at the individual residue level. We find that the improvement in model quality from averaging results from the superposition of two effects: a dampening of deviations from the correct structure in the least well modeled regions, and a reinforcement of consistent movements towards the correct structure in better modeled regions. These observations are consistent with an energy landscape model in which the magnitude of the energy gradient toward the native structure decreases with increasing distance from the native state.

  1. Preparation and study of the Fe sub 2 sup + -benzyne ion in the gas phase

    SciTech Connect

    Huang, Yongqing; Freiser, B.S. )

    1990-03-07

    The results of a study of the preparation and reactivity of the Fe{sup +}{sub 2}-benzyne ion in the gas phase is reported herein. This study continues the investigation into the reactivity of transition-metal dinuclear ions as compared with their constituent monoatomic ionic species. The enhanced reactivity of Fe{sup +}{sub 2}-benzyne over the Fe{sub 2}{sup +} is thought to be due to two effects: (1) the ligand polarizes or in some way changes the electronic structure of the metal center to prevent oxidative addition and (2) the combination of the highly unsaturated benzyne ligand provides a very efficient pathway for further reaction steps following initial metal center oxidative insertion. 24 refs., 1 tab.

  2. Thermodynamic and kinetic stability of zwitterionic histidine: Effects of gas phase hydration

    NASA Astrophysics Data System (ADS)

    Lee, Sung-Sik; Kim, Ju-Young; Han, Yuna; Shim, Hyun-Jin; Lee, Sungyul

    2015-09-01

    We present calculations for histidine-(H2O)n (n = 0-6) to examine the effects of micro-hydrating water molecules on the relative stability of the zwitterionic vs. canonical forms of histidine. We calculate the structures and Gibbs free energies of the conformers at wB97XD/6-311++G(d,p) level of theory. We find that six water molecules are required to produce the thermodynamically stable histidine zwitterion. By calculating the barriers of canonical ↔ zwitterionic transformation, we predict that both the most stable canonical and zwitterionic forms of histidine-(H2O)6 may be observed in low temperature gas phase environment.

  3. Effect of trehalose on protein structure

    PubMed Central

    Jain, Nishant Kumar; Roy, Ipsita

    2009-01-01

    Trehalose is a ubiquitous molecule that occurs in lower and higher life forms but not in mammals. Till about 40 years ago, trehalose was visualized as a storage molecule, aiding the release of glucose for carrying out cellular functions. This perception has now changed dramatically. The role of trehalose has expanded, and this molecule has now been implicated in a variety of situations. Trehalose is synthesized as a stress-responsive factor when cells are exposed to environmental stresses like heat, cold, oxidation, desiccation, and so forth. When unicellular organisms are exposed to stress, they adapt by synthesizing huge amounts of trehalose, which helps them in retaining cellular integrity. This is thought to occur by prevention of denaturation of proteins by trehalose, which would otherwise degrade under stress. This explanation may be rational, since recently, trehalose has been shown to slow down the rate of polyglutamine-mediated protein aggregation and the resultant pathogenesis by stabilizing an aggregation-prone model protein. In recent years, trehalose has also proved useful in the cryopreservation of sperm and stem cells and in the development of a highly reliable organ preservation solution. This review aims to highlight the changing perception of the role of trehalose over the last 10 years and to propose common mechanisms that may be involved in all the myriad ways in which trehalose stabilizes protein structures. These will take into account the structure of trehalose molecule and its interactions with its environment, and the explanations will focus on the role of trehalose in preventing protein denaturation. PMID:19177348

  4. Full field gas phase velocity measurements in microgravity

    NASA Technical Reports Server (NTRS)

    Griffin, Devon W.; Yanis, William

    1995-01-01

    Measurement of full-field velocities via Particle Imaging Velocimetry (PIV) is common in research efforts involving fluid motion. While such measurements have been successfully performed in the liquid phase in a microgravity environment, gas-phase measurements have been beset by difficulties with seeding and laser strength. A synthesis of techniques developed at NASA LeRC exhibits promise in overcoming these difficulties. Typical implementation of PIV involves forming the light from a pulsed laser into a sheet that is some fraction of a millimeter thick and 50 or more millimeters wide. When a particle enters this sheet during a pulse, light scattered from the particle is recorded by a detector, which may be a film plane or a CCD array. Assuming that the particle remains within the boundaries of the sheet for the second pulse and can be distinguished from neighboring particles, comparison of the two images produces an average velocity vector for the time between the pulses. If the concentration of particles in the sampling volume is sufficiently large but the particles remain discrete, a full field map may be generated.

  5. Surface plasmon sensing of gas phase contaminants using optical fiber.

    SciTech Connect

    Thornberg, Steven Michael; White, Michael I.; Rumpf, Arthur Norman; Pfeifer, Kent Bryant

    2009-10-01

    Fiber-optic gas phase surface plasmon resonance (SPR) detection of several contaminant gases of interest to state-of-health monitoring in high-consequence sealed systems has been demonstrated. These contaminant gases include H{sub 2}, H{sub 2}S, and moisture using a single-ended optical fiber mode. Data demonstrate that results can be obtained and sensitivity is adequate in a dosimetric mode that allows periodic monitoring of system atmospheres. Modeling studies were performed to direct the design of the sensor probe for optimized dimensions and to allow simultaneous monitoring of several constituents with a single sensor fiber. Testing of the system demonstrates the ability to detect 70mTorr partial pressures of H{sub 2} using this technique and <280 {micro}Torr partial pressures of H{sub 2}S. In addition, a multiple sensor fiber has been demonstrated that allows a single fiber to measure H{sub 2}, H{sub 2}S, and H{sub 2}O without changing the fiber or the analytical system.

  6. Gas phase plasma impact on phenolic compounds in pomegranate juice.

    PubMed

    Herceg, Zoran; Kovačević, Danijela Bursać; Kljusurić, Jasenka Gajdoš; Jambrak, Anet Režek; Zorić, Zoran; Dragović-Uzelac, Verica

    2016-01-01

    The aim of the study was to evaluate the effect of gas phase plasma on phenolic compounds in pomegranate juice. The potential of near infrared reflectance spectroscopy combined with partial least squares for monitoring the stability of phenolic compounds during plasma treatment was explored, too. Experiments are designed to investigate the effect of plasma operating conditions (treatment time 3, 5, 7 min; sample volume 3, 4, 5 cm(3); gas flow 0.75, 1, 1.25 dm(3) min(-1)) on phenolic compounds and compared to pasteurized and untreated pomegranate juice. Pasteurization and plasma treatment resulted in total phenolic content increasing by 29.55% and 33.03%, respectively. Principal component analysis and sensitivity analysis outputted the optimal treatment design with plasma that could match the pasteurized sample concerning the phenolic stability (5 min/4 cm(3)/0.75 dm(3) min(-1)). Obtained results demonstrate the potential of near infrared reflectance spectroscopy that can be successfully used to evaluate the quality of pomegranate juice upon plasma treatment considering the phenolic compounds.

  7. Gas-phase study of Fe sup + -benzyne with alkanes

    SciTech Connect

    Yongqing Huang; Freiser, B.S. )

    1989-03-29

    The unimolecular chemistry of Fe{sup +}-benzyne and its reactivity with small alkanes in the gas phase are studied by Fourier transform mass spectrometry (FTMS). Collision-induced dissociation of Fe{sup +}-benzyne yields benzyne loss exclusively. In contrast, photodissociation of Fe{sup +}-benzyne yields not only cleavage of benzyne from Fe{sup +}, but competitive loss of C{sub 2}H{sub 2} and C{sub 4}H{sub 2} as well. The Fe{sup +}-benzyne is formed from chlorobenzene by loss of HCl. This dehydrochlorination of chlorobenzene also occurs in secondary reactions up to six times forming products of the type Fe{sup +}-polyphenylene. Fe{sup +}-benzyne reacts with alkanes larger than methane to form a wide variety of product ions by mechanisms including hydrogenation and methanation of the benzyne ligand. All of the product ions can be explained by mechanisms based on Fe{sup +} insertion into either C-C or C-H bonds as the reaction-initiating step, followed by either alkyl or H migration from Fe{sup +} onto the benzyne ligand or, alternatively, by the migratory insertion of benzyne into a metal-carbon or metal-hydrogen bond. Photodissociation and ion-molecule reaction studies yield a value for the metal-ligand bond energy of D{degree} (Fe{sup +}-benzyne) = 76 {plus minus} 10 kcal/mol.

  8. Estimation of gas phase mixing in packed beds

    SciTech Connect

    Frigerio, S.; Thunman, H.; Leckner, B.; Hermansson, S.

    2008-04-15

    An improved model is presented for estimation of the mixing of gaseous species in a packed bed for fuel conversion. In particular, this work clarifies the main characteristics of mixing of volatiles and oxidizers in a burning bed of high-volatile solid fuel. Expressions are introduced to represent the active role of degradation of the solid particles in the mixing within the gas phase. During drying and devolatilization the solids modify the behavior of the gas flow: the volatiles released from the surface of the particles increase the turbulence in the system, and hence the rates of the homogeneous reactions under mixing-limited conditions. Numerical experiments are carried out to test the validity of this conclusion regarding mixing in different geometries. The flow of volatiles leaving the fuel particles is shown to contribute significantly to mixing, especially at low air flows through a bed. However, the fraction of the particle surface where volatiles are released and its orientation in the bed should be better determined in order to increase the accuracy of the estimates of turbulent mixing. (author)

  9. Project ARGO: Gas phase formation in simulated microgravity

    NASA Technical Reports Server (NTRS)

    Powell, Michael R.; Waligora, James M.; Norfleet, William T.; Kumar, K. Vasantha

    1993-01-01

    The ARGO study investigated the reduced incidence of joint pain decompression sickness (DCS) encountered in microgravity as compared with an expected incidence of joint pain DCS experienced by test subjects in Earth-based laboratories (unit gravity) with similar protocols. Individuals who are decompressed from saturated conditions usually acquire joint pain DCS in the lower extremities. Our hypothesis is that the incidence of joint pain DCS can be limited by a significant reduction in the tissue gas micronuclei formed by stress-assisted nucleation. Reductions in dynamic and kinetic stresses in vivo are linked to hypokinetic and adynamic conditions of individuals in zero g. We employed the Doppler ultrasound bubble detection technique in simulated microgravity studies to determine quantitatively the degree of gas phase formation in the upper and lower extremities of test subjects during decompression. We found no evidence of right-to-left shunting through pulmonary vasculature. The volume of gas bubble following decompression was examined and compared with the number following saline contrast injection. From this, we predict a reduced incidence of DCS on orbit, although the incidence of predicted mild DCS still remains larger than that encountered on orbit.

  10. Experimental Determination of Gas Phase Thermodynamic Properties of Bimolecular Complexes

    NASA Astrophysics Data System (ADS)

    Hansen, Anne S.; Maroun, Zeina; Mackeprang, Kasper; Kjaergaard, Henrik G.

    2016-06-01

    Accurate determination of the atmospheric abundance of hydrogen bound bimolecular complexes is necessary, as hydrogen bonds are partly responsible for the formation and growth of aerosol particles. The abundance of a complex is related to the Gibbs free energy of complex formation (Δ G), which is often obtained from quantum chemical calculations that rely on calculated values of the enthalpy (Δ H) and entropy (Δ S) of complex formation. However, calculations of Δ H and in particular Δ S are associated with large uncertainties, and accurate experimental values are therefore crucial for theoretical benchmarking studies. Infrared measurements of gas phase hydrogen bound complexes were performed in the 300 to 373 K range, and lead to a purely experimental determination of Δ H using the van't Hoff equation. Equilibrium constants were determined by combining an experimental and calculated OH-stretching intensity, from which values of Δ G and hence Δ S could be determined. Thus we can determine Δ G, Δ H and Δ S for a bimolecular complex. We find that in the 300 to 373 K temperature range the determined Δ H and Δ S values are independent of temperature.

  11. Efficient Covalent Bond Formation in Gas-Phase Peptide-Peptide Ion Complexes with the Photoleucine Stapler

    NASA Astrophysics Data System (ADS)

    Shaffer, Christopher J.; Andrikopoulos, Prokopis C.; Řezáč, Jan; Rulíšek, Lubomír; Tureček, František

    2016-04-01

    Noncovalent complexes of hydrophobic peptides GLLLG and GLLLK with photoleucine (L*) tagged peptides G(L* n L m )K (n = 1,3, m = 2,0) were generated as singly charged ions in the gas phase and probed by photodissociation at 355 nm. Carbene intermediates produced by photodissociative loss of N2 from the L* diazirine rings underwent insertion into X-H bonds of the target peptide moiety, forming covalent adducts with yields reaching 30%. Gas-phase sequencing of the covalent adducts revealed preferred bond formation at the C-terminal residue of the target peptide. Site-selective carbene insertion was achieved by placing the L* residue in different positions along the photopeptide chain, and the residues in the target peptide undergoing carbene insertion were identified by gas-phase ion sequencing that was aided by specific 13C labeling. Density functional theory calculations indicated that noncovalent binding to GL*L*L*K resulted in substantial changes of the (GLLLK + H)+ ground state conformation. The peptide moieties in [GL*L*LK + GLLLK + H]+ ion complexes were held together by hydrogen bonds, whereas dispersion interactions of the nonpolar groups were only secondary in ground-state 0 K structures. Born-Oppenheimer molecular dynamics for 100 ps trajectories of several different conformers at the 310 K laboratory temperature showed that noncovalent complexes developed multiple, residue-specific contacts between the diazirine carbons and GLLLK residues. The calculations pointed to the substantial fluidity of the nonpolar side chains in the complexes. Diazirine photochemistry in combination with Born-Oppenheimer molecular dynamics is a promising tool for investigations of peptide-peptide ion interactions in the gas phase.

  12. GAS PHASE SELECTIVE PHOTOXIDATION OF ALCOHOLS USING LIGHT-ACTIVATED TITANIUM DIOXIDE AND MOLECULAR OXYGEN

    EPA Science Inventory

    Gas Phase Selective Oxidation of Alcohols Using Light-Activated Titanium Dioxide and Molecular Oxygen

    Gas phase selective oxidations of various primary and secondary alcohols are studied in an indigenously built stainless steel up-flow photochemical reactor using ultravi...

  13. The PDB is a covering set of small protein structures.

    PubMed

    Kihara, Daisuke; Skolnick, Jeffrey

    2003-12-01

    Structure comparisons of all representative proteins have been done. Employing the relative root mean square deviation (RMSD) from native enables the assessment of the statistical significance of structure alignments of different lengths in terms of a Z-score. Two conclusions emerge: first, proteins with their native fold can be distinguished by their Z-score. Second and somewhat surprising, all small proteins up to 100 residues in length have significant structure alignments to other proteins in a different secondary structure and fold class; i.e. 24.0% of them have 60% coverage by a template protein with a RMSD below 3.5A and 6.0% have 70% coverage. If the restriction that we align proteins only having different secondary structure types is removed, then in a representative benchmark set of proteins of 200 residues or smaller, 93% can be aligned to a single template structure (with average sequence identity of 9.8%), with a RMSD less than 4A, and 79% average coverage. In this sense, the current Protein Data Bank (PDB) is almost a covering set of small protein structures. The length of the aligned region (relative to the whole protein length) does not differ among the top hit proteins, indicating that protein structure space is highly dense. For larger proteins, non-related proteins can cover a significant portion of the structure. Moreover, these top hit proteins are aligned to different parts of the target protein, so that almost the entire molecule can be covered when combined. The number of proteins required to cover a target protein is very small, e.g. the top ten hit proteins can give 90% coverage below a RMSD of 3.5A for proteins up to 320 residues long. These results give a new view of the nature of protein structure space, and its implications for protein structure prediction are discussed.

