skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Protein Under Pressure: Molecular Dynamics Simulation of the Arc Repressor

Abstract

Experimental nuclear magnetic resonance results for the Arc Repressor have shown that this dimeric protein dissociates into a molten globule at high pressure. This structural change is accompanied by a modification of the hydrogenbonding pattern of the intermolecular -sheet: it changes its character from intermolecular to intramolecular with respect to the two monomers. Molecular dynamics simulations of the Arc Repressor, as a monomer and a dimer, at elevated pressure have been performed with the aim to study this hypothesis and to identify the major structural and dynamical changes of the protein under such conditions. The monomer appears less stable than the dimer. However, the complete dissociation has not been seen because of the long timescale needed to observe this phenomenon. In fact, the protein structure altered very little when increasing the pressure. It became slightly compressed and the dynamics of the side-chains and the unfolding process slowed down. Increasing both, temperature and pressure, a tendency of conversion of intermolecular into intramolecular hydrogen bonds in the -sheet region has been detected, supporting the mentioned hypothesis. Also, the onset of denaturation of the separated chains was observed.

Authors:
; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
920552
Report Number(s):
PNNL-SA-51875
TRN: US200818%%702
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proteins. Structure, Function, and Bioinformatics, 65(1):136-144; Journal Volume: 65; Journal Issue: 1
Country of Publication:
United States
Language:
English
Subject:
08 HYDROGEN; BONDING; CHAINS; DISSOCIATION; HYDROGEN; HYPOTHESIS; MODIFICATIONS; MONOMERS; NUCLEAR MAGNETIC RESONANCE; PROTEIN STRUCTURE; PROTEINS; SIMULATION

Citation Formats

Trzesniak, Daniel Rodrigo F., Lins, Roberto D., and van Gunsteren, Wilfred F. Protein Under Pressure: Molecular Dynamics Simulation of the Arc Repressor. United States: N. p., 2006. Web. doi:10.1002/prot.21034.
Trzesniak, Daniel Rodrigo F., Lins, Roberto D., & van Gunsteren, Wilfred F. Protein Under Pressure: Molecular Dynamics Simulation of the Arc Repressor. United States. doi:10.1002/prot.21034.
Trzesniak, Daniel Rodrigo F., Lins, Roberto D., and van Gunsteren, Wilfred F. 2006. "Protein Under Pressure: Molecular Dynamics Simulation of the Arc Repressor". United States. doi:10.1002/prot.21034.
@article{osti_920552,
title = {Protein Under Pressure: Molecular Dynamics Simulation of the Arc Repressor},
author = {Trzesniak, Daniel Rodrigo F. and Lins, Roberto D. and van Gunsteren, Wilfred F.},
abstractNote = {Experimental nuclear magnetic resonance results for the Arc Repressor have shown that this dimeric protein dissociates into a molten globule at high pressure. This structural change is accompanied by a modification of the hydrogenbonding pattern of the intermolecular -sheet: it changes its character from intermolecular to intramolecular with respect to the two monomers. Molecular dynamics simulations of the Arc Repressor, as a monomer and a dimer, at elevated pressure have been performed with the aim to study this hypothesis and to identify the major structural and dynamical changes of the protein under such conditions. The monomer appears less stable than the dimer. However, the complete dissociation has not been seen because of the long timescale needed to observe this phenomenon. In fact, the protein structure altered very little when increasing the pressure. It became slightly compressed and the dynamics of the side-chains and the unfolding process slowed down. Increasing both, temperature and pressure, a tendency of conversion of intermolecular into intramolecular hydrogen bonds in the -sheet region has been detected, supporting the mentioned hypothesis. Also, the onset of denaturation of the separated chains was observed.},
doi = {10.1002/prot.21034},
journal = {Proteins. Structure, Function, and Bioinformatics, 65(1):136-144},
number = 1,
volume = 65,
place = {United States},
year = 2006,
month =
}
  • Molecular dynamics simulations of a crystalline protein, Staphylococcal nuclease, over the pressure range 1 bar to 15 kbar reveal a qualitative change in the internal protein motions at {approx_equal}4 kbar. This change involves the existence of two linear regimes in the mean-square displacement for internal protein motion, <u{sup 2}>(P) with a twofold decrease in the slope for P>4 kbar. The major effect of pressure on the dynamics is a loss, with increasing pressure of large amplitude, collective protein modes below 2 THz effective frequency, accompanied by restriction of large-scale solvent translational motion.
  • Microscopic statistical pressure fluctuations can, in principle, lead to corresponding fluctuations in the shape of a protein energy landscape. To examine this, nanosecond molecular dynamics simulations of lysozyme are performed covering a range of temperatures and pressures. The well known dynamical transition with temperature is found to be pressure-independent, indicating that the effective energy barriers separating conformational substates are not significantly influenced by pressure. In contrast, vibrations within substates stiffen with pressure, due to increased curvature of the local harmonic potential in which the atoms vibrate. The application of pressure is also shown to selectively increase the damping of themore » anharmonic, low-frequency collective modes in the protein, leaving the more local modes relatively unaffected. The critical damping frequency, i.e., the frequency at which energy is most efficiently dissipated, increases linearly with pressure. The results suggest that an invariant description of protein energy landscapes should be subsumed by a fluctuating picture and that this may have repercussions in, for example, mechanisms of energy dissipation accompanying functional, structural, and chemical relaxation.« less
  • Microscopic statistical pressure fluctuations can, in principle, lead to corresponding fluctuations in the shape of a protein energy landscape. To examine this, nanosecond molecular dynamics simulations of lysozyme are performed covering a range of temperatures and pressures. The well known dynamical transition with temperature is found to be pressure-independent, indicating that the effective energy barriers separating conformational substates are not significantly influenced by pressure. In contrast, vibrations within substates stiffen with pressure, due to increased curvature of the local harmonic potential in which the atoms vibrate. The application of pressure is also shown to selectively increase the damping of themore » anharmonic, low-frequency collective modes in the protein, leaving the more local modes relatively unaffected. The critical damping frequency, i.e., the frequency at which energy is most efficiently dissipated, increases linearly with pressure. The results suggest that an invariant description of protein energy landscapes should be subsumed by a fluctuating picture and that this may have repercussions in, for example, mechanisms of energy dissipation accompanying functional, structural, and chemical relaxation.« less
  • High-pressure induced zinc blende to rocksalt phase transition in GaN has been investigated by ab initio molecular dynamics method to characterize the transformation mechanism at the atomic level. It was shown that at 100 GPa GaN passes through tetragonal and monoclinic states before rocksalt structure is formed. The transformation mechanism is consistent with that for other zinc blende semiconductors obtained from the same method. Detailed structural analysis showed that there is no bond breaking involved in the phase transition.
  • The dynamical origin of the x-ray diffuse scattering by crystals of a protein, Staphylococcal nuclease, is determined using molecular dynamics simulation. A smooth, nearly isotropic scattering shell at q=0.28 A ring {sup -1} originates from equal contributions from correlations in nearest-neighbor water molecule dynamics and from internal protein motions, the latter consisting of {alpha}-helix pitch and inter-{beta}-strand fluctuations. Superposed on the shell are intense, three-dimensional scattering features that originate from a very small number of slowly varying (>10 ns) collective motions. The individual three-dimensional features are assigned to specific collective motions in the protein, and some of these explicitly involvemore » potentially functional active-site deformations.« less