共查询到20条相似文献,搜索用时 15 毫秒
1.
Supriya Pratihar Prof. Dr. T. Michael Sabo Dr. David Ban Dr. R. Bryn Fenwick Dr. Stefan Becker Prof. Dr. Xavier Salvatella Prof. Dr. Christian Griesinger Prof. Dr. Donghan Lee 《Angewandte Chemie (International ed. in English)》2016,55(33):9567-9570
Protein dynamics occurring on a wide range of timescales play a crucial role in governing protein function. Particularly, motions between the globular rotational correlation time ( ) and 40 μs (supra‐ window), strongly influence molecular recognition. This supra‐ window was previously hidden, owing to a lack of experimental methods. Recently, we have developed a high‐power relaxation dispersion (RD) experiment for measuring kinetics as fast as 4 μs. For the first time, this method, performed under super‐cooled conditions, enabled us to detect a global motion in the first β‐turn of the third IgG‐binding domain of protein G (GB3), which was extrapolated to 371±115 ns at 310 K. Furthermore, the same residues show the plasticity in the model‐free residual dipolar coupling (RDC) order parameters and in an ensemble encoding the supra‐ dynamics. This β‐turn is involved in antibody binding, exhibiting the potential link of the observed supra‐ motion with molecular recognition. 相似文献
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Dr. Matthew D. Shannon Dr. Theint Theint Dr. Dwaipayan Mukhopadhyay Dr. Krystyna Surewicz Prof. Witold K. Surewicz Dr. Dominique Marion Dr. Paul Schanda Prof. Christopher P. Jaroniec 《Chemphyschem》2019,20(2):311-317
Microsecond to millisecond timescale backbone dynamics of the amyloid core residues in Y145Stop human prion protein (PrP) fibrils were investigated by using 15N rotating frame (R1ρ) relaxation dispersion solid-state nuclear magnetic resonance spectroscopy over a wide range of spin-lock fields. Numerical simulations enabled the experimental relaxation dispersion profiles for most of the fibril core residues to be modelled by using a two-state exchange process with a common exchange rate of 1000 s−1, corresponding to protein backbone motion on the timescale of 1 ms, and an excited-state population of 2 %. We also found that the relaxation dispersion profiles for several amino acids positioned near the edges of the most structured regions of the amyloid core were better modelled by assuming somewhat higher excited-state populations (∼5–15 %) and faster exchange rate constants, corresponding to protein backbone motions on the timescale of ∼100–300 μs. The slow backbone dynamics of the core residues were evaluated in the context of the structural model of human Y145Stop PrP amyloid. 相似文献
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The Energetics of a Three‐State Protein Folding System Probed by High‐Pressure Relaxation Dispersion NMR Spectroscopy 下载免费PDF全文
Dr. Vitali Tugarinov Dr. David S. Libich Dr. Virginia Meyer Dr. Julien Roche Dr. G. Marius Clore 《Angewandte Chemie (International ed. in English)》2015,54(38):11157-11161
The energetic and volumetric properties of a three‐state protein folding system, comprising a metastable triple mutant of the Fyn SH3 domain, have been investigated using pressure‐dependent 15N‐relaxation dispersion NMR from 1 to 2500 bar. Changes in partial molar volumes (ΔV) and isothermal compressibilities (ΔκT) between all the states along the folding pathway have been determined to reasonable accuracy. The partial volume and isothermal compressibility of the folded state are 100 mL mol?1 and 40 μL mol?1 bar?1, respectively, higher than those of the unfolded ensemble. Of particular interest are the findings related to the energetic and volumetric properties of the on‐pathway folding intermediate. While the latter is energetically close to the unfolded state, its volumetric properties are similar to those of the folded protein. The compressibility of the intermediate is larger than that of the folded state reflecting the less rigid nature of the former relative to the latter. 相似文献
4.