  14. Quaternion maps of global protein structure.

    PubMed

    Hanson, Andrew J; Thakur, Sidharth

    2012-09-01

    The geometric structures of proteins are vital to the understanding of biochemical interactions. However, there is much yet to be understood about the spatial arrangements of the chains of amino acids making up any given protein. In particular, while conventional analysis tools like the Ramachandran plot supply some insight into the local relative orientation of pairs of amino acid residues, they provide little information about the global relative orientations of large groups of residues. We apply quaternion maps to families of coordinate frames defined naturally by amino acid residue structures as a way to expose global spatial relationships among residues within proteins. The resulting visualizations enable comparisons of absolute orientations as well as relative orientations, and thus generalize the framework of the Ramachandran plot. There are a variety of possible quaternion frames and visual representation strategies that can be chosen, and very complex quaternion maps can result. Just as Ramachandran plots are useful for addressing particular questions and not others, quaternion tools have characteristic domains of relevance. In particular, quaternion maps show great potential for answering specific questions about global residue alignment in crystallographic data and statistical orientation properties in Nuclear Magnetic Resonance (NMR) data that are very difficult to treat by other methods. PMID:23099777

  15. DAPS: Database of Aligned Protein Structures

    DOE Data Explorer

    Mallick, Parag; Rice, Danny; Eisenberg, David

    DAPS is based on the FSSP, DSSP, PDB and CATH databases. There also exists a subset of DAPS known as DDAPS (also pronounced DAPS) - Database of Distant Aligned Protein Structures. It is a database of structures that have low sequence similarity but share a similar fold. There are a number of filters used to make the DDAPS list more useful. The algorithm requires that an FSSP file exists for one of the members of a pair and that the other member is listed in that FSSP file. It requires that each member of the pair be within the CATH database and share a common CAT classification. It also requires that the secondary structure can be determined by DSSP. How is DAPS constructed? We begin with the set of all chains from the current release of the PDB. An all on all search is done on the list to find pairs that have the same fold acoording to both the FSSP and CATH databases and clustered into groups by a representative structure (representative structures have less than 25% sequence identity to each other). For each protein pair, regions aligned by the DALI program are extracted from the corresponding FSSP file, or recomputed using DALI-lite. In domain DAPS, only regions that are called "domains" by CATH are included in the alignment. The amino acid type, secondary structure type, and solvent accessibility are extracted from the DSSP file and written pairwise into the database. DAPS is updated with updates of CATH.[Taken from http://nihserver.mbi.ucla.edu/DAPS/daps_help.html

  16. Hot wire chemical vapor deposition chemistry in the gas phase and on the catalyst surface with organosilicon compounds.

    PubMed

    Shi, Yujun

    2015-02-17

    shown that ring-opening reactions play a vital role in characterizing the reaction chemistry. On the other hand, exocyclic Si-H(CH3) bond cleavages are more important in the less-puckered disilacyclobutane molecules. Metal filaments are essential in HWCVD since they serve as catalysts to decompose precursor gases to reactive species, which initiate gas-phase reaction chemistry and thin film growth. We discuss the structural changes in metal filaments when exposed to various precursor gases. Depending on the nature of the radical intermediates formed from the hot-wire decomposition and subsequent gas-phase reactions, metal silicides and carbides can be formed. Overall, study of the gas-phase reaction chemistry in HWCVD provides important knowledge of the chemical species produced prior to their deposition on a substrate surface. This helps in identifying the major contributor to alloy formation on the filament itself and the film growth, and consequently, in determining the properties of the deposited films. An integrated knowledge of the gas-phase reaction chemistry, filament alloy formation, and thin film deposition is required for an efficient deposition of high-quality thin films and nanomaterials. PMID:25586211

  17. Structure prediction of magnetosome-associated proteins.

    PubMed

    Nudelman, Hila; Zarivach, Raz

    2014-01-01

    Magnetotactic bacteria (MTB) are Gram-negative bacteria that can navigate along geomagnetic fields. This ability is a result of a unique intracellular organelle, the magnetosome. These organelles are composed of membrane-enclosed magnetite (Fe3O4) or greigite (Fe3S4) crystals ordered into chains along the cell. Magnetosome formation, assembly, and magnetic nano-crystal biomineralization are controlled by magnetosome-associated proteins (MAPs). Most MAP-encoding genes are located in a conserved genomic region - the magnetosome island (MAI). The MAI appears to be conserved in all MTB that were analyzed so far, although the MAI size and organization differs between species. It was shown that MAI deletion leads to a non-magnetic phenotype, further highlighting its important role in magnetosome formation. Today, about 28 proteins are known to be involved in magnetosome formation, but the structures and functions of most MAPs are unknown. To reveal the structure-function relationship of MAPs we used bioinformatics tools in order to build homology models as a way to understand their possible role in magnetosome formation. Here we present a predicted 3D structural models' overview for all known Magnetospirillum gryphiswaldense strain MSR-1 MAPs.

  18. Structural Characterization of Missense Mutations Using High Resolution Mass Spectrometry: A Case Study of the Parkinson's-Related Protein, DJ-1

    NASA Astrophysics Data System (ADS)

    Ben-Nissan, Gili; Chotiner, Almog; Tarnavsky, Mark; Sharon, Michal

    2016-06-01

    Missense mutations that lead to the expression of mutant proteins carrying single amino acid substitutions are the cause of numerous diseases. Unlike gene lesions, insertions, deletions, nonsense mutations, or modified RNA splicing, which affect the length of a polypeptide, or determine whether a polypeptide is translated at all, missense mutations exert more subtle effects on protein structure, which are often difficult to evaluate. Here, we took advantage of the spectral resolution afforded by the EMR Orbitrap platform, to generate a mass spectrometry-based approach relying on simultaneous measurements of the wild-type protein and the missense variants. This approach not only considerably shortens the analysis time due to the concurrent acquisition but, more importantly, enables direct comparisons between the wild-type protein and the variants, allowing identification of even subtle structural changes. We demonstrate our approach using the Parkinson's-associated protein, DJ-1. Together with the wild-type protein, we examined two missense mutants, DJ-1A104T and DJ-1D149A, which lead to early-onset familial Parkinson's disease. Gas-phase, thermal, and chemical stability assays indicate clear alterations in the conformational stability of the two mutants: the structural stability of DJ-1D149A is reduced, whereas that of DJ-1A104T is enhanced. Overall, we anticipate that the methodology presented here will be applicable to numerous other missense mutants, promoting the structural investigations of multiple variants of the same protein.

  19. GIS: a comprehensive source for protein structure similarities.

    PubMed

    Guerler, Aysam; Knapp, Ernst-Walter

    2010-07-01

    A web service for analysis of protein structures that are sequentially or non-sequentially similar was generated. Recently, the non-sequential structure alignment algorithm GANGSTA+ was introduced. GANGSTA+ can detect non-sequential structural analogs for proteins stated to possess novel folds. Since GANGSTA+ ignores the polypeptide chain connectivity of secondary structure elements (i.e. alpha-helices and beta-strands), it is able to detect structural similarities also between proteins whose sequences were reshuffled during evolution. GANGSTA+ was applied in an all-against-all comparison on the ASTRAL40 database (SCOP version 1.75), which consists of >10,000 protein domains yielding about 55 x 10(6) possible protein structure alignments. Here, we provide the resulting protein structure alignments as a public web-based service, named GANGSTA+ Internet Services (GIS). We also allow to browse the ASTRAL40 database of protein structures with GANGSTA+ relative to an externally given protein structure using different constraints to select specific results. GIS allows us to analyze protein structure families according to the SCOP classification scheme. Additionally, users can upload their own protein structures for pairwise protein structure comparison, alignment against all protein structures of the ASTRAL40 database (SCOP version 1.75) or symmetry analysis. GIS is publicly available at http://agknapp.chemie.fu-berlin.de/gplus.

  20. Dissociative electron attachment to the gas-phase nucleobase hypoxanthine

    NASA Astrophysics Data System (ADS)

    Dawley, M. Michele; Tanzer, Katrin; Carmichael, Ian; Denifl, Stephan; Ptasińska, Sylwia

    2015-06-01

    We present high-resolution measurements of the dissociative electron attachment (DEA) to isolated gas-phase hypoxanthine (C5H4N4O, Hyp), a tRNA purine base. The anion mass spectra and individual ion efficiency curves from Hyp were measured as a function of electron energy below 9 eV. The mass spectra at 1 and 6 eV exhibit the highest anion yields, indicating possible common precursor ions that decay into the detectable anionic fragments. The (Hyp - H) anion (C5H3N4O-) exhibits a sharp resonant peak at 1 eV, which we tentatively assign to a dipole-bound state of the keto-N1H,N9H tautomer in which dehydrogenation occurs at either the N1 or N9 position based upon our quantum chemical computations (B3LYP/6-311+G(d,p) and U(MP2-aug-cc-pVDZ+)) and prior studies with adenine. This closed-shell dehydrogenated anion is the dominant fragment formed upon electron attachment, as with other nucleobases. Seven other anions were also observed including (Hyp - NH)-, C4H3N4-/C4HN3O-, C4H2N3-, C3NO-/HC(HCN)CN-, OCN-, CN-, and O-. Most of these anions exhibit broad but weak resonances between 4 and 8 eV similar to many analogous anions from adenine. The DEA to Hyp involves significant fragmentation, which is relevant to understanding radiation damage of biomolecules.

  1. Gas-Phase Combustion Synthesis of Aluminum Nitride Powder

    NASA Technical Reports Server (NTRS)

    Axelbaum, R. L.; Lottes, C. R.; Huertas, J. I.; Rosen, L. J.

    1996-01-01

    Due to its combined properties of high electrical resistivity and high thermal conductivity aluminum nitride (AlN) is a highly desirable material for electronics applications. Methods are being sought for synthesis of unagglomerated, nanometer-sized powders of this material, prepared in such a way that they can be consolidated into solid compacts having minimal oxygen content. A procedure for synthesizing these powders through gas-phase combustion is described. This novel approach involves reacting AlCl3, NH3, and Na vapors. Equilibrium thermodynamic calculations show that 100% yields can be obtained for these reactants with the products being AlN, NaCl, and H2. The NaCl by-product is used to coat the AlN particles in situ. The coating allows for control of AlN agglomeration and protects the powders from hydrolysis during post-flame handling. On the basis of thermodynamic and kinetic considerations, two different approaches were employed to produce the powder, in co-flow diffusion flame configurations. In the first approach, the three reactants were supplied in separate streams. In the second, the AlCl3 and NH3 were premixed with HCl and then reacted with Na vapor. X-ray diffraction (XRD) spectra of as-produced powders show only NaCl for the first case and NaCl and AlN for the second. After annealing at 775 C tinder dynamic vacuum, the salt was removed and XRD spectra of powders from both approaches show only AlN. Aluminum metal was also produced in the co-flow flame by reacting AlCl3 with Na. XRD spectra of as-produced powders show the products to be only NaCl and elemental aluminum.

  2. Gas-phase chemistry of technetium carbonyl complexes.

    PubMed

    Wang, Yang; Qin, Zhi; Fan, Fang-Li; Haba, Hiromitsu; Komori, Yukiko; Cao, Shi-Wei; Wu, Xiao-Lei; Tan, Cun-Min

    2015-05-28

    Gas-phase chemical behaviors of short-lived technetium carbonyl complexes were studied using a low temperature isothermal chromatograph (IC) coupled with a (252)Cf spontaneous fission (SF) source. Fission products recoiled from the (252)Cf SF source were thermalized in a mixed gas containing CO, and then technetium carbonyl complexes were formed from reactions between CO gas and various technetium isotopes. A gas-jet system was employed to transport the volatile carbonyl complexes from a recoil chamber to the IC. Short IC columns made of Fluorinated Ethylene Propylene (FEP) Teflon and quartz were used to obtain chemical information about the technetium carbonyl complexes. The results for the (104)Tc-(106)Tc carbonyl complexes were found to be strongly influenced by the precursors, and showed the chemical behaviors of (104)Mo-(106)Mo carbonyl complexes, respectively. However, (107)Tc and (108)Tc could represent the chemical information of the element technetium due to their high independent yields and the very short half-lives of their precursors (107)Mo and (108)Mo. An adsorption enthalpy of about ΔHads = -43 kJ mol(-1) was determined for the Tc carbonyl complexes on both the Teflon and quartz surfaces by fitting the breakthrough curves of the (107)Tc and (108)Tc carbonyl complexes with a Monte Carlo simulation program. Chemical yields of around 25% were measured for the Tc carbonyl complexes relative to the transport yields obtained with the gas-jet transport of KCl aerosol particles with Ar carrier gas. Furthermore, the influence of a small amount of O2 gas on the yields of the Mo and Tc carbonyl complexes was studied.

  3. Uptake of Organic Gas Phase Species by 1-Methylnaphthalene

    NASA Astrophysics Data System (ADS)

    Zhang, H.; Xia, J.; Davidovits, P.; Jayne, J. T.; Kolb, C. E.; Worsnop, D. R.

    2002-12-01

    Using a droplet train apparatus, the mass accommodation coefficients (α) on 1-methylnapthalene of gas phase m-xylene, ethylbenzene, butylbenzene, α-pinene, γ-terpinene, and 2-methyl-2-hexanol were measured as a function of temperature (265 K to 296 K). 1-methylnapthalene was selected as a surrogate for hydrophobic and aromatic hydrocarbons found in tropospheric aerosols. The mass accommodation coefficients (α) of all the molecules obtained from these measurements exhibit negative temperature dependence. The upper and lower values of α at 265 K and 296 K respectively are: for m-xylene 0.44 and 0.26; for ethylbenzene 0.37 and 0.22; for butylbenzene 0.47 and 0.31; for α-pinene 0.47 and 0.096; for γ-terpinene 0.39 and 0.12; for 2-methyl-2-hexanol 0.44 and 0.26. The uptake measurements also yielded values for the product HDl1/2 for most of the molecules studied (H = Henry's law constant, Dl = liquid phase diffusion coefficient). Using calculated values of Dl the Henry's law constant is obtained, and expressed in the form ln H (M/atm) = -A + B/T. The A and B values for the molecules studied are listed in Table 1. Table 1: A and B values for the Henry's law constant H expressed as ln H (M/atm) = -A + B/T \\ m-xylene: A=7.20, B=4060\\ethylbenzene: A=5.81, B=3660\\butylbenzene: A=16.95, B=7330α-pinene: A=15.69, B=6360\\2-methyl-2-hexanol: A=9.95, B=4760

  4. IV-VI semiconductor lasers for gas phase biomarker detection

    NASA Astrophysics Data System (ADS)

    McCann, Patrick; Namjou, Khosrow; Roller, Chad; McMillen, Gina; Kamat, Pratyuma

    2007-09-01

    A promising absorption spectroscopy application for mid-IR lasers is exhaled breath analysis where sensitive, selective, and speedy measurement of small gas phase biomarker molecules can be used to diagnose disease and monitor therapies. Many molecules such as nitric oxide, ethane, formaldehyde, acetaldehyde, acetone, carbonyl sulfide, and carbon disulfide have been connected to diseases or conditions such as asthma, oxidative stress, breast cancer, lung cancer, diabetes, organ transplant rejection, and schizophrenia. Measuring these and other, yet to be discovered, biomarker molecules in exhaled breath with mid-IR lasers offers great potential for improving health care since such tests are non-invasive, real-time, and do not require expensive consumables or chemical reagents. Motivated by these potential benefits, mid-IR laser spectrometers equipped with presently available cryogenically-cooled IV-VI lasers mounted in compact Stirling coolers have been developed for clinical research applications. This paper will begin with a description of the development of mid-IR laser instruments and their use in the largest known exhaled breath clinical study ever performed. It will then shift to a description of recent work on the development of new IV-VI semiconductor quantum well materials and laser fabrication methods that offer the promise of low power consumption (i.e. efficient) continuous wave emission at room temperature. Taken together, the demonstration of compelling clinical applications with large market opportunities and the clear identification of a viable pathway to develop low cost mid-IR laser instrumentation can create a renewed focus for future research and development efforts within the mid-IR materials and devices area.

