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Iwadate, Mitsuo; Asakura, Tetsuo; Dubovskii, Peter V.; Yamada, Hiroaki; Akasaka, Kazuyuki; Williamson, Michael P.

doi:10.1023/a:1008392327013

Cited by 31 publications

(17 citation statements)

References 27 publications

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“…The structural changes of comparable magnitude were reported in a crystalline protein at high pressure [10]. The important point here is that up to 2 kbar, the chemical shift changes of almost all 1 H and 15 N nuclei in hen lysozyme and BPTI are linear with pressure [14][15][16][17][19][20][21][22]. This means that linear conformational changes take place with pressure in both secondary and tertiary structures, and hence a linear volume change in Fig.…”

Section: Linear Compression Within the Same Subensemblesupporting

confidence: 72%

“…Microscopically, compression of a protein volume is accompanied by slight changes in local conformations, which can be studied most sensitively by NMR as chemical shift changes. We found by highpressure NMR in solution that the general compression of the native conformer is accompanied by increased side chain packing [14,15] and shortened hydrogen bond distances on the order of ~0.02 Å on average at 2 kbar [16][17][18][19][20][21], accompanied by slight changes in torsion angles of a few degrees on average in φ, ψ angles [22], all of which occur heterogeneously over the folded protein architecture. The structural changes of comparable magnitude were reported in a crystalline protein at high pressure [10].…”

Section: Linear Compression Within the Same Subensemblementioning

confidence: 98%

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Exploring the entire conformational space of proteins by high-pressure NMR

Akasaka

2003

Pure and Applied Chemistry

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A protein in solution is a thermodynamic entity, spanning, in principle, the entire allowed conformational space from the fully folded N to the fully unfolded U. Although some alternately or partially folded higher-energy conformers may coexist with N and U, they are seldom detected spectroscopically because their populations are usually quite low under physiological conditions. I describe here a new type of experiment, a combination of multidimensional NMR spectroscopy with pressure, that is capable of detecting and analyzing structures and thermodynamic stability of these higher-energy conformers. The idea is based on the finding that under physiological conditions the conformational order of a globular protein normally decreases in parallel with its partial molar volume (negative ∆V), so that under equilibrium conditions, the population is shifted to a less-and-less-ordered conformer with increasing pressure. In principle, with the high space resolution of the multidimensional NMR, the method enables one to explore protein structure and stability in atomic detail in a wide conformational space from N to U with pressure and temperature as variables. The method will provide us with a strong basis for understanding the fundamental phenomena of proteins: function, folding, and aggregation.

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Section: Linear Compression Within the Same Subensemblesupporting

confidence: 72%

Section: Linear Compression Within the Same Subensemblementioning

confidence: 98%

Exploring the entire conformational space of proteins by high-pressure NMR

Akasaka

2003

Pure and Applied Chemistry

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“…The changes in size of the ␣-helix are elastic; that is, they occur without changing significantly the ␣-helical structure (36,51). To explore size changes, we monitored the radius of gyration, R g , and the end-to-end distance, d end , of the peptide as a function of pressure.…”

Section: Resultsmentioning

confidence: 99%

“…Overall, high pressures will favor lower-volume configurations of the system. High-pressure studies of ␣-helical peptides suggest that ␣-helices preserve the helical structure at pressures up to 300 MPa (36). These experiments have motivated us to explore the pressure effects on the stability and hydration of peptides.…”

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confidence: 99%

Simulations of the pressure and temperature unfolding of an α-helical peptide

Paschek

Gnanakaran

Garcı́a

2005

Proc. Natl. Acad. Sci. U.S.A.