The amplitudes of the relaxation curves, as obtained by the Temperature-jump method have been used to measure simultaneously equilibrium constant and enthalpy for the reaction of complex formation of Ni2+ ion by 2,6-dihydroxobenzoic acid in the presence of a buffer. The experiments have been performed by changing the concentration of metal ion at constant ligand concentration andpH as in a complexometric titration. The points of such ‘dynamic titrations’ have been analysed by means of the concept of ‘normal reactions’ which enabled us to transform a set of coupled individual steps into a set of kinetically independent reactions. The potentialities of the dynamic titrations are discussed. 相似文献
5.
Apparently contradictory statements about the thermodynamics of aqueous protein solutions and of hydrophobic effect are quoted and discussed. Some credibility is found in the divergent points of view and it is pointed out that they focus attention on different aspects of the complicated conditions in aqueous solutions, some of which are more important than others for the stability of protein conformations.The importance of characteristics of solvent water is emphasized, in particular (1) the strong mutual cohesion of water molecules, and (2) structural changes of water induced by (nonpolar) solute molecules. It is stressed that consideration of only one of these effects and an inexpedient choice of standard states are origins of confusion in the literature about aqueous systems. A simple approach to hydrophobic effects considering both of the above mentioned effects, is proposed. 相似文献
6.
Shiho Ohno Noriyoshi Manabe Takumi Yamaguchi Jun Uzawa Yoshiki Yamaguchi 《Molecules (Basel, Switzerland)》2021,26(18)
Ribitol (C5H12O5), an acyclic sugar alcohol, is present on mammalian α-dystroglycan as a component of O-mannose glycan. In this study, we examine the conformation and dynamics of ribitol by database analysis, experiments, and computational methods. Database analysis reveals that the anti-conformation (180°) is populated at the C3–C4 dihedral angle, while the gauche conformation (±60°) is seen at the C2–C3 dihedral angle. Such conformational asymmetry was born out in a solid-state 13C-NMR spectrum of crystalline ribitol, where C1 and C5 signals are unequal. On the other hand, solution 13C-NMR has identical chemical shifts for C1 and C5. NMR 3J coupling constants and OH exchange rates suggest that ribitol is an equilibrium of conformations, under the influence of hydrogen bonds and/or steric hinderance. Molecular dynamics (MD) simulations allowed us to discuss such a chemically symmetric molecule, pinpointing the presence of asymmetric conformations evidenced by the presence of correlations between C2–C3 and C3–C4 dihedral angles. These findings provide a basis for understanding the dynamic structure of ribitol and the function of ribitol-binding enzymes. 相似文献
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Clemens Kauffmann Dr. Anna Zawadzka-Kazimierczuk Dr. Georg Kontaxis Prof. Robert Konrat 《Chemphyschem》2021,22(1):18-28
Crucial to the function of proteins is their existence as conformational ensembles sampling numerous and structurally diverse substates. Despite this widely accepted notion there is still a high demand for meaningful and reliable approaches to characterize protein ensembles in solution. As it is usually conducted in solution, NMR spectroscopy offers unique possibilities to address this challenge. Particularly, cross-correlated relaxation (CCR) effects have long been established to encode both protein structure and dynamics in a compelling manner. However, this wealth of information often limits their use in practice as structure and dynamics might prove difficult to disentangle. Using a modern Maximum Entropy (MaxEnt) reweighting approach to interpret CCR rates of Ubiquitin, we demonstrate that these uncertainties do not necessarily impair resolving CCR-encoded structural information. Instead, a suitable balance between complementary CCR experiments and prior information is found to be the most crucial factor in mapping backbone dihedral angle distributions. Experimental and systematic deviations such as oversimplified dynamics appear to be of minor importance. Using Ubiquitin as an example, we demonstrate that CCR rates are capable of characterizing rigid and flexible residues alike, indicating their unharnessed potential in studying disordered proteins. 相似文献
9.