  5. Infrared spectroscopy of ionized corannulene in the gas phase

    NASA Astrophysics Data System (ADS)

    Galué, Héctor Alvaro; Rice, Corey A.; Steill, Jeffrey D.; Oomens, Jos

    2011-02-01

    The gas-phase infrared spectra of radical cationic and protonated corannulene were recorded by infrared multiple-photon dissociation (IRMPD) spectroscopy using the IR free electron laser for infrared experiments. Electrospray ionization was used to generate protonated corannulene and an IRMPD spectrum was recorded in a Fourier-transform ion cyclotron resonance mass spectrometer monitoring H-loss as a function of IR frequency. The radical cation was produced by 193-nm UV photoionization of the vapor of corannulene in a 3D quadrupole trap and IR irradiation produces H, H2, and C2Hx losses. Summing the spectral response of the three fragmentation channels yields the IRMPD spectrum of the radical cation. The spectra were analyzed with the aid of quantum-chemical calculations carried out at various levels of theory. The good agreement of theoretical and experimental spectra for protonated corannulene indicates that protonation occurs on one of the peripheral C-atoms, forming an sp3 hybridized carbon. The spectrum of the radical cation was examined taking into account distortions of the C5v geometry induced by the Jahn-Teller effect as a consequence of the degenerate 2E1 ground electronic state. As indicated by the calculations, the five equivalent Cs minima are separated by marginal barriers, giving rise to a dynamically distorted system. Although in general the character of the various computed vibrational bands appears to be in order, only a qualitative match to the experimental spectrum is found. Along with a general redshift of the calculated frequencies, the IR intensities of modes in the 1000-1250 cm-1 region show the largest discrepancy with the harmonic predictions. In addition to CH "in-plane" bending vibrations, these modes also exhibit substantial deformation of the pentagonal inner ring, which may relate directly to the vibronic interaction in the radical cation.

  6. Gas-phase chemistry of technetium carbonyl complexes.

    PubMed

    Wang, Yang; Qin, Zhi; Fan, Fang-Li; Haba, Hiromitsu; Komori, Yukiko; Cao, Shi-Wei; Wu, Xiao-Lei; Tan, Cun-Min

    2015-05-28

    Gas-phase chemical behaviors of short-lived technetium carbonyl complexes were studied using a low temperature isothermal chromatograph (IC) coupled with a (252)Cf spontaneous fission (SF) source. Fission products recoiled from the (252)Cf SF source were thermalized in a mixed gas containing CO, and then technetium carbonyl complexes were formed from reactions between CO gas and various technetium isotopes. A gas-jet system was employed to transport the volatile carbonyl complexes from a recoil chamber to the IC. Short IC columns made of Fluorinated Ethylene Propylene (FEP) Teflon and quartz were used to obtain chemical information about the technetium carbonyl complexes. The results for the (104)Tc-(106)Tc carbonyl complexes were found to be strongly influenced by the precursors, and showed the chemical behaviors of (104)Mo-(106)Mo carbonyl complexes, respectively. However, (107)Tc and (108)Tc could represent the chemical information of the element technetium due to their high independent yields and the very short half-lives of their precursors (107)Mo and (108)Mo. An adsorption enthalpy of about ΔHads = -43 kJ mol(-1) was determined for the Tc carbonyl complexes on both the Teflon and quartz surfaces by fitting the breakthrough curves of the (107)Tc and (108)Tc carbonyl complexes with a Monte Carlo simulation program. Chemical yields of around 25% were measured for the Tc carbonyl complexes relative to the transport yields obtained with the gas-jet transport of KCl aerosol particles with Ar carrier gas. Furthermore, the influence of a small amount of O2 gas on the yields of the Mo and Tc carbonyl complexes was studied. PMID:25920667

  7. Dissociative electron attachment to the gas-phase nucleobase hypoxanthine

    SciTech Connect

    Dawley, M. Michele; Tanzer, Katrin; Denifl, Stephan E-mail: Sylwia.Ptasinska.1@nd.edu; Carmichael, Ian; Ptasińska, Sylwia E-mail: Sylwia.Ptasinska.1@nd.edu

    2015-06-07

    We present high-resolution measurements of the dissociative electron attachment (DEA) to isolated gas-phase hypoxanthine (C{sub 5}H{sub 4}N{sub 4}O, Hyp), a tRNA purine base. The anion mass spectra and individual ion efficiency curves from Hyp were measured as a function of electron energy below 9 eV. The mass spectra at 1 and 6 eV exhibit the highest anion yields, indicating possible common precursor ions that decay into the detectable anionic fragments. The (Hyp − H) anion (C{sub 5}H{sub 3}N{sub 4}O{sup −}) exhibits a sharp resonant peak at 1 eV, which we tentatively assign to a dipole-bound state of the keto-N1H,N9H tautomer in which dehydrogenation occurs at either the N1 or N9 position based upon our quantum chemical computations (B3LYP/6-311+G(d,p) and U(MP2-aug-cc-pVDZ+)) and prior studies with adenine. This closed-shell dehydrogenated anion is the dominant fragment formed upon electron attachment, as with other nucleobases. Seven other anions were also observed including (Hyp − NH){sup −}, C{sub 4}H{sub 3}N{sub 4}{sup −}/C{sub 4}HN{sub 3}O{sup −}, C{sub 4}H{sub 2}N{sub 3}{sup −}, C{sub 3}NO{sup −}/HC(HCN)CN{sup −}, OCN{sup −}, CN{sup −}, and O{sup −}. Most of these anions exhibit broad but weak resonances between 4 and 8 eV similar to many analogous anions from adenine. The DEA to Hyp involves significant fragmentation, which is relevant to understanding radiation damage of biomolecules.

  8. Measurement of Gas-phase Acids in Diesel Exhaust

    NASA Astrophysics Data System (ADS)

    Wentzell, J. J.; Liggio, J.; Li, S.; Vlasenko, A. L.; Staebler, R. M.; Brook, J.; Lu, G.; Poitras, M.; Chan, T.

    2012-12-01

    Gas-phase acids were measured using chemical ionization mass spectrometry (CIMS) as part of the Diesel Engine Emission Research Experiment (DEERE). The CIMS technique, utilizing acetate ion (CH3COO-) as a reagent ion, proved to be a rapid (measurements on the order of seconds) and sensitive (several counts/pptv) method of quantifying the acid emissions. Diluted diesel exhaust measurements were made from a Constant Volume Sampling dilution tunnel using a light duty (1.9L turbocharged Volkswagen Jetta TDI) diesel engine equipped with an OEM diesel oxidation catalyst and exhaust gas recirculation, mounted on an engine dynamometer. Acids measured included isocyanic, nitrous, nitric, propionic and sum of lactic and oxalic, as well as other unidentified compounds. Complimentary measurements of CO, CO2, Total Hydrocarbon (THC), and NOx, were also performed. Several engine modes (different engine rpm and torque outputs) at steady state were examined to determine their effect on acid emissions. Emission rates with respect to NOx and fuel based emission factors were determined. Measurements of HONO fuel emission factors agree well with real-world measurements within a traffic tunnel.1 The first estimate of isocyanic acid emission factors from a diesel engine is reported, and suggests that the emission of this highly toxic compound in diesel exhaust should not be ignored. 1. Kurtenbach, R., Becker, K. H., Gomes, J. A. G., Kleffmann, J.,Lorzer, J. C., Spittler, M., Wiesen, P., Ackermann, R., Geyer, A.,and Platt, U.: Investigations of emissions and heterogeneous formation of HONO in a road traffic tunnel, Atmos. Environ., 35, 3385-3394, doi:10.1016/S1352-2310(01)00138-8, 2001.

  9. CHAOS III: Gas-phase Abundances in NGC 5457

    NASA Astrophysics Data System (ADS)

    Croxall, Kevin V.; Pogge, Richard W.; Berg, Danielle A.; Skillman, Evan D.; Moustakas, John

    2016-10-01

    We present Large Binocular Telescope observations of 109 H ii regions in NGC 5457 (M101) obtained with the Multi-Object Double Spectrograph. We have robust measurements of one or more temperature-sensitive auroral emission lines for 74 H ii regions, permitting the measurement of “direct” gas-phase abundances. Comparing the temperatures derived from the different ionic species, we find: (1) strong correlations of T[N ii] with T[S iii] and T[O iii], consistent with little or no intrinsic scatter; (2) a correlation of T[S iii] with T[O iii], but with significant intrinsic dispersion; (3) overall agreement between T[N ii], T[S ii], and T[O ii], as expected, but with significant outliers; (4) the correlations of T[N ii] with T[S iii] and T[O iii] match the predictions of photoionization modeling while the correlation of T[S iii] with T[O iii] is offset from the prediction of photoionization modeling. Based on these observations, which include significantly more observations of lower excitation H ii regions, missing in many analyses, we inspect the commonly used ionization correction factors (ICFs) for unobserved ionic species and propose new empirical ICFs for S and Ar. We have discovered an unexpected population of H ii regions with a significant offset to low values in Ne/O, which defies explanation. We derive radial gradients in O/H and N/O which agree with previous studies. Our large observational database allows us to examine the dispersion in abundances, and we find intrinsic dispersions of 0.074 ± 0.009 in O/H and 0.095 ± 0.009 in N/O (at a given radius). We stress that this measurement of the intrinsic dispersion comes exclusively from direct abundance measurements of H ii regions in NGC 5457.

  10. Gas-Phase Combustion Synthesis of Nonoxide Nanoparticles in Microgravity

    NASA Technical Reports Server (NTRS)

    Axelbaum, R. L.; Kumfer, B. M.; Sun, Z.; Chao, B. H.

    2001-01-01

    Gas-phase combustion synthesis is a promising process for creating nanoparticles for the growing nanostructure materials industry. The challenges that must be addressed are controlling particle size, preventing hard agglomerates, maintaining purity, and, if nonoxides are synthesized, protecting the particles from oxidation and/or hydrolysis during post-processing. Sodium-halide Flame Encapsulation (SFE) is a unique methodology for producing nonoxide nanoparticles that addresses these challenges. This flame synthesis process incorporates sodium and metal-halide chemistry, resulting in nanoparticles that are encapsulated in salt during the early stages of their growth in the flame. Salt encapsulation has been shown to allow control of particle size and morphology, while serving as an effective protective coating for preserving the purity of the core particles. Metals and compounds that have been produced using this technology include Al, W, Ti, TiB2, AlN, and composites of W-Ti and Al-AlN. Oxygen content in SFE synthesized nano- AlN has been measured by neutron activation analysis to be as low as 0.54wt.%, as compared to over 5wt.% for unprotected AlN of comparable size. The overall objective of this work is to study the SFE process and nano-encapsulation so that they can be used to produce novel and superior materials. SFE experiments in microgravity allow the study of flame and particle dynamics without the influence of buoyancy forces. Spherical sodium-halide flames are produced in microgravity by ejecting the halide from a spherical porous burner into a quiescent atmosphere of sodium vapor and argon. Experiments are performed in the 2.2 sec Drop Tower at the NASA-Glenn Research Center. Numerical models of the flame and particle dynamics were developed and are compared with the experimental results.

  11. Gas Phase Thz Spectroscopy of Organosulfide and Organophosphorous Compounds Using a Synchrotron Source

    NASA Astrophysics Data System (ADS)

    Cuisset, Arnaud; Smirnova, Irina; Bocquet, Robin; Hindle, Francis; Mouret, Gael; Sadovskii, Dmitrii A.; Pirali, Olivier; Roy, Pascale

    2011-06-01

    This study concerns the gas phase rovibrational spectroscopy of organosulfide and organophosphorous which are considered as non toxic model compounds in the analysis of chemical weapon materials, high pathogenic and mutagenic agents, and other environmentally interesting air-borne species. The coupling of the synchrotron radiation with multipass cells and the FTIR spectrometer allowed to obtain very conclusive results in term of sensitivity and resolution and improved the previous results obtained with classical sources. For DMSO, using an optical path of 150 m the spectra have been recorded at the ultimate resolution of 0.001 Cm-1 allowing to fully resolve the rotational structure of the lowest vibrational modes observed in the THz region. In the 290 - 420 Cm-1 region, the rovibrational spectrum of the "perpendicular" and "parallel" vibrational bands associated with, respectively, the asymmetric ν23 and symmetric ν11 bending modes of DMSO have been recorded with a resolution of 1.5× 10-3 Cm-1. The gas phase vibrational spectra of organophosphorous compounds were measured by FTIR spectroscopy using the vapor pressure of the compounds. Except for TBP, the room temperature vapor pressure was sufficient to detect all active vibrational modes from THz to NIR domain. Contrary to DMSO, the rotational patterns of alkyl phosphates and alkyl phosphonates could not be resolved; only a vibrational analysis may be performed. Nevertheless, the spectral fingerprints observed in the THz region allowed a clear discrimination between the molecules and between the different molecular conformations. A. Cuisset, G. Mouret, O. Pirali, P. Roy, F. Cazier, H. Nouali, J. Demaison, J. Phys. Chem. B, 2008, 112:, 12516-12525 A. Cuisset, L. Nanobashvili, I. Smirnova, R. Bocquet, F. Hindle, G. Mouret, O. Pirali, P. Roy and D. A. Sadovskií, Chem. Phys. Lett., 2010, 492: 30-34 I. Smirnova, A. Cuisset, R. Bocquet, F. Hindle, G. Mouret, O. Pirali, P. Roy, J. Phys. Chem. B, 2010, 114: 16936-16947.

  12. Gas-phase H2O and CO2 towards massive protostars

    NASA Astrophysics Data System (ADS)

    Boonman, A. M. S.; van Dishoeck, E. F.; Lahuis, F.; Wright, C. M.; Doty, S. D.

    2000-11-01

    We present a study of gas-phase H2O and CO2 towards a sample of 14 massive protostars with the ISO-SWS. Modeling of the H2O spectra using a homogeneous model with a constant excitation temperature Tex shows that the H2O abundances increase with temperature, up to a few times 10-5 with respect to H2 for the hottest sources (Tex~ 500 K). This is still a factor of 10 lower than the H2O ice abundances observed towards cold sources in which evaporation is not significant (Keane et al. 2000). Gas-phase CO2 is not abundant in our sources. The abundances are nearly constant for Tex >~ 100 K at a value of a few times 10-7, much lower than the solid-state abundances of ~1-3× 10-6 (Gerakines et al. 1999). Gas/solid ratios have been determined, using the solid-state features of H2O (Keane et al. 2000) and CO2 (Gerakines et al. 1999) as observed with ISO-SWS towards the same objects. For both H2O and CO2 the gas/solid ratio increases with temperature, but the increase is much stronger for H2O than for CO2, suggesting a different type of chemistry. In addition to the homogeneous models, a power law model has been developed for one of our sources, based on the physical structure of this region as determined from submillimeter data by van der Tak et al. (1999). The resulting H2O model spectrum gives a good fit to the data.