109

108

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We study by molecular simulations the reversible folding͞unfold-ing equilibrium as a function of density and temperature of a solvated ␣-helical peptide. We use an extension of the replica exchange molecular dynamics method that allows for density and temperature Monte Carlo exchange moves. We studied 360 thermodynamic states, covering a density range from 0.96 to 1.14 g⅐cm ؊3 and a temperature range from 300 to 547.6 K. We simulated 10 ns per replica for a total simulation time of 3.6 s. We characterize the structural, thermodynamic, and hydration changes as a function of temperature and pressure. We also calculate the compressibility and expansivity of unfolding. We find that pressure does not affect the helix-coil equilibrium significantly and that the volume change upon pressure unfolding is small and negative (؊2.3 ml͞mol). However, we find significant changes in the coordination of water molecules to the backbone carbonyls. This finding predicts that changes in the chemical shifts and IR spectra with pressure can be due to changes in coordination and not only changes in the helical content. A simulation of the IR spectrum shows that water coordination effects on frequency shifts are larger than changes due to elastic structural changes in the peptide.folding ͉ thermodynamics ͉ IR spectroscopy ͉ replica exchange molecular dynamics E nhanced sampling methods enable the sampling of the configurational space of proteins and peptides in an efficient way, overcoming sampling limitations due to the multiple time scales involved in protein folding (1). Umbrella sampling (2), replica exchange molecular dynamics (REMD) (3-5) [which can be derived as an umbrella sampling technique (6)], and multicanonical ensemble methods (7,8) are efficient methods for modeling thermodynamic equilibrium at the cost of kinetic information. With the development of equilibrium-enhanced sampling methods, we are able to validate (or invalidate) and modify semiempirical force fields and to explore the free-energy landscape of proteins and peptides (9, 10). The REMD method has been used to describe the energy landscape of peptides (9, 11-15), proteins (16), and protein membrane systems (17). For recent reviews, see refs. 1 and 6.In this work, we use an extension of REMD to describe pressure effects on the equilibrium helix-coil transition of an ␣-helical peptide. Similar to temperature exchanges, we can devise exchange rules for systems with different intensive thermodynamic parameters like density and its conjugate variable, pressure (18). Pressure effects on proteins are of interest in biotechnology and biology (19). Pressure effects are also of interest in the physical chemistry of proteins, because pressure provides a way of shifting equilibrium of protein configurations without increasing thermal fluctuations or changing the system composition (e.g., chemical unfolding) (20)(21)(22). Proteins undergo unfolding upon addition of pressures of Ͼ200 MPa (2 kbars; 1 bar ϭ 100 kPa). High pressures also are able to dissociate protein complexe...

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“…Variations of experimental chemical shifts were used to refine the BPTI [182], the lyzozyme [183] and the melittin [184] structures at high pressure. The starting conformation of the protein was a conformation determined at a pressure of 1 atm, and this conformation was deformed according to the variations of chemical shifts observed with increasing pressure.…”

Section: Chemical Shift Restraintsmentioning

confidence: 99%

Quantitative Analysis of Biomolecular NMR Spectra: A Prerequisite for the Determination of the Structure and Dynamics of Biomolecules

Malliavin

2006

COC

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Nuclear Magnetic Resonance (NMR) became during the two last decades an important method for biomolecular structure determination. NMR permits to study biomolecules in solution and gives access to the molecular flexibility at atomic level on a complete structure: in that respect, it is occupying a unique place i n structural biology. During the first years of its development, NMR was trying to meet the requirements previously defined in X-ray crystallography. But, NMR then started to determine its own criteria for the definition of a structure. Indeed, the atomic coordinates of an NMR structure are calculated using restraints on geometrical parameters (angles and distances) of the structure, which are only indirectly related to atom positions: in that respect, NMR and X-ray crystallography are very different. The indirect relation between the NMR measurements and the molecular structure and dynamics makes critical the precision and the interpretation of the NMR parameters and the development of quantitative analysis methods. The methods published since 1997 for liquid-NMR of proteins are reviewed here. First, methods for structure determination are presented, as well as methods for spectral assignment and for structure quality assessment. Second, the quantitative analysis of structure mobility i s reviewed.

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Cited by 31 publications

References 27 publications

Exploring the entire conformational space of proteins by high-pressure NMR

Exploring the entire conformational space of proteins by high-pressure NMR

Simulations of the pressure and temperature unfolding of an α-helical peptide

Quantitative Analysis of Biomolecular NMR Spectra: A Prerequisite for the Determination of the Structure and Dynamics of Biomolecules

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