Martin Hoefling Francesco Iori Dr. Stefano Corni Dr. Kay‐Eberhard Gottschalk Dr. 《Chemphyschem》2010,11(8):1763-1767
The interactions of amino acids with inorganic surfaces are of interest for biologists and biotechnologists alike. However, the structural determinants of peptide–surface interactions have remained elusive, but are important for a structural understanding of the interactions of biomolecules with gold surfaces. Molecular dynamics simulations are a tool to analyze structures of amino acids on surfaces. However, such an approach is challenging due to lacking parameterization for many surfaces and the polarizability of metal surfaces. Herein, we report DFT calculations of amino acid fragments in vacuo and molecular dynamics simulations of the interaction of all amino acids with a gold(111) surface in explicit solvent, using the recently introduced polarizable gold force field GolP. We describe preferred orientations of the amino acids on the metal surface. We find that all amino acids preferably interact with the gold surface at least partially with their backbone, underlining an unfolding propensity of gold surfaces. 相似文献
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Cross-correlated relaxation (CCR) in multiple-quantum coherences differs from other relaxation phenomena in its theoretical ability to be mediated across an infinite distance. The two interfering relaxation mechanisms may be dipolar interactions, chemical shift anisotropies, chemical shift modulations or quadrupolar interactions. These properties make multiple-quantum CCR an attractive probe for structure and dynamics of biomacromolecules not accessible from other measurements. Here, we review the use of multiple-quantum CCR measurements in dynamics studies of proteins. We compile a list of all experiments proposed for CCR rate measurements, provide an overview of the theory with a focus on protein dynamics, and present applications to various protein systems. 相似文献
12.
《Angewandte Chemie (International ed. in English)》2017,56(1):380-383
Detergents are often used to investigate the structure and dynamics of membrane proteins. Whereas the structural integrity seems to be preserved in detergents for many membrane proteins, their functional activity is frequently compromised, but can be restored in a lipid environment. Herein we show with per‐residue resolution that while OmpX forms a stable β‐barrel in DPC detergent micelles, DHPC/DMPC bicelles, and DMPC nanodiscs, the pico‐ to nanosecond and micro‐ to millisecond motions differ substantially between the detergent and lipid environment. In particular for the β‐strands, there is pronounced dynamic variability in the lipid environment, which appears to be suppressed in micelles. This unexpected complex and membrane‐mimetic‐dependent dynamic behavior indicates that the frequent loss of membrane protein activity in detergents might be related to reduced internal dynamics and that membrane protein activity correlates with lipid flexibility. 相似文献
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Rapid Determination of Fast Protein Dynamics from NMR Chemical Exchange Saturation Transfer Data 下载免费PDF全文
Yina Gu Dr. Alexandar L. Hansen Dr. Yu Peng Prof. Dr. Rafael Brüschweiler 《Angewandte Chemie (International ed. in English)》2016,55(9):3117-3119
Functional motions of 15N‐labeled proteins can be monitored by solution NMR spin relaxation experiments over a broad range of timescales. These experiments however typically take of the order of several days to a week per protein. Recently, NMR chemical exchange saturation transfer (CEST) experiments have emerged to probe slow millisecond motions complementing R1ρ and CPMG‐type experiments. CEST also simultaneously reports on site‐specific R1 and R2 parameters. It is shown here how CEST‐derived R1 and R2 relaxation parameters can be measured within a few hours at an accuracy comparable to traditional relaxation experiments. Using a “lean” version of the model‐free approach S2 order parameters can be determined that match those from the standard model‐free approach applied to 15N R1, R2, and {1H}‐15N NOE data. The new methodology, which is demonstrated for ubiquitin and arginine kinase (42 kDa), should serve as an effective screening tool of protein dynamics from picosecond‐to‐millisecond timescales. 相似文献
15.
Dr. Sara Pellegrino Dr. Alessandro Contini Prof. Francesca Clerici Dr. Alessandro Gori Donatella Nava Prof. Maria Luisa Gelmi 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(28):8705-8715
A very efficient synthesis of orthogonally protected 1H‐azepine‐4‐amino‐4‐carboxylic acid, abbreviated as Azn, a conformationally restricted analogue of ornithine, was realized. It was obtained on a gram scale in good overall yield in five steps, three of which did not require isolation of the intermediates, starting from the readily available 1‐amino‐4‐oxo‐cyclohexane‐4‐carboxylic acid. Both enantiomers were used for the preparation of pentapeptide models containing Ala, Aib, and Azn. Conformational studies using both spectroscopic techniques (NMR, CD) and molecular dynamics on model 5‐mer peptides showed that the (R)‐Azn isomer possesses a marked helicogenic effect. 相似文献
16.