  13. Germanium-silicon alloy and core-shell nanocrystals by gas phase synthesis.

    PubMed

    Mehringer, Christian; Kloner, Christian; Butz, Benjamin; Winter, Benjamin; Spiecker, Erdmann; Peukert, Wolfgang

    2015-03-12

    In this work we present a novel route to synthesize well defined germanium-silicon alloy (GexSi1-x) and core-shell nanocrystals (NCs) employing monosilane (SiH4) and monogermane (GeH4) as precursors in a continuously operated two-stage hot-wall aerosol reactor setup. The first hot-wall reactor stage (HWR I) is used to produce silicon (Si) seed particles from SiH4 pyrolysis in Argon (Ar). The resulting seeding aerosol is fed into the second reactor stage (HWR II) and a mixture of SiH4 and GeH4 is added. The ratio of the precursors in the feed, their partial pressures, the synthesis temperature in HWR II and the overall pressure are varied depending on the desired morphology and composition. Alloy particle production is achieved in the heterogeneous surface reaction regime, meaning that germanium (Ge) and Si are deposited on the seed surface simultaneously. The NCs can be synthesized with any desired composition, whilst maintaining a mean diameter around 30 nm with a geometric standard deviation (GSD) around 1.25. The absorption behavior and the related fundamental optical band gap energy in dependence on the alloy composition are exemplarily presented. They prove the possibility to tailor NC properties for electronical and opto-electronical applications. In the homogeneous gas phase reaction regime facetted Ge-Si core-shell structures are accessible. The Ge deposition on the seeds precedes the Si deposition due to different gas phase reaction kinetics of the precursors. The Si layer grows epitaxially on the Ge core and is around 5 nm thick. PMID:25700152

  14. Germanium-silicon alloy and core-shell nanocrystals by gas phase synthesis.

    PubMed

    Mehringer, Christian; Kloner, Christian; Butz, Benjamin; Winter, Benjamin; Spiecker, Erdmann; Peukert, Wolfgang

    2015-03-12

    In this work we present a novel route to synthesize well defined germanium-silicon alloy (GexSi1-x) and core-shell nanocrystals (NCs) employing monosilane (SiH4) and monogermane (GeH4) as precursors in a continuously operated two-stage hot-wall aerosol reactor setup. The first hot-wall reactor stage (HWR I) is used to produce silicon (Si) seed particles from SiH4 pyrolysis in Argon (Ar). The resulting seeding aerosol is fed into the second reactor stage (HWR II) and a mixture of SiH4 and GeH4 is added. The ratio of the precursors in the feed, their partial pressures, the synthesis temperature in HWR II and the overall pressure are varied depending on the desired morphology and composition. Alloy particle production is achieved in the heterogeneous surface reaction regime, meaning that germanium (Ge) and Si are deposited on the seed surface simultaneously. The NCs can be synthesized with any desired composition, whilst maintaining a mean diameter around 30 nm with a geometric standard deviation (GSD) around 1.25. The absorption behavior and the related fundamental optical band gap energy in dependence on the alloy composition are exemplarily presented. They prove the possibility to tailor NC properties for electronical and opto-electronical applications. In the homogeneous gas phase reaction regime facetted Ge-Si core-shell structures are accessible. The Ge deposition on the seeds precedes the Si deposition due to different gas phase reaction kinetics of the precursors. The Si layer grows epitaxially on the Ge core and is around 5 nm thick.

  15. Structure based alignment and clustering of proteins (STRALCP)

    DOEpatents

    Zemla, Adam T.; Zhou, Carol E.; Smith, Jason R.; Lam, Marisa W.

    2013-06-18

    Disclosed are computational methods of clustering a set of protein structures based on local and pair-wise global similarity values. Pair-wise local and global similarity values are generated based on pair-wise structural alignments for each protein in the set of protein structures. Initially, the protein structures are clustered based on pair-wise local similarity values. The protein structures are then clustered based on pair-wise global similarity values. For each given cluster both a representative structure and spans of conserved residues are identified. The representative protein structure is used to assign newly-solved protein structures to a group. The spans are used to characterize conservation and assign a "structural footprint" to the cluster.

  16. Structural investigation of protein kinase C inhibitors

    NASA Technical Reports Server (NTRS)

    Barak, D.; Shibata, M.; Rein, R.

    1991-01-01

    The phospholipid and Ca2+ dependent protein kinase (PKC) plays an essential role in a variety of cellular events. Inhibition of PKC was shown to arrest growth in tumor cell cultures making it a target for possible antitumor therapy. Calphostins are potent inhibitors of PKC with high affinity for the enzyme regulatory site. Structural characteristics of calphostins, which confer the inhibitory activity, are investigated by comparing their optimized structures with the existing models for PKC activation. The resulting model of inhibitory activity assumes interaction with two out of the three electrostatic interaction sites postulated for activators. The model shows two sites of hydrophobic interaction and enables the inhibitory activity of gossypol to be accounted for.

  17. NMR Studies of Protein Structure and Dynamics

    NASA Astrophysics Data System (ADS)

    Li, Xiang

    Available from UMI in association with The British Library. Requires signed TDF. This thesis describes applications of 2D homonuclear NMR techniques to the study of protein structure and dynamics in solution. The sequential assignments for the 3G-residue bovine Pancreatic Polypeptide (bPP) are reported. The secondary and tertiary structure of bPP in solution has been determined from experimental NMR data. bPP has a well defined C-terminal alpha-helix and a rather ordered conformation in the N-terminal region. The two segments are joined by a turn which is poorly defined. Both the N- and the C-terminus are highly disordered. The mean solution structure of bPP is remarkably similar to the crystal structure of avian Pancreatic Polypeptide (aPP). The average conformations of most side-chains from the alpha-helix of bPP in solution are closely similar to those of aPP in the crystalline state. A large number of side-chains of bPP, however, show significant conformational averaging in solution. The 89-residue kringle domain of urokinase from both human and recombinant sources has been investigated. Sequential assignments based primarily on the recombinant sample and the determination of secondary structure are presented. Two helices have been identified; one of these corresponds to that reported for t-PA kringle 2, but does not exist in other kringles with known structures. The second helix is thus far unique to the urokinase kringle. Three antiparallel beta-sheets and three tight turns have also been identified. The tertiary fold of the molecule conforms broadly to that found for other kringles. Three regions in the urokinase kringle exhibit high local mobility; one of these, the Pro56-Pro62 segment, forms part of the proposed binding site. The other two mobile regions are the N- and C-termini which are likely to form the interfaces between the kringle and the other two domains (EGF and protease) in urokinase. The differential dynamic behaviours of the kringle and

  18. Protein Structural Studies by Traveling Wave Ion Mobility Spectrometry: A Critical Look at Electrospray Sources and Calibration Issues.

    PubMed

    Sun, Yu; Vahidi, Siavash; Sowole, Modupeola A; Konermann, Lars

    2016-01-01

    The question whether electrosprayed protein ions retain solution-like conformations continues to be a matter of debate. One way to address this issue involves comparisons of collision cross sections (Ω) measured by ion mobility spectrometry (IMS) with Ω values calculated for candidate structures. Many investigations in this area employ traveling wave IMS (TWIMS). It is often implied that nanoESI is more conducive for the retention of solution structure than regular ESI. Focusing on ubiquitin, cytochrome c, myoglobin, and hemoglobin, we demonstrate that Ω values and collisional unfolding profiles are virtually indistinguishable under both conditions. These findings suggest that gas-phase structures and ion internal energies are independent of the type of electrospray source. We also note that TWIMS calibration can be challenging because differences in the extent of collisional activation relative to drift tube reference data may lead to ambiguous peak assignments. It is demonstrated that this problem can be circumvented by employing collisionally heated calibrant ions. Overall, our data are consistent with the view that exposure of native proteins to electrospray conditions can generate kinetically trapped ions that retain solution-like structures on the millisecond time scale of TWIMS experiments. ᅟ PMID:26369778

  19. Protein Structural Studies by Traveling Wave Ion Mobility Spectrometry: A Critical Look at Electrospray Sources and Calibration Issues

    NASA Astrophysics Data System (ADS)

    Sun, Yu; Vahidi, Siavash; Sowole, Modupeola A.; Konermann, Lars

    2016-01-01

    The question whether electrosprayed protein ions retain solution-like conformations continues to be a matter of debate. One way to address this issue involves comparisons of collision cross sections (Ω) measured by ion mobility spectrometry (IMS) with Ω values calculated for candidate structures. Many investigations in this area employ traveling wave IMS (TWIMS). It is often implied that nanoESI is more conducive for the retention of solution structure than regular ESI. Focusing on ubiquitin, cytochrome c, myoglobin, and hemoglobin, we demonstrate that Ω values and collisional unfolding profiles are virtually indistinguishable under both conditions. These findings suggest that gas-phase structures and ion internal energies are independent of the type of electrospray source. We also note that TWIMS calibration can be challenging because differences in the extent of collisional activation relative to drift tube reference data may lead to ambiguous peak assignments. It is demonstrated that this problem can be circumvented by employing collisionally heated calibrant ions. Overall, our data are consistent with the view that exposure of native proteins to electrospray conditions can generate kinetically trapped ions that retain solution-like structures on the millisecond time scale of TWIMS experiments.

  20. Protein flexibility in the light of structural alphabets

    PubMed Central

    Craveur, Pierrick; Joseph, Agnel P.; Esque, Jeremy; Narwani, Tarun J.; Noël, Floriane; Shinada, Nicolas; Goguet, Matthieu; Leonard, Sylvain; Poulain, Pierre; Bertrand, Olivier; Faure, Guilhem; Rebehmed, Joseph; Ghozlane, Amine; Swapna, Lakshmipuram S.; Bhaskara, Ramachandra M.; Barnoud, Jonathan; Téletchéa, Stéphane; Jallu, Vincent; Cerny, Jiri; Schneider, Bohdan; Etchebest, Catherine; Srinivasan, Narayanaswamy; Gelly, Jean-Christophe; de Brevern, Alexandre G.

    2015-01-01

    Protein structures are valuable tools to understand protein function. Nonetheless, proteins are often considered as rigid macromolecules while their structures exhibit specific flexibility, which is essential to complete their functions. Analyses of protein structures and dynamics are often performed with a simplified three-state description, i.e., the classical secondary structures. More precise and complete description of protein backbone conformation can be obtained using libraries of small protein fragments that are able to approximate every part of protein structures. These libraries, called structural alphabets (SAs), have been widely used in structure analysis field, from definition of ligand binding sites to superimposition of protein structures. SAs are also well suited to analyze the dynamics of protein structures. Here, we review innovative approaches that investigate protein flexibility based on SAs description. Coupled to various sources of experimental data (e.g., B-factor) and computational methodology (e.g., Molecular Dynamic simulation), SAs turn out to be powerful tools to analyze protein dynamics, e.g., to examine allosteric mechanisms in large set of structures in complexes, to identify order/disorder transition. SAs were also shown to be quite efficient to predict protein flexibility from amino-acid sequence. Finally, in this review, we exemplify the interest of SAs for studying flexibility with different cases of proteins implicated in pathologies and diseases. PMID:26075209

  1. Protein flexibility in the light of structural alphabets.

    PubMed

    Craveur, Pierrick; Joseph, Agnel P; Esque, Jeremy; Narwani, Tarun J; Noël, Floriane; Shinada, Nicolas; Goguet, Matthieu; Leonard, Sylvain; Poulain, Pierre; Bertrand, Olivier; Faure, Guilhem; Rebehmed, Joseph; Ghozlane, Amine; Swapna, Lakshmipuram S; Bhaskara, Ramachandra M; Barnoud, Jonathan; Téletchéa, Stéphane; Jallu, Vincent; Cerny, Jiri; Schneider, Bohdan; Etchebest, Catherine; Srinivasan, Narayanaswamy; Gelly, Jean-Christophe; de Brevern, Alexandre G

    2015-01-01

    Protein structures are valuable tools to understand protein function. Nonetheless, proteins are often considered as rigid macromolecules while their structures exhibit specific flexibility, which is essential to complete their functions. Analyses of protein structures and dynamics are often performed with a simplified three-state description, i.e., the classical secondary structures. More precise and complete description of protein backbone conformation can be obtained using libraries of small protein fragments that are able to approximate every part of protein structures. These libraries, called structural alphabets (SAs), have been widely used in structure analysis field, from definition of ligand binding sites to superimposition of protein structures. SAs are also well suited to analyze the dynamics of protein structures. Here, we review innovative approaches that investigate protein flexibility based on SAs description. Coupled to various sources of experimental data (e.g., B-factor) and computational methodology (e.g., Molecular Dynamic simulation), SAs turn out to be powerful tools to analyze protein dynamics, e.g., to examine allosteric mechanisms in large set of structures in complexes, to identify order/disorder transition. SAs were also shown to be quite efficient to predict protein flexibility from amino-acid sequence. Finally, in this review, we exemplify the interest of SAs for studying flexibility with different cases of proteins implicated in pathologies and diseases. PMID:26075209

  2. Post-expression strategies for structural investigations of membrane proteins.

    PubMed

    Columbus, Linda

    2015-06-01

    Currently, membrane proteins only comprise 1.5% of the protein data bank and, thus, still remain a challenge for structural biologists. Expression, stabilization in membrane mimics (e.g. detergent), heterogeneity (conformational and chemical), and crystallization in the presence of a membrane mimic are four major bottlenecks encountered. In response, several post-expression protein modifications have been utilized to facilitate structure determination of membrane proteins. This review highlights four approaches: limited proteolysis, deglycosylation, cysteine alkylation, and lysine methylation. Combined these approaches have facilitated the structure determination of more than 40 membrane proteins and, therefore, are a useful addition to the membrane protein structural biologist's toolkit.

  3. Novel protein folds and their nonsequential structural analogs

    PubMed Central

    Guerler, Aysam; Knapp, Ernst-Walter

    2008-01-01

    Newly determined protein structures are classified to belong to a new fold, if the structures are sufficiently dissimilar from all other so far known protein structures. To analyze structural similarities of proteins, structure alignment tools are used. We demonstrate that the usage of nonsequential structure alignment tools, which neglect the polypeptide chain connectivity, can yield structure alignments with significant similarities between proteins of known three-dimensional structure and newly determined protein structures that possess a new fold. The recently introduced protein structure alignment tool, GANGSTA, is specialized to perform nonsequential alignments with proper assignment of the secondary structure types by focusing on helices and strands only. In the new version, GANGSTA+, the underlying algorithms were completely redesigned, yielding enhanced quality of structure alignments, offering alignment against a larger database of protein structures, and being more efficient. We applied DaliLite, TM-align, and GANGSTA+ on three protein crystal structures considered to be novel folds. Applying GANGSTA+ to these novel folds, we find proteins in the ASTRAL40 database, which possess significant structural similarities, albeit the alignments are nonsequential and in some cases involve secondary structure elements aligned in reverse orientation. A web server is available at http://agknapp.chemie.fu-berlin.de/gplus for pairwise alignment, visualization, and database comparison. PMID:18583523

  4. Structure-based druggability assessment of the mammalian structural proteome with inclusion of light protein flexibility.

    PubMed

    Loving, Kathryn A; Lin, Andy; Cheng, Alan C

    2014-07-01

    Advances reported over the last few years and the increasing availability of protein crystal structure data have greatly improved structure-based druggability approaches. However, in practice, nearly all druggability estimation methods are applied to protein crystal structures as rigid proteins, with protein flexibility often not directly addressed. The inclusion of protein flexibility is important in correctly identifying the druggability of pockets that would be missed by methods based solely on the rigid crystal structure. These include cryptic pockets and flexible pockets often found at protein-protein interaction interfaces. Here, we apply an approach that uses protein modeling in concert with druggability estimation to account for light protein backbone movement and protein side-chain flexibility in protein binding sites. We assess the advantages and limitations of this approach on widely-used protein druggability sets. Applying the approach to all mammalian protein crystal structures in the PDB results in identification of 69 proteins with potential druggable cryptic pockets.

  5. Structural determination of intact proteins using mass spectrometry

    DOEpatents

    Kruppa, Gary; Schoeniger, Joseph S.; Young, Malin M.

    2008-05-06

    The present invention relates to novel methods of determining the sequence and structure of proteins. Specifically, the present invention allows for the analysis of intact proteins within a mass spectrometer. Therefore, preparatory separations need not be performed prior to introducing a protein sample into the mass spectrometer. Also disclosed herein are new instrumental developments for enhancing the signal from the desired modified proteins, methods for producing controlled protein fragments in the mass spectrometer, eliminating complex microseparations, and protein preparatory chemical steps necessary for cross-linking based protein structure determination.Additionally, the preferred method of the present invention involves the determination of protein structures utilizing a top-down analysis of protein structures to search for covalent modifications. In the preferred method, intact proteins are ionized and fragmented within the mass spectrometer.

  6. Importance of the gas phase role to the prediction of energetic material behavior: An experimental study

    SciTech Connect

    Ali, A.N.; Son, S.F.; Asay, B.W.; Sander, R.K.

    2005-03-15

    Various thermal (radiative, conductive, and convective) initiation experiments are performed to demonstrate the importance of the gas phase role in combustion modeling of energetic materials (EM). A previously published condensed phase model that includes a predicted critical irradiance above which ignition is not possible is compared to experimental laser ignition results for octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) and 2,4,6-trinitrotoluene (TNT). Experimental results conflict with the predicted critical irradiance concept. The failure of the model is believed to result from a misconception about the role of the gas phase in the ignition process of energetic materials. The model assumes that ignition occurs at the surface and that evolution of gases inhibits ignition. High speed video of laser ignition, oven cook-off and hot wire ignition experiments captures the ignition of HMX and TNT in the gas phase. A laser ignition gap test is performed to further evaluate the effect of gas phase laser absorption and gas phase disruption on the ignition process. Results indicate that gas phase absorption of the laser energy is probably not the primary factor governing the gas phase ignition observations. It is discovered that a critical gap between an HMX pellet and a salt window of 6 mm{+-}0.4 mm exists below which ignition by CO{sub 2} laser is not possible at the tested irradiances of 29 W/cm{sup 2} and 38 W/cm{sup 2} for HMX ignition. These observations demonstrate that a significant disruption of the gas phase, in certain scenarios, will inhibit ignition, independent of any condensed phase processes. These results underscore the importance of gas phase processes and illustrate that conditions can exist where simple condensed phase models are inadequate to accurately predict the behavior of energetic materials.

  7. Membrane protein structures without crystals, by single particle electron cryomicroscopy

    PubMed Central

    Vinothkumar, Kutti R

    2015-01-01

    It is an exciting period in membrane protein structural biology with a number of medically important protein structures determined at a rapid pace. However, two major hurdles still remain in the structural biology of membrane proteins. One is the inability to obtain large amounts of protein for crystallization and the other is the failure to get well-diffracting crystals. With single particle electron cryomicroscopy, both these problems can be overcome and high-resolution structures of membrane proteins and other labile protein complexes can be obtained with very little protein and without the need for crystals. In this review, I highlight recent advances in electron microscopy, detectors and software, which have allowed determination of medium to high-resolution structures of membrane proteins and complexes that have been difficult to study by other structural biological techniques. PMID:26435463

  8. Gas phase chemistry of bis(pentamethylcyclopentadienyl)samarium

    SciTech Connect

    Marcalo, J.; Matos, A.P. de; Evans, W.

    1996-01-09

    The gas phase chemistry of bis(pentamethylcyclopentadienyl)samarium, (C{sub 5}Me{sub 5}){sub 2}Sm, was studied by Fourier transform ion cyclotron resonance mass spectrometry (FTICR/MS). Positive electron impact (EI) spectra showed the formation of (C{sub 5}Me{sub 5}){sub 2} Sm{sup +}, (C{sub 5}Me{sub 5})Sm{sup +}, and Sm{sup +}. All three ions reacted with (C{sub 5}Me{sub 5}){sub 2}Sm by charge transfer, as verified by double-resonance techniques, and (C{sub 5}Me{sub 5})Sm{sup +} also formed the (C{sub 5}Me{sub 5}){sub 3}Sm{sub 2}{sup +} ion in a condensation reaction with neutral (C{sub 5}Me{sub 5}){sub 2}Sm. The laser desorption/ionization (LDI) spectra showed, in addition to (C{sub 5}Me{sub 5}){sub 2}Sm{sup +}, (C{sub 5}Me{sub 5})Sm{sup +}, and Sm{sup +}, the formation of (C{sub 5}Me{sub 4}H)Sm{sup +} and (C{sub 5}Me{sub 4}CH{sub 2})Sm{sup +}. The latter species most probably involves a tetramethylfulvenide ligand. Access to all of the ionic species cited here could also be obtained by reacting laser-desorbed Sm{sup +} ions with pentamethylcyclopentadiene, C{sub 5}Me{sub 5}H. (C{sub 5}Me{sub 4}CH{sub 2})Sm{sup +}, (C{sub 5}Me{sub 4}H)Sm{sup +}, and (C{sub 5}Me{sub 5})Sm{sup +} were formed as primary products, and the metallocene ion (C{sub 5}Me{sub 5}){sub 2}Sm{sup +} resulted from the rapid addition of C{sub 5}Me{sub 5}H to (C{sub 5}Me{sub 4}CH{sub 2})Sm{sup +}. 34 refs., 4 figs.

  9. Gas-phase lithium cation affinity of glycine.

    PubMed

    Bourcier, Sophie; Chiaa, Ru Xuan; Mimbong, Rosa Ngo Biboum; Bouchoux, Guy

    2015-01-01

    The gas-phase lithium cation binding thermochemistry of glycine has been determined theoretically by quantum chemical calculations at the G4 level and experimentally by the extended kinetic method using electrospray ionization quadrupole time-of-flight tandem mass spectrometry. The lithium cation affinity of glycine, ∆(Li)H°(298)(GLY), i.e. the∆(Li)H°(298) of the reaction GlyLi(+)→ Gly + Li(+)) given by the G4 method is equal to 241.4 kJ.mol(-1) if only the most stable conformer of glycine is considered or to 242.3 kJ.mol(-1) if the 298K equilibrium mixture of neutral conformers is included in the calculation. The ∆(Li)H°(298)(GLY) deduced from the extended kinetic method is obviously dependent on the choice of the Li(+) affinity scale, thus∆(Li)H°(298)(GLY) is equal to 228.7±0.9(2.0) kJ.mol(- 1) if anchored to the recently re-evaluated lithium cation affinity scale but shifted to 235.4±1.0 kJ.mol(-1) if G4 computed lithium cation affinities of the reference molecules is used. This difference of 6.3 kJ.mol(-1) may originate from a compression of the experimental lithium affinity scale in the high ∆(Li)H°(298) region. The entropy change associated with the reaction GlyLi(+)→Gly + Li(+) reveals a gain of approximately 15 J.mol(-) 1.K(-1) with respect to monodentate Li(+) acceptors. The origin of this excess entropy is attributed to the bidentate interaction between the Li(+) cation and both the carbonyl oxygen and the nitrogen atoms of glycine. The computed G4 Gibbs free energy,∆(Li)G°(298)(GLY) is equal to 205.3 kJ.mol(-1), a similar result, 201.0±3.4 kJ.mol(-1), is obtained from the experiment if the∆(Li)G°(298) of the reference molecules is anchored on the G4 results. PMID:26307695

  10. Gas-phase lithium cation affinity of glycine.

    PubMed

    Bourcier, Sophie; Chiaa, Ru Xuan; Mimbong, Rosa Ngo Biboum; Bouchoux, Guy

    2015-01-01

    The gas-phase lithium cation binding thermochemistry of glycine has been determined theoretically by quantum chemical calculations at the G4 level and experimentally by the extended kinetic method using electrospray ionization quadrupole time-of-flight tandem mass spectrometry. The lithium cation affinity of glycine, ∆(Li)H°(298)(GLY), i.e. the∆(Li)H°(298) of the reaction GlyLi(+)→ Gly + Li(+)) given by the G4 method is equal to 241.4 kJ.mol(-1) if only the most stable conformer of glycine is considered or to 242.3 kJ.mol(-1) if the 298K equilibrium mixture of neutral conformers is included in the calculation. The ∆(Li)H°(298)(GLY) deduced from the extended kinetic method is obviously dependent on the choice of the Li(+) affinity scale, thus∆(Li)H°(298)(GLY) is equal to 228.7±0.9(2.0) kJ.mol(- 1) if anchored to the recently re-evaluated lithium cation affinity scale but shifted to 235.4±1.0 kJ.mol(-1) if G4 computed lithium cation affinities of the reference molecules is used. This difference of 6.3 kJ.mol(-1) may originate from a compression of the experimental lithium affinity scale in the high ∆(Li)H°(298) region. The entropy change associated with the reaction GlyLi(+)→Gly + Li(+) reveals a gain of approximately 15 J.mol(-) 1.K(-1) with respect to monodentate Li(+) acceptors. The origin of this excess entropy is attributed to the bidentate interaction between the Li(+) cation and both the carbonyl oxygen and the nitrogen atoms of glycine. The computed G4 Gibbs free energy,∆(Li)G°(298)(GLY) is equal to 205.3 kJ.mol(-1), a similar result, 201.0±3.4 kJ.mol(-1), is obtained from the experiment if the∆(Li)G°(298) of the reference molecules is anchored on the G4 results.

  11. Detection methods for atoms and radicals in the gas phase

    NASA Astrophysics Data System (ADS)

    Hack, W.

    This report lists atoms and free radicals in the gas phase which are of interest for environmental and flame chemistry and have been detected directly. The detection methods which have been used are discussed with respect to their range of application, specificity and sensitivity. In table 1, detection methods for the five atoms of group IV (C, Si, Ge, Sn, Pb) and about 60 radicals containing at least one atom of group IV are summarized (CH, Cd, Cf, CC1, CBr, Cn, Cs, CSe, CH2, CD2, Chf, Cdf, CHC1, CHBr, CF2, CC12, CBr2, CFC1, CFBr, CH3, CD3, CF3, CH2F, CH2C1, CH2Br, CHF2, CHC12, CHBr2, Hco, Fco, CH30, CD30, CH2OH, CH3S, Nco, CH4N, CH302, CF302; C2, C2N, C2H, C20, C2HO, C2H3, C2F3, C2H5, C2HsO, C2H4OH, CH3CO, CD3CO, C2H3O, C2H502, CH3COO2, C2H4N, C2H6N, C3; Si, SiF, SiF2, SiO, SiC, Si2; Ge, GeC, GeO, GeF, GeF2, GeCl2, Sn, SnF, SnO, SnF2, Pb, PbF, PbF2, PbO, PbS). In table 2 detection methods for about 25 other atoms and 60 radicals are listed: (H, D, O, O2, Oh, Od, HO2, DO2, F, Ci, Br, I, Fo, Cio, BrO, Io, FO2, C1O2, Li, Na, K, Rb, Cs, N, N3, Nh, Nd, Nf, Nci, NBr, NH2, ND2, Nhd, Nhf, NF2, NC12, N2H3, No, NO2, NO3, Hno, Dno, P, Ph, Pd, Pf, Pci, PH2, PD2, PF2, Po, As, AsO, AsS, Sb, Bi, S, S2, Sh, Sd, Sf, SF2, So, Hso, Dso, Sn, Se, Te, Se2, SeH, SeD, SeF, SeO, SeS, SeN, TeH, TeO, Bh, BH2, Bo, Bn, B02, Cd, Hg, UF5). The tables also cite some recent kinetic applications of the various methods.

  12. The gas-phase thermal chemistry of tetralin and related model systems

    SciTech Connect

    Malandra, J.

    1993-05-01

    The thesis is divided into 5 papers: gas-phase thermal decomposition of tetralin; flash vacuum pyrolysis of 3-benzocycloheptenone and 1,3, 4,5-tetrahydro-2-benzothiepin-2,2-dioxide (model systems for gas-phase pyrolysis of tetralin); high-temperature gas-phase reactions of o-allylbenzyl radicals generated by flash vacuum pyrolysis of is(o-allylbenzyl) oxalate; flash vacuum pyrolysis of 1,4-diphenylbutane; and flash vacuum pyrolysis of o-allyltoluene, o-(3-butenyl)toluene and o-(pentenyl)toluene were also used.

  13. Mm/submm Study of Gas-Phase Photoproducts from Methanol Interstellar Ice Analogues

    NASA Astrophysics Data System (ADS)

    Mesko, AJ; Smith, Houston Hartwell; Milam, Stefanie N.; Widicus Weaver, Susanna L.

    2016-06-01

    Icy grain reactions have gained quite the popularity in the astrochemistry community to explain the formation of complex organic molecules. Through temperature programmed desorption and photolysis experiments we use rotational spectroscopy to measure the gas-phase products of icy grain reactions. Previous results include testing detection limits of the system by temperature programmed desorption of methanol and water ices, photochemistry of gas-phase methanol, and detection of photodesorbed water from a pure water ice surface. Current work that will be discussed focuses on the detection of gas-phase CO and other photoproducts from an ice surface.

  14. Correlation between computed gas-phase and experimentally determined solution-phase infrared spectra: models of the iron-iron hydrogenase enzyme active site.

    PubMed

    Tye, Jesse W; Darensbourg, Marcetta Y; Hall, Michael B

    2006-09-01

    Gas-phase density functional theory calculations (B3LYP, double zeta plus polarization basis sets) are used to predict the solution-phase infrared spectra for a series of CO- and CN-containing iron complexes. It is shown that simple linear scaling of the computed C--O and C--N stretching frequencies yields accurate predictions of the the experimentally determined nu(CO) and nu(CN) values for a variety of complexes of different charges and in solvents of varying polarity. As examples of the technique, the resulting correlation is used to assign structures to spectroscopically observed but structurally ambiguous species in two different systems. For the (mu-SCH2CH2CH2S)[Fe(CO)3]2 complex in tetrahydrofuran solution, our calculations show that the initial electrochemical reduction process leads to a simple one-electron reduced product with a structure very similar to the (mu-SCH2CH2CH2S)[Fe(CO)3]2 parent complex. For the iron-iron hydrogenase enzyme active site, our computations show that the absence or presence of a water molecule near the distal iron center (the iron center further from the [4Fe4S] cluster and protein backbone) has very little effect on the predicted infrared spectra.

  15. Protein folding, protein structure and the origin of life: Theoretical methods and solutions of dynamical problems

    NASA Technical Reports Server (NTRS)

    Weaver, D. L.

    1982-01-01

    Theoretical methods and solutions of the dynamics of protein folding, protein aggregation, protein structure, and the origin of life are discussed. The elements of a dynamic model representing the initial stages of protein folding are presented. The calculation and experimental determination of the model parameters are discussed. The use of computer simulation for modeling protein folding is considered.

  16. Sampling and determination of gas-phase hydrogen peroxide following removal of ozone by gas-phase reaction with nitric oxide

    SciTech Connect

    Tanner, R.L.; Markovits, G.Y.; Ferreri, E.M.; Kelly, T.J.

    1986-01-01

    A method for determination of hydrogen peroxide in the ambient atmosphere is described, using impinger or diffusion scrubber collection of hydrogen peroxide with aqueous-phase analysis by an enzyme-catalyzed fluorescence technique. Interference from ozone at ambient levels is removed by gas-phase titration with excess nitric oxide. The impinger and diffusion scrubber collection techniques are shown to give equivalent results for atmospheric gas-phase hydrogen peroxide with limits of detection of 0.1 ppbv for approximately 60-min and 10-min sampling times, respectively.