用分子力学方法对甾族抗炎药物进行了构象分析,并研究了该类化合物的构象与活性的相关性。结果表明,不仅在特写位置上的取代,而且氧原子的空间位置及空间能均是影响该类化合物活性的重要因素。 相似文献
17.
Probing Transient Conformational States of Proteins by Solid‐State R1ρ Relaxation‐Dispersion NMR Spectroscopy 下载免费PDF全文
Dr. Peixiang Ma Jens D. Haller Jérémy Zajakala Dr. Pavel Macek Dr. Astrid C. Sivertsen Prof. Dr. Dieter Willbold Dr. Jérôme Boisbouvier Dr. Paul Schanda 《Angewandte Chemie (International ed. in English)》2014,53(17):4312-4317
The function of proteins depends on their ability to sample a variety of states differing in structure and free energy. Deciphering how the various thermally accessible conformations are connected, and understanding their structures and relative energies is crucial in rationalizing protein function. Many biomolecular reactions take place within microseconds to milliseconds, and this timescale is therefore of central functional importance. Here we show that R1ρ relaxation dispersion experiments in magic‐angle‐spinning solid‐state NMR spectroscopy make it possible to investigate the thermodynamics and kinetics of such exchange process, and gain insight into structural features of short‐lived states. 相似文献
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Dr. Xiaowang Zhou Dr. Shinyoung Kang Dr. Tae Wook Heo Dr. Brandon C. Wood Dr. Vitalie Stavila Dr. Mark D. Allendorf 《Chemphyschem》2019,20(10):1404-1411
Magnesium-based materials provide some of the highest capacities for solid-state hydrogen storage. However, efforts to improve their performance rely on a comprehensive understanding of thermodynamic and kinetic limitations at various stages of (de)hydrogenation. Part of the complexity arises from the fact that unlike interstitial metal hydrides that retain the same crystal structures of the underlying metals, MgH2 and other magnesium-based hydrides typically undergo dehydrogenation reactions that are coupled to a structural phase transformation. As a first step towards enabling molecular dynamics studies of thermodynamics, kinetics, and (de)hydrogenation mechanisms of Mg-based solid-state hydrogen storage materials with changing crystal structures, we have developed an analytical bond order potential for Mg−H systems. We demonstrate that our potential accurately reproduces property trends of a variety of elemental and compound configurations with different coordinations, including small clusters and bulk lattices. More importantly, we show that our potential captures the relevant (de)hydrogenation chemical reactions 2H (gas)→H2 (gas) and 2H (gas)+Mg (hcp)→MgH2 (rutile) within molecular dynamics simulations. This verifies that our potential correctly prescribes the lowest Gibbs free energies to the equilibrium H2 and MgH2 phases as compared to other configurations. It also indicates that our molecular dynamics methods can directly reveal atomic processes of (de)hydrogenation of the Mg−H systems. 相似文献
20.
The vibrational and rotational mode-specific relaxations of CH3NO2 with 50 kcal/mol of initial internal energy in an argon bath is computed at 300 K at pressures of 10-400 atm. This work uses archived information from our previously published [J. Chem. Phys. 142, 014303 (2015)] molecular dynamics simulations and employs our previous published [J. Chem. Phys. 151, 034303 (2019)] method for projecting time-dependent Cartesian velocities onto normal mode eigenvectors. The computed relaxations cover three types of energies: vibrational, rotational, and Coriolis. In general, rotational and Coriolis relaxations in all modes are initially fast followed by an orders of magnitude slower relaxation. For all modes, that slower relaxation rate is approximately comparable to the vibrational relaxation rate. For all three types of energies, there are small-scale mode-to-mode variations. Of particular prominence is the exceptionally fast relaxation shared in common by the external rotation about the C N axis, the internal hindered rotation of the CH3 group relative to the NO2 group, and the symmetric stretch of the CH3 group. 相似文献