  17. Predicting the protein-protein interactions using primary structures with predicted protein surface

    PubMed Central

    2010-01-01

    Background Many biological functions involve various protein-protein interactions (PPIs). Elucidating such interactions is crucial for understanding general principles of cellular systems. Previous studies have shown the potential of predicting PPIs based on only sequence information. Compared to approaches that require other auxiliary information, these sequence-based approaches can be applied to a broader range of applications. Results This study presents a novel sequence-based method based on the assumption that protein-protein interactions are more related to amino acids at the surface than those at the core. The present method considers surface information and maintains the advantage of relying on only sequence data by including an accessible surface area (ASA) predictor recently proposed by the authors. This study also reports the experiments conducted to evaluate a) the performance of PPI prediction achieved by including the predicted surface and b) the quality of the predicted surface in comparison with the surface obtained from structures. The experimental results show that surface information helps to predict interacting protein pairs. Furthermore, the prediction performance achieved by using the surface estimated with the ASA predictor is close to that using the surface obtained from protein structures. Conclusion This work presents a sequence-based method that takes into account surface information for predicting PPIs. The proposed procedure of surface identification improves the prediction performance with an F-measure of 5.1%. The extracted surfaces are also valuable in other biomedical applications that require similar information. PMID:20122202

  18. Fold assessment for comparative protein structure modeling.

    PubMed

    Melo, Francisco; Sali, Andrej

    2007-11-01

    Accurate and automated assessment of both geometrical errors and incompleteness of comparative protein structure models is necessary for an adequate use of the models. Here, we describe a composite score for discriminating between models with the correct and incorrect fold. To find an accurate composite score, we designed and applied a genetic algorithm method that searched for a most informative subset of 21 input model features as well as their optimized nonlinear transformation into the composite score. The 21 input features included various statistical potential scores, stereochemistry quality descriptors, sequence alignment scores, geometrical descriptors, and measures of protein packing. The optimized composite score was found to depend on (1) a statistical potential z-score for residue accessibilities and distances, (2) model compactness, and (3) percentage sequence identity of the alignment used to build the model. The accuracy of the composite score was compared with the accuracy of assessment by single and combined features as well as by other commonly used assessment methods. The testing set was representative of models produced by automated comparative modeling on a genomic scale. The composite score performed better than any other tested score in terms of the maximum correct classification rate (i.e., 3.3% false positives and 2.5% false negatives) as well as the sensitivity and specificity across the whole range of thresholds. The composite score was implemented in our program MODELLER-8 and was used to assess models in the MODBASE database that contains comparative models for domains in approximately 1.3 million protein sequences.

  19. 3-Dimensional Protein Structure of Influenza

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The loss of productivity due to flu is staggering. Costs range as much as $20 billio a year. High mutation rates of the flu virus have hindered development of new drugs or vaccines. The secret lies in a small molecule which is attached to the host cell's surface. Each flu virus, no matter what strain, must remove this small molecule to escape the host cell to spread infection. Using data from space and earth grown crystals, researchers from the Center of Macromolecular Crystallography (CMC) are desining drugs to bind with this protein's active site. This lock and key fit reduces the spread of flu in the body by blocking its escape route. In collaboration with its corporate partner, the CMC has refined drug structure in preparation for clinical trials. Tested and approved relief is expected to reach drugstores by year 2004.

  20. Connectivity independent protein-structure alignment: a hierarchical approach

    PubMed Central

    Kolbeck, Bjoern; May, Patrick; Schmidt-Goenner, Tobias; Steinke, Thomas; Knapp, Ernst-Walter

    2006-01-01

    Background Protein-structure alignment is a fundamental tool to study protein function, evolution and model building. In the last decade several methods for structure alignment were introduced, but most of them ignore that structurally similar proteins can share the same spatial arrangement of secondary structure elements (SSE) but differ in the underlying polypeptide chain connectivity (non-sequential SSE connectivity). Results We perform protein-structure alignment using a two-level hierarchical approach implemented in the program GANGSTA. On the first level, pair contacts and relative orientations between SSEs (i.e. α-helices and β-strands) are maximized with a genetic algorithm (GA). On the second level residue pair contacts from the best SSE alignments are optimized. We have tested the method on visually optimized structure alignments of protein pairs (pairwise mode) and for database scans. For a given protein structure, our method is able to detect significant structural similarity of functionally important folds with non-sequential SSE connectivity. The performance for structure alignments with strictly sequential SSE connectivity is comparable to that of other structure alignment methods. Conclusion As demonstrated for several applications, GANGSTA finds meaningful protein-structure alignments independent of the SSE connectivity. GANGSTA is able to detect structural similarity of protein folds that are assigned to different superfamilies but nevertheless possess similar structures and perform related functions, even if these proteins differ in SSE connectivity. PMID:17118190

  1. Structural hot spots for the solubility of globular proteins

    PubMed Central

    Ganesan, Ashok; Siekierska, Aleksandra; Beerten, Jacinte; Brams, Marijke; Van Durme, Joost; De Baets, Greet; Van der Kant, Rob; Gallardo, Rodrigo; Ramakers, Meine; Langenberg, Tobias; Wilkinson, Hannah; De Smet, Frederik; Ulens, Chris; Rousseau, Frederic; Schymkowitz, Joost

    2016-01-01

    Natural selection shapes protein solubility to physiological requirements and recombinant applications that require higher protein concentrations are often problematic. This raises the question whether the solubility of natural protein sequences can be improved. We here show an anti-correlation between the number of aggregation prone regions (APRs) in a protein sequence and its solubility, suggesting that mutational suppression of APRs provides a simple strategy to increase protein solubility. We show that mutations at specific positions within a protein structure can act as APR suppressors without affecting protein stability. These hot spots for protein solubility are both structure and sequence dependent but can be computationally predicted. We demonstrate this by reducing the aggregation of human α-galactosidase and protective antigen of Bacillus anthracis through mutation. Our results indicate that many proteins possess hot spots allowing to adapt protein solubility independently of structure and function. PMID:26905391

  2. Ensemble-based evaluation for protein structure models

    PubMed Central

    Jamroz, Michal; Kolinski, Andrzej; Kihara, Daisuke

    2016-01-01

    Motivation: Comparing protein tertiary structures is a fundamental procedure in structural biology and protein bioinformatics. Structure comparison is important particularly for evaluating computational protein structure models. Most of the model structure evaluation methods perform rigid body superimposition of a structure model to its crystal structure and measure the difference of the corresponding residue or atom positions between them. However, these methods neglect intrinsic flexibility of proteins by treating the native structure as a rigid molecule. Because different parts of proteins have different levels of flexibility, for example, exposed loop regions are usually more flexible than the core region of a protein structure, disagreement of a model to the native needs to be evaluated differently depending on the flexibility of residues in a protein. Results: We propose a score named FlexScore for comparing protein structures that consider flexibility of each residue in the native state of proteins. Flexibility information may be extracted from experiments such as NMR or molecular dynamics simulation. FlexScore considers an ensemble of conformations of a protein described as a multivariate Gaussian distribution of atomic displacements and compares a query computational model with the ensemble. We compare FlexScore with other commonly used structure similarity scores over various examples. FlexScore agrees with experts’ intuitive assessment of computational models and provides information of practical usefulness of models. Availability and implementation: https://bitbucket.org/mjamroz/flexscore Contact: dkihara@purdue.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27307633

  3. The spectroscopy and dynamics of flexible biomolecules in the gas phase

    NASA Astrophysics Data System (ADS)

    Dian, Brian C.

    The work presented in the volume focuses on understanding the complex potential energy landscapes of flexible biomolecules in the gas phase. Through a variety of double and triple resonance spectroscopic techniques, the structure and dynamics of flexible biomolecules can be elucidated and information about the connectivity and barriers to isomerization can be revealed. This work is presented in three main sections. The first focuses on the conformational preferences of two dipeptide mimetics: n-acetyltryptophan amide and n-acetyltryptophan methyl amide. It is found that two main conformational structures exist: an extended backbone C5 structure and a contracted backbone that has an intramolecular hydrogen bond between the amide groups. The effects of the conformation on the electronic spectroscopy of the molecules is also studied. It is found that the conformation of the backbone in both molecules has a dramatic effect on the ordering of the excited electronic states: 1Lb, 1La and 1pisigma*. The second section focuses on the isomerization efficiency of melatonin in addition to the aforementioned species. Through the novel techniques of hole-filling spectroscopy and infrared induced population transfer spectroscopy isomerization quantum yields are determined. In the final section, hole-filling spectroscopy is used to study the vibrational cooling dynamics in a super-sonic expansion, and is coupled to stimulated-emission pumping as a means to probe the barriers to isomerization in the molecule tryptamine.

  4. Hydration of gas-phase ytterbium ion complexes studied by experiment and theory

    SciTech Connect

    Rutkowski, Philip X; Michelini, Maria C.; Bray, Travis H.; Russo, Nino; Marcalo, Joaquim; Gibson, John K.

    2011-02-11

    Hydration of ytterbium (III) halide/hydroxide ions produced by electrospray ionization was studied in a quadrupole ion trap mass spectrometer and by density functional theory (DFT). Gas-phase YbX{sub 2}{sup +} and YbX(OH){sup +} (X = OH, Cl, Br, or I) were found to coordinate from one to four water molecules, depending on the ion residence time in the trap. From the time dependence of the hydration steps, relative reaction rates were obtained. It was determined that the second hydration was faster than both the first and third hydrations, and the fourth hydration was the slowest; this ordering reflects a combination of insufficient degrees of freedom for cooling the hot monohydrate ion and decreasing binding energies with increasing hydration number. Hydration energetics and hydrate structures were computed using two approaches of DFT. The relativistic scalar ZORA approach was used with the PBE functional and all-electron TZ2P basis sets; the B3LYP functional was used with the Stuttgart relativistic small-core ANO/ECP basis sets. The parallel experimental and computational results illuminate fundamental aspects of hydration of f-element ion complexes. The experimental observations - kinetics and extent of hydration - are discussed in relationship to the computed structures and energetics of the hydrates. The absence of pentahydrates is in accord with the DFT results, which indicate that the lowest energy structures have the fifth water molecule in the second shell.

  5. Studying Gas-Phase Interconversion of Tautomers Using Differential Mobility Spectrometry

    NASA Astrophysics Data System (ADS)

    Campbell, J. Larry; Yang, Amy Meng-Ci; Melo, Luke R.; Hopkins, W. Scott

    2016-07-01

    In this study, we report on the use of differential mobility spectrometry (DMS) as a tool for studying tautomeric species, allowing a more in-depth interrogation of these elusive isomers using ion/molecule reactions and tandem mass spectrometry. As an example, we revisit a case study in which gas-phase hydrogen-deuterium exchange (HDX)—a probe of ion structure in mass spectrometry—actually altered analyte ion structure by tautomerization. For the N- and O-protonated tautomers of 4-aminobenzoic acid, when separated using DMS and subjected to subsequent HDX with trace levels of D2O, the anticipated difference between the exchange rates of the two tautomers is observed. However, when using higher levels of D2O or a more basic reagent, equivalent and almost complete exchange of all labile protons is observed. This second observation is a result of the interconversion of the N-protonated tautomer to the O-protonated form during HDX. We can monitor this transformation experimentally, with support from detailed molecular dynamics and electronic structure calculations. In fact, calculations suggest the onset of bulk solution phase properties for 4-aminobenzoic acid upon solvation with eight CH3OH molecules. These findings also underscore the need for choosing HDX reagents and conditions judiciously when separating interconvertible isomers using DMS.

  6. Reexamination of CO formation during formic acid decomposition on the Pt(1 1 1) surface in the gas phase

    NASA Astrophysics Data System (ADS)

    Wang, Yingying; Zhang, Dongju; Liu, Peng; Liu, Chengbu

    2016-08-01

    Existing theoretical results for formic acid (HCOOH) decomposition on Pt(1 1 1) cannot rationalize the easy CO poisoning of the catalysts in the gas phase. The present work reexamined HCOOH decomposition on Pt(1 1 1) by considering the effect of the initial adsorption structure of the reactant on the reactivity. Our calculations present a new adsorption configuration of HCOOH on Pt(1 1 1), from which the formation of CO is found to be competing with the formation of CO2. The newly proposed mechanism improves our understanding for the mechanism of HCOOH decomposition catalyzed by Pt-based catalysts.

  7. CASCADER: An M-chain gas-phase radionuclide transport and fate model. Volume 4 -- Users guide to CASCADR9

    SciTech Connect

    Cawlfield, D.E.; Emer, D.F.; Lindstrom, F.T.; Shott, G.J.

    1993-09-01

    Chemicals and radionuclides move either in the gas-phase, liquid-phase, or both phases in soils. They may be acted upon by either biological or abiotic processes through advection and/or dispersion. Additionally during the transport of parent and daughter radionuclides in soil, radionuclide decay may occur. This version of CASCADER called CASCADR9 starts with the concepts presented in volumes one and three of this series. For a proper understanding of how the model works, the reader should read volume one first. Also presented in this volume is a set of realistic scenarios for buried sources of radon gas, and the input and output file structure for CASCADER9.

  8. Spectroscopic Characterization and Reactivity of Triplet and Quintet Iron(IV) Oxo Complexes in the Gas Phase

    PubMed Central

    Andris, Erik; Jašík, Juraj; Gómez, Laura

    2016-01-01

    Abstract Closely structurally related triplet and quintet iron(IV) oxo complexes with a tetradentate aminopyridine ligand were generated in the gas phase, spectroscopically characterized, and their reactivities in hydrogen‐transfer and oxygen‐transfer reactions were compared. The spin states were unambiguously assigned based on helium tagging infrared photodissociation (IRPD) spectra of the mass‐selected iron complexes. It is shown that the stretching vibrations of the nitrate counterion can be used as a spectral marker of the central iron spin state. PMID:26878833

  9. The conformational flexibility of nucleic acid bases paired in gas phase: A Car-Parrinello molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Xiao, Shiyan; Liang, Haojun

    2012-05-01

    The flexibilities of pyrimidine and imidazole rings in the paired nucleobases are investigated using Car-Parrinello molecular dynamics simulation in gas phase. The pairing influence on the stiffness of rings is analyzed based on the molecular structure of the nucleobases and constraints caused by pairing. We prove that the flexibilities of pyrimidine rings in isolated state have subtle correlation with the degree of aromaticity of the rings. The pairings in nucleic base pairs cause the rings to be more rigid for G, T, and U but more flexible for A and the same for C.

  10. Evolution and physics in comparative protein structure modeling.

    PubMed

    Fiser, András; Feig, Michael; Brooks, Charles L; Sali, Andrej

    2002-06-01

    From a physical perspective, the native structure of a protein is a consequence of physical forces acting on the protein and solvent atoms during the folding process. From a biological perspective, the native structure of proteins is a result of evolution over millions of years. Correspondingly, there are two types of protein structure prediction methods, de novo prediction and comparative modeling. We review comparative protein structure modeling and discuss the incorporation of physical considerations into the modeling process. A good starting point for achieving this aim is provided by comparative modeling by satisfaction of spatial restraints. Incorporation of physical considerations is illustrated by an inclusion of solvation effects into the modeling of loops.

  11. Identification of gas-phase dimethyl sulfate and monomethyl hydrogen sulfate in the Los Angeles atmosphere

    SciTech Connect

    Eatough, D.J.; White, V.F.; Hansen, L.D.; Eatough, N.L.; Cheney, J.L.

    1986-09-01

    Gas-phase dimethyl sulfate and monomethyl hydrogen sulfate have been identified in the atmosphere in Los Angeles. Gas-phase concentrations of these two alkyl sulfates were determined by using analytical methods based on the collection of the compounds before collection of particles using diffusion denuders and after collection of particles using resin beds or sorption filters, and specific analysis of the collected alkyl sulfates by ion chromatography. The data show the dimethyl sulfate is present in both particles and the gas phase. The concentration of total gas-phase methyl sulfates was found to vary from 34 to 178 nmol/m/sup 3/ during the smog episode studied. These species constituted a significant fraction of the total sulfur budget in the Los Angeles basin during the sampling period.

  12. Identification of gas-phase dimethyl sulfate and monomethyl hydrogen sulfate in the Los Angeles atmosphere

    SciTech Connect

    Eatough, D.J.; White, V.F.; Hansen, L.D.; Eatough, N.L.; Cheney, J.L.

    1986-01-01

    Analytical techniques were developed for the collection and determination of gas-phase dimethyl sulfate and monomethyl sulfuric acid based on collection of the alkyl sulfate compounds with both denuder tubes and resin sorption beds and analysis of the collected material by ion chromatography. Gas-phase dimethyl sulfate and monomethyl sulfuric acid were identified in Los Angeles using these techniques. The data indicate that dimethyl sulfate is present in both particles and in the gas phase. The concentration of gas-phase methyl sulfates was found to be several micrograms/cu m. These species thus account for a significant fraction of the total sulfur budget in the Los Angeles Basin during the sample period.

  13. Gas-phase water-mediated equilibrium between methylglyoxal and its geminal diol.

    PubMed

    Axson, Jessica L; Takahashi, Kaito; De Haan, David O; Vaida, Veronica

    2010-04-13

    In aqueous solution, aldehydes, and to a lesser extent ketones, hydrate to form geminal diols. We investigate the hydration of methylglyoxal (MG) in the gas phase, a process not previously considered to occur in water-restricted environments. In this study, we spectroscopically identified methylglyoxal diol (MGD) and obtained the gas-phase partial pressures of MG and MGD. These results, in conjunction with the relative humidity, were used to obtain the equilibrium constant, K(P), for the water-mediated hydration of MG in the gas phase. The Gibbs free energy for this process, DeltaG(o), obtained as a result, suggests a larger than expected gas-phase diol concentration. This may have significant implications for understanding the role of organics in atmospheric chemistry.

  14. Chemical Nuclear Polarization of Biradicals Created by Photolysis of Cyclic Aliphatic Ketones in the Gas Phase

    NASA Astrophysics Data System (ADS)

    Obynochnyia, A. A.; Purtovb, P. A.; Salikhova, K. M.

    2008-02-01

    Chemical nuclear polarization (CNP) of short-lived biradicals created in the photolysis of cyclic ketones in the gas phase with a buffer gas of CDCl3 molecules was studied theoretically and experimentally. The magnetoresonance and kinetic parameters were proposed for the biradicals. The experimental fact that the CNP of cycloundecanone in the gas phase and liquid was the strongest was confirmed by calculations. The computational results agree well with the experiment for both gas and liquid phases.

  15. Gas-Phase Molecular Dynamics: High Resolution Spectroscopy and Collision Dynamics of Transient Species

    SciTech Connect

    Hall, G.E.

    2011-05-31

    This research is carried out as part of the Gas-Phase Molecular Dynamics program in the Chemistry Department at Brookhaven National Laboratory. Chemical intermediates in the elementary gas-phase reactions involved in combustion chemistry are investigated by high resolution spectroscopic tools. Production, reaction, and energy transfer processes are investigated by transient, double resonance, polarization and saturation spectroscopies, with an emphasis on technique development and connection with theory, as well as specific molecular properties.

  16. Gas-Phase Molecular Dynamics: High Resolution Spectroscopy and Collision Dynamics of Transient Species

    SciTech Connect

    Hall G. E.; Goncharov, V.

    2012-05-29

    This research is carried out as part of the Gas-Phase Molecular Dynamics program in the Chemistry Department at Brookhaven National Laboratory. Chemical intermediates in the elementary gas-phase reactions involved in combustion chemistry are investigated by high resolution spectroscopic tools. Production, reaction, and energy transfer processes are investigated by transient, double resonance, polarization and saturation spectroscopies, with an emphasis on technique development and connection with theory, as well as specific molecular properties.

  17. Ultrafast electronic relaxation of excited state vitamin B 12 in the gas phase

    NASA Astrophysics Data System (ADS)

    Shafizadeh, Niloufar; Poisson, Lionel; Soep, Benoıˆt

    2008-06-01

    The time evolution of electronically excited vitamin B 12 (cyanocobalamin) has been observed for the first time in the gas phase. It reveals an ultrafast decay to a state corresponding to metal excitation. This decay is interpreted as resulting from a ring to metal electron transfer. This opens the observation of the excited state of other complex biomimetic systems in the gas phase, the key to the characterisation of their complex evolution through excited electronic states.

  18. An atmospheric pressure flow reactor: Gas phase kinetics and mechanism in tropospheric conditions without wall effects

    NASA Technical Reports Server (NTRS)

    Koontz, Steven L.; Davis, Dennis D.; Hansen, Merrill

    1988-01-01

    A new type of gas phase flow reactor, designed to permit the study of gas phase reactions near 1 atm of pressure, is described. A general solution to the flow/diffusion/reaction equations describing reactor performance under pseudo-first-order kinetic conditions is presented along with a discussion of critical reactor parameters and reactor limitations. The results of numerical simulations of the reactions of ozone with monomethylhydrazine and hydrazine are discussed, and performance data from a prototype flow reactor are presented.

  19. Lead-enhanced gas-phase stability of multiply charged EDTA anions: a combined experimental and theoretical study.

    PubMed

    Liu, Chunxiao; Ouyang, Yongzhong; Jia, Bin; Zhu, Zhiqiang; Shi, Jianbo; Chen, Huanwen

    2012-06-01

    Besides their fundamental importance, multiply charged anions (MCAs) are considered as promising molecular capacitors for which their intrinsic stabilities are of great significance. Herein, the gas-phase stabilities of ethylenediaminetetraacetic acid (EDTA) anions (i.e. [EDTA-nH](n-), n = 1-4) and their Pb(II) complexes (i.e. [EDTA + Pb-nH]((2-n)-), n = 3, 4) have been investigated using an approach that combines extractive electrospray ionization mass spectrometry (EESI-MS) measurements, Car-Parrinello molecular dynamics simulations and density functional theory/Tao-Perdew-Staroverov-Scuseria calculations. The EESI-MS data showed that the doubly charged EDTA anions in the form of [EDTA-2H](2-) and [EDTA + Pb-4H](2-) were much more abundantly observed than the singly charged species such as [EDTA-H](-) and [EDTA + Pb-3H](-), respectively. The calculation results indicated that [EDTA-2H](2-) and [EDTA + Pb-4H](2-) anions were thermodynamically more stable than the [EDTA-H](-) and [EDTA + Pb-3H](-) species in the gas phase, respectively. The [EDTA + Pb-3H](-) anions preferred five-coordinated structure, whereas [EDTA + Pb-4H](2-) anions formed either five-coordinated or six-coordinated structures. The calculations further revealed that significant electron clouds drifting from the ligand EDTA to the metal Pb(II) ions and the large distances between the carboxylic groups reduced the Coulomb repulsion among the excess electrons of these MCAs. Our data demonstrated that EESI-MS combined with theoretic calculations were able to provide a deep insight into the fundamental behavior of stability of MCAs in the gas phase and, thus, might be useful tools for studying MCAs for potential molecular capacitors.

  20. Investigating Protein Structure and Evolution with SCOP2.

    PubMed

    Andreeva, Antonina; Howorth, Dave; Chothia, Cyrus; Kulesha, Eugene; Murzin, Alexey G

    2015-03-09

    SCOP2 is a successor to the Structural Classification of Proteins (SCOP) database that organizes proteins of known structure according to their structural and evolutionary relationships. It was designed to provide a more advanced framework for the classification of proteins. The SCOP2 classification is described in terms of a directed acyclic graph in which each node defines a relationship of particular type that is represented by a region of protein structure and sequence. The SCOP2 data are accessible via SCOP2-Browser and SCOP2-Graph. This protocol unit describes different ways to explore and investigate the SCOP2 evolutionary and structural groupings.

  1. Characterization and Prediction of Protein Flexibility Based on Structural Alphabets

    PubMed Central

    Liu, Bin

    2016-01-01

    Motivation. To assist efforts in determining and exploring the functional properties of proteins, it is desirable to characterize and predict protein flexibilities. Results. In this study, the conformational entropy is used as an indicator of the protein flexibility. We first explore whether the conformational change can capture the protein flexibility. The well-defined decoy structures are converted into one-dimensional series of letters from a structural alphabet. Four different structure alphabets, including the secondary structure in 3-class and 8-class, the PB structure alphabet (16-letter), and the DW structure alphabet (28-letter), are investigated. The conformational entropy is then calculated from the structure alphabet letters. Some of the proteins show high correlation between the conformation entropy and the protein flexibility. We then predict the protein flexibility from basic amino acid sequence. The local structures are predicted by the dual-layer model and the conformational entropy of the predicted class distribution is then calculated. The results show that the conformational entropy is a good indicator of the protein flexibility, but false positives remain a problem. The DW structure alphabet performs the best, which means that more subtle local structures can be captured by large number of structure alphabet letters. Overall this study provides a simple and efficient method for the characterization and prediction of the protein flexibility. PMID:27660756

  2. Characterization and Prediction of Protein Flexibility Based on Structural Alphabets

    PubMed Central

    Liu, Bin

    2016-01-01

    Motivation. To assist efforts in determining and exploring the functional properties of proteins, it is desirable to characterize and predict protein flexibilities. Results. In this study, the conformational entropy is used as an indicator of the protein flexibility. We first explore whether the conformational change can capture the protein flexibility. The well-defined decoy structures are converted into one-dimensional series of letters from a structural alphabet. Four different structure alphabets, including the secondary structure in 3-class and 8-class, the PB structure alphabet (16-letter), and the DW structure alphabet (28-letter), are investigated. The conformational entropy is then calculated from the structure alphabet letters. Some of the proteins show high correlation between the conformation entropy and the protein flexibility. We then predict the protein flexibility from basic amino acid sequence. The local structures are predicted by the dual-layer model and the conformational entropy of the predicted class distribution is then calculated. The results show that the conformational entropy is a good indicator of the protein flexibility, but false positives remain a problem. The DW structure alphabet performs the best, which means that more subtle local structures can be captured by large number of structure alphabet letters. Overall this study provides a simple and efficient method for the characterization and prediction of the protein flexibility.

  3. Gas-phase ions produced by freezing water or methanol for analysis using mass spectrometry.

    PubMed

    Pagnotti, Vincent S; Chakrabarty, Shubhashis; Wang, Beixi; Trimpin, Sarah; McEwen, Charles N

    2014-08-01

    Introducing water or methanol containing a low concentration of volatile or nonvolatile analyte into an inlet tube cooled with dry ice linking atmospheric pressure and the first vacuum stage of a mass spectrometer produces gas-phase ions even of small proteins that can be detected by mass spectrometry. Collision-induced dissociation experiments conducted in the first vacuum region of the mass spectrometer suggest analyte ions being protected by a solvent cage. The charges may be produced by processes similar to those proposed for charge separation under freezing conditions in thunderclouds. By this process, the surface of an ice pellet is charged positive and the interior negative so that removal of surface results in charge separation. A reversal of surface charge is expected for a heated droplet surface, and this is observed by heating rather than cooling the inlet tube. These observations are consistent with charged supercooled droplets or ice particles as intermediates in the production of analyte ions under freezing conditions. PMID:25014489

  4. Hydrothermal transformation of Chinese privet seed biomass to gas-phase and semi-volatile products.

    PubMed

    Eberhardt, Thomas L; Catallo, W James; Shupe, Todd F

    2010-06-01

    Hydrothermal (HT) treatment of seeds from Chinese privet (Ligustrum sinense), a non-native and invasive species in the southeastern United States, was examined with respect to the generation of gas-phase and semi-volatile organic chemicals of industrial importance from a lipid-rich biomass resource. Aqueous seed slurries were transformed into biphasic liquid systems comprised of a milky aqueous phase overlain by a black organic layer. Present in the headspace were elevated levels of CO(2) and acetic acid. Analysis of the semi-volatiles by GC-MS showed the formation of alkyl substituted benzenes, oxygenated cyclic alkenes, phenol, substituted phenolics, and alkyl substituted pyridines. Compared to immature seeds, mature seeds gave high relative amounts of oxygenated cyclic alkenes (cyclopentenones) and alkyl pyridines. The presence of fatty acids in the HT products likely resulted from both lipid hydrolysis reactions and the inherent stability of fatty acids under HT treatment conditions. Estimates of lignin and protein contents showed no definite trend that could be linked to the HT data. The proportion of aromatic HT products appeared to derive primarily from the proportion of extractives. Thus, variations in extractives yields impact HT product yields and thereby demonstrate the importance of timing in feedstock collection to favor targeted HT products. PMID:20149648

  5. Protein Structure, Function Set for Explosive Increase in Understanding.

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1986

    1986-01-01

    Cites advances in x-ray diffraction, nuclear magnetic resonance, computer modeling, and display to guide the design and analysis of protein structures. Reviews recent advances in knowledge, synthesis techniques, and theory of proteins. (JM)

  6. Systematic analysis of the use of amphipathic polymers for studies of outer membrane proteins using mass spectrometry

    PubMed Central

    Watkinson, Thomas G.; Calabrese, Antonio N.; Giusti, Fabrice; Zoonens, Manuela; Radford, Sheena E.; Ashcroft, Alison E.

    2015-01-01

    Membrane proteins (MPs) are essential for numerous important biological processes. Recently, mass spectrometry (MS), coupled with an array of related techniques, has been used to probe the structural properties of MPs and their complexes. Typically, detergent micelles have been employed for delivering MPs into the gas-phase, but these complexes have intrinsic properties that can limit the utility of structural studies of MPs using MS methods. Amphipols (APols) have advantages over detergent micelles and have been shown to be capable of delivering native MPs into the gas-phase. Comparing six different APols which vary in mass and charge, and the detergent n-dodecyl-β-d-maltopyranoside, we aimed to determine which APols are most efficient for delivery of native outer membrane proteins (OMPs) into the gas-phase. We show that maintaining the solution-phase folding and global structures of three different OMPs (PagP, OmpT and tOmpA) are independent of the APol used, but differences in OMP activity can result from the different APol:OMP complexes. ESI-IMS–MS analysis of OMP:APol complexes shows that the A8-35 APol is most proficient at liberating all three OMPs into the gas-phase, without altering their gas-phase conformations. PMID:26869850

  7. Prediction of three-dimensional transmembrane helical protein structures

    NASA Astrophysics Data System (ADS)

    Barth, Patrick

    Membrane proteins are critical to living cells and their dysfunction can lead to serious diseases. High-resolution structures of these proteins would provide very valuable information for designing eficient therapies but membrane protein crystallization is a major bottleneck. As an important alternative approach, methods for predicting membrane protein structures have been developed in recent years. This chapter focuses on the problem of modeling the structure of transmembrane helical proteins, and describes recent advancements, current limitations, and future challenges facing de novo modeling, modeling with experimental constraints, and high-resolution comparative modeling of these proteins. Abbreviations: MP, membrane protein; SP, water-soluble protein; RMSD, root-mean square deviation; Cα RMSD, root-mean square deviation over Cα atoms; TM, transmembrane; TMH, transmembrane helix; GPCR, G protein-coupled receptor; 3D, three dimensional; NMR, nuclear magnetic resonance spectroscopy; EPR, electron paramagnetic resonance spectroscopy; FTIR, Fourier transform infrared spectroscopy.

  8. Protein Production for Structural Genomics Using E. coli Expression

    PubMed Central

    Makowska-Grzyska, Magdalena; Kim, Youngchang; Maltseva, Natalia; Li, Hui; Zhou, Min; Joachimiak, Grazyna; Babnigg, Gyorgy; Joachimiak, Andrzej

    2014-01-01

    The goal of structural biology is to reveal details of the molecular structure of proteins in order to understand their function and mechanism. X-ray crystallography and NMR are the two best methods for atomic level structure determination. However, these methods require milligram quantities of proteins. In this chapter a reproducible methodology for large-scale protein production applicable to a diverse set of proteins is described. The approach is based on protein expression in E. coli as a fusion with a cleavable affinity tag that was tested on over 20,000 proteins. Specifically, a protocol for fermentation of large quantities of native proteins in disposable culture vessels is presented. A modified protocol that allows for the production of selenium-labeled proteins in defined media is also offered. Finally, a method for the purification of His6-tagged proteins on immobilized metal affinity chromatography columns that generates high-purity material is described in detail. PMID:24590711

  9. Layer-modulated synthesis of uniform tungsten disulfide nanosheet using gas-phase precursors

    NASA Astrophysics Data System (ADS)

    Park, Jusang; Lee, Wonseon; Choi, Taejin; Hwang, Sung-Hwan; Myoung, Jae Min; Jung, Jae-Hoon; Kim, Soo-Hyun; Kim, Hyungjun

    2015-01-01

    The synthesis of layered transition-metal-disulfide (MS2, M = Mo, W) nanosheets with layer controllability and large-area uniformity is an essential requirement for their application in electronic and optical devices. In this report, we describe a synthesis process of WS2 nanosheets with layer controllability and high uniformity using chemical vapor deposition (CVD) and WCl6 and H2S as gas-phase precursors. Through this process, we can systematically modulate the thickness of WS2 nanosheets by controlling the duration of the reaction between WCl6 and H2S. The CVD-grown WS2 nanosheets exhibit good stoichiometry as well as dependencies of a clear Raman shift and bandgap on the number of layers. These properties are confirmed by X-ray photoemission spectroscopy, Raman spectroscopy, and photoluminescence measurements. The number of layers of WS2 nanosheets is confirmed by atomic force microscopy. Finally, we demonstrate the fabrication and performance of a photodetector based on a hybrid structure consisting of graphene and a WS2 nanosheet.The synthesis of layered transition-metal-disulfide (MS2, M = Mo, W) nanosheets with layer controllability and large-area uniformity is an essential requirement for their application in electronic and optical devices. In this report, we describe a synthesis process of WS2 nanosheets with layer controllability and high uniformity using chemical vapor deposition (CVD) and WCl6 and H2S as gas-phase precursors. Through this process, we can systematically modulate the thickness of WS2 nanosheets by controlling the duration of the reaction between WCl6 and H2S. The CVD-grown WS2 nanosheets exhibit good stoichiometry as well as dependencies of a clear Raman shift and bandgap on the number of layers. These properties are confirmed by X-ray photoemission spectroscopy, Raman spectroscopy, and photoluminescence measurements. The number of layers of WS2 nanosheets is confirmed by atomic force microscopy. Finally, we demonstrate the fabrication

  10. Development and evaluation of the aerosol dynamics and gas phase chemistry model ADCHEM

    NASA Astrophysics Data System (ADS)

    Roldin, P.; Swietlicki, E.; Schurgers, G.; Arneth, A.; Lehtinen, K. E. J.; Boy, M.; Kulmala, M.

    2011-06-01

    The aim of this work was to develop a model suited for detailed studies of aerosol dynamics, gas and particle phase chemistry within urban plumes, from local scale (1 × 1 km2) to regional scale. This article describes and evaluates the trajectory model for Aerosol Dynamics, gas and particle phase CHEMistry and radiative transfer (ADCHEM). The model treats both vertical and horizontal dispersion perpendicular to an air mass trajectory (2-space dimensions). The Lagrangian approach enables a more detailed representation of the aerosol dynamics, gas and particle phase chemistry and a finer spatial and temporal resolution compared to that of available regional 3D-CTMs. These features make it among others well suited for urban plume studies. The aerosol dynamics model includes Brownian coagulation, dry deposition, wet deposition, in-cloud processing, condensation, evaporation, primary particle emissions and homogeneous nucleation. The organic mass partitioning was either modeled with a 2-dimensional volatility basis set (2D-VBS) or with the traditional two-product model approach. In ADCHEM these models consider the diffusion limited and particle size dependent condensation and evaporation of 110 and 40 different organic compounds respectively. The gas phase chemistry model calculates the gas phase concentrations of 61 different species, using 130 different chemical reactions. Daily isoprene and monoterpene emissions from European forests were simulated separately with the vegetation model LPJ-GUESS, and included as input to ADCHEM. ADCHEM was used to simulate the ageing of the urban plumes from the city of Malmö in southern Sweden (280 000 inhabitants). Several sensitivity tests were performed concerning the number of size bins, size structure method, aerosol dynamic processes, vertical and horizontal mixing, coupled or uncoupled condensation and the secondary organic aerosol formation. The simulations show that the full-stationary size structure gives accurate results

  11. Development and evaluation of the aerosol dynamic and gas phase chemistry model ADCHEM

    NASA Astrophysics Data System (ADS)

    Roldin, P.; Swietlicki, E.; Schurgers, G.; Arneth, A.; Lehtinen, K. E. J.; Boy, M.; Kulmala, M.

    2010-08-01

    The aim of this work was to develop a model ideally suited for detailed studies on aerosol dynamics, gas and particle phase chemistry within urban plumes, from local scale (1×1 km2) to regional or global scale. This article describes and evaluates the trajectory model for Aerosol Dynamics, gas and particle phase CHEMistry and radiative transfer (ADCHEM), which has been developed and used at Lund University since 2007. The model treats both vertical and horizontal dispersion perpendicular to an air mass trajectory (2-space dimensions), which is not treated in Lagrangian box-models (0-space dimensions). The Lagrangian approach enables a more detailed representation of the aerosol dynamics, gas and particle phase chemistry and a finer spatial and temporal resolution compared to that of available regional 3D-CTMs. These features make it among others ideally suited for urban plume studies. The aerosol dynamics model includes Brownian coagulation, dry deposition, wet deposition, in-cloud processing, condensation, evaporation, primary particle emissions and homogeneous nucleation. The gas phase chemistry model calculates the gas phase concentrations of 63 different species, using 119 different chemical reactions. Daily isoprene and monoterpene emissions from European forests were simulated separately with the vegetation model LPJ-GUESS, and included as input to ADCHEM. ADCHEM was used to simulate the ageing of the urban plumes from the city of Malmö in Southern Sweden (280 000 inhabitants). Several sensitivity tests were performed concerning the number of size bins, size structure method, coupled or uncoupled condensation, the volatility basis set (VBS) or traditional 2-product model for secondary organic aerosol formation, different aerosol dynamic processes and vertical and horizontal mixing. The simulations show that the full-stationary size structure gives accurate results with little numerical diffusion when more than 50 size bins are used between 1.5 and 2500 nm

  12. Separation mechanism of chiral impurities, ephedrine and pseudoephedrine, found in amphetamine-type substances using achiral modifiers in the gas phase.

    PubMed

    Holness, Howard K; Jamal, Adeel; Mebel, Alexander; Almirall, José R

    2012-11-01

    A new mechanism is proposed that describes the gas-phase separation of chiral molecules found in amphetamine-type substances (ATS) by the use of high-resolution ion mobility spectrometry (IMS). Straight-chain achiral alcohols of increasing carbon chain length, from methanol to n-octanol, are used as drift gas modifiers in IMS to highlight the mechanism proposed for gas-phase separations of these chiral molecules. The results suggest the possibility of using these achiral modifiers to separate the chiral molecules (R,S) and (S,R)-ephedrine and (S,S) and (R,R)-pseudoephedrine which contain an internal hydroxyl group at the first chiral center and an amino group at the other chiral center. Ionization was achieved with an electrospray source, the ions were introduced into an IMS with a resolving power of 80, and the resulting ion clusters were characterized with a coupled quadrupole mass spectrometer detector. A complementary computational study conducted at the density functional B3LYP/6-31g level of theory for the electronic structure of the analyte-modifier clusters was also performed, and showed either "bridged" or "independent" binding. The combined experimental and simulation data support the proposed mechanism for gas-phase chiral separations using achiral modifiers in the gas phase, thus enhancing the potential to conduct fast chiral separations with relative ease and efficiency.

  13. Internal symmetry in protein structures: prevalence, functional relevance and evolution.

    PubMed

    Balaji, Santhanam

    2015-06-01

    Symmetry has been found at various levels of biological organization in the protein structural universe. Numerous evolutionary studies have proposed connections between internal symmetry within protein tertiary structures, quaternary associations and protein functions. Recent computational methods, such as SymD and CE-Symm, facilitate a large-scale detection of internal symmetry in protein structures. Based on the results from these methods, about 20% of SCOP folds, superfamilies and families are estimated to have structures with internal symmetry (Figure 1d). All-β and membrane proteins fold classes contain a relatively high number of unique instances of internal symmetry. In addition to the axis of symmetry, anecdotal evidence suggests that, the region of connection or contact between symmetric units could coincide with functionally relevant sites within a fold. General principles that underlie protein internal symmetry and their connections to protein structural integrity and functions remain to be elucidated.

  14. Protein structure validation and analysis with X-ray crystallography.

    PubMed

    Papageorgiou, Anastassios C; Mattsson, Jesse

    2014-01-01

    X-ray crystallography is the main technique for the determination of protein structures. About 85 % of all protein structures known to date have been elucidated using X-ray crystallography. Knowledge of the three-dimensional structure of proteins can be used in various applications in biotechnology, biomedicine, drug design, and basic research and as a validation tool for protein modifications, ligand binding, and structural authenticity. Moreover, the requirement for pure, homogeneous, and stable protein solutions in crystallizations makes X-ray crystallography beneficial in other fields of protein research as well. Here, we describe the technique of X-ray protein crystallography and the steps involved for a successful three-dimensional crystal structure determination.

  15. Isomers and conformational barriers of gas phase nicotine, nornicotine and their protonated forms

    SciTech Connect

    Yoshida, Tomoki; Farone, William A.; Xantheas, Sotiris S.

    2014-07-17

    We report extensive conformational searches of the neutral nicotine, nornicotine and their protonated analogs that are based on ab-initio second order Møller-Plesset perturbation (MP2) electronic structure calculations. Initial searches were performed with the 6-31G(d,p) and the energetics of the most important structures were further refined from geometry optimizations with the aug-cc-pVTZ basis set. Based on the calculated free energies at T=298 K for the gas phase molecules, neutral nicotine has two dominant trans conformers, whereas neutral nornicotine is a mixture of several conformers. For nicotine, the protonation on both the pyridine and the pyrrolidine sites is energetically competitive, whereas nornicotine prefers protonation on the pyridine nitrogen. The protonated form of nicotine is mainly a mixture of two pyridine-protonated trans conformers and two pyrrolidine-protonated trans conformers, whereas the protonated form of nornicotine is a mixture of four pyridine-protonated trans conformers. Nornicotine is conformationally more flexible than nicotine, however it is less protonated at the biologically important pyrrolidine nitrogen site. The lowest energy isomers for each case were found to interconvert via low (< 6 kcal/mol) rotational barriers around the pyridine-pyrrolidine bond.

  16. NMR properties of hydrogen-bonded glycine cluster in gas phase

    NASA Astrophysics Data System (ADS)

    Carvalho, Jorge R.; da Silva, Arnaldo Machado; Ghosh, Angsula; Chaudhuri, Puspitapallab

    2016-11-01

    Density Functional Theory (DFT) calculations have been performed to study the effect of the hydrogen bond formation on the Nuclear Magnetic Resonance (NMR) parameters of hydrogen-bonded clusters of glycine molecules in gas-phase. DFT predicted isotropic chemical shifts of H, C, N and O of the isolated glycine with respect to standard reference materials are in reasonable agreement with available experimental data. The variations of isotropic and anisotropic chemical shifts for all atoms constituting these clusters containing up to four glycine molecules have been investigated systematically employing gradient corrected hybrid B3LYP functional with three different types of extended basis sets. The clusters are mainly stabilized by a network of strong hydrogen bonds among the carboxylic (COOH) groups of glycine monomers. The formation of hydrogen bond influences the molecular structure of the clusters significantly which, on the other hand, gets reflected in the variations of NMR properties. The carbon (C) atom of the sbnd COOH group, the bridging hydrogen (H) and the proton-donor oxygen (O) atom of the Osbnd H bond suffer downfield shift due to the formation of hydrogen bond. The hydrogen bond lengths and the structural complexity of the clusters are found to vary with the number of participating monomers. A direct correlation between the hydrogen bond length and isotropic chemical shift of the bridging hydrogen is observed in all cases. The individual variations of the principal axis elements in chemical shift tensor provide additional insight about the different nature of the monomers within the cluster.

  17. Theoretical study on the properties of linear and cyclic amides in gas phase and water solution.

    PubMed

    Aparicio-Martínez, S; Hall, K R; Balbuena, P B

    2006-07-27

    The structural and energetic properties of a group of selected amides, of well-known importance for the design of efficient clathrate inhibitors, are calculated with Hartree-Fock and density functional theory, B3LYP, theoretical levels, and a 6-311++g** basis set in the gas phase and a water solution. The conformational behavior of the molecules is studied through the scanning of the torsional potential energy surfaces and by the analysis of the differences in the energetic and structural properties between the isomers. The properties of the amides in water solution are determined within a self-consistent reaction field approach with a polarizable continuum model that allows the calculation of the different contributions to the free energy of solvation. The calculated barriers to rotation are in good agreement with the available experimental data and the comparison of the gas and water results shows the strong effect of the solute polarization. The properties of different amide-water complexes are calculated and compared with available experimental information.

  18. Resonant x-ray emission from gas-phase TiCl{sub 4}

    SciTech Connect

    Hague, C.F.; Tronc, M.; De Groot, F.

    1997-04-01

    Resonant x-ray emission spectroscopy (RXES) has proved to be a powerful tool for studying the electronic structure of condensed matter. Over the past few years it has been used mainly for studying the valence bands of solids and condensed molecules. Very recently the advent of high brightness photon beams provided by third generation synchrotron radiation source undulators, associated with efficient x-ray emission spectrometers has made it possible to perform experiments on free diatomic molecular systems. RXE spectra of free molecules are of prime importance to gain insight into their electronic structure and bonding as they reflect the symmetry of orbitals engaged in the two-electron, two-step process with the l = 0, {+-}2 parity-conserving selection rule, and are free from solid state effects which can introduce difficulties in the interpretation. They provide information (more so than XAS) on the core excited states, and, when performed at fixed incident photon energy as a function of the emitted photon energy, on the electronic excitation (charge transfer, multiplet states). Moreover the anisotropy of the angular distribution of resonant x-ray emission affects the relative intensity of the emission peaks and provides information concerning the symmetries of final states. This is a preliminary report on what are the first RXE spectra of a 3d transition metal complex in the gas phase. The experiment concerns the Ti 3d {yields}2p emission spectrum of TiCl{sub 4} over the 450 to 470 eV region.

  19. Photoisomerization of β-Ionone Protonated Schiff Base in the Gas Phase.

    PubMed

    Coughlan, Neville J A; Wallace, Claire M; Adamson, Brian D; Bieske, Evan J

    2016-08-25

    The photoisomerization of β-ionone protonated Schiff base (BIPSB) is investigated in the gas phase by irradiating mobility-selected ions in a tandem ion mobility spectrometer with tunable radiation. Four distinguishable isomers are produced by electrospray ionization whose structures are deduced from their collision cross sections and photoisomerization behavior along with density functional theory calculations. They include two geometric isomers of BIPSB with trans or cis configurations about the polyene chain's terminal C═N double bond, a bicyclic structure formed through electrocyclization of the polyene chain, and a Z-retro-γ-ionone isomer. Although trans-BIPSB and 9-cis-BIPSB have similar photoisomerization action spectra, with a maximum response at 375 nm, they photoconvert to different isomers. The trans-BIPSB isomer transforms to the bicyclic form upon exposure to light over the 320-400 nm range, whereas the cis-BIPSB isomer is prevented by steric hindrance from forming the bicyclic BIPSB isomer following irradiation and is proposed instead to form the 7,9-di-cis isomer. Neither the bicyclic isomer nor the Z-retro-γ-ionone isomer respond strongly to near-UV light. PMID:27483192

  20. Predicting protein-protein interactions in unbalanced data using the primary structure of proteins

    PubMed Central

    2010-01-01

    Background Elucidating protein-protein interactions (PPIs) is essential to constructing protein interaction networks and facilitating our understanding of the general principles of biological systems. Previous studies have revealed that int