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

Title: Quasiharmonic analysis of protein energy landscapes from pressure-temperature molecular dynamics simulations

Authors:
 [1];  [2]; ORCiD logo [1]
  1. Department of Chemistry, Georgetown University, Washington, DC 20057, USA
  2. Department of Civil and Environmental Engineering, The George Washington University, Washington, DC 20052, USA
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1395194
Grant/Contract Number:
NA-0002006
Resource Type:
Journal Article: Publisher's Accepted Manuscript
Journal Name:
Journal of Chemical Physics
Additional Journal Information:
Journal Volume: 147; Journal Issue: 12; Related Information: CHORUS Timestamp: 2018-02-14 14:22:17; Journal ID: ISSN 0021-9606
Publisher:
American Institute of Physics
Country of Publication:
United States
Language:
English

Citation Formats

Rodgers, Jocelyn M., Hemley, Russell J., and Ichiye, Toshiko. Quasiharmonic analysis of protein energy landscapes from pressure-temperature molecular dynamics simulations. United States: N. p., 2017. Web. doi:10.1063/1.5003823.
Rodgers, Jocelyn M., Hemley, Russell J., & Ichiye, Toshiko. Quasiharmonic analysis of protein energy landscapes from pressure-temperature molecular dynamics simulations. United States. doi:10.1063/1.5003823.
Rodgers, Jocelyn M., Hemley, Russell J., and Ichiye, Toshiko. 2017. "Quasiharmonic analysis of protein energy landscapes from pressure-temperature molecular dynamics simulations". United States. doi:10.1063/1.5003823.
@article{osti_1395194,
title = {Quasiharmonic analysis of protein energy landscapes from pressure-temperature molecular dynamics simulations},
author = {Rodgers, Jocelyn M. and Hemley, Russell J. and Ichiye, Toshiko},
abstractNote = {},
doi = {10.1063/1.5003823},
journal = {Journal of Chemical Physics},
number = 12,
volume = 147,
place = {United States},
year = 2017,
month = 9
}

Journal Article:
Free Publicly Available Full Text
This content will become publicly available on September 27, 2018
Publisher's Accepted Manuscript

Save / Share:
  • Quasiharmonic-lattice-dynamics and molecular-dynamics calculations were performed on metallic sodium from the low-temperature region to above melting at several different volumes. A pseudopotential model was used that consisted of a large volume-dependent potential plus a small effective two-body potential. From the molecular-dynamics results for the solid phase, we have constructed the Helmholtz free energy and calculated the thermodynamic properties up to the melting temperature. The anharmonic contributions to the internal energy and pressure are determined directly from molecular dynamics without using thermodynamic perturbation theory. Calculated and experimental values of the zero-pressure volume-temperature curve, isothermal bulk modulus, heat capacity, and Grueneisen parametermore » are found to be in good agreement. We conclude that the pseudopotential model provides an accurate representation of the potential for energies up to melt; molecular-dynamics simulations accurately represent the classical vibrational contributions to the thermodynamic functions at high temperatures and give a meaningful evaluation of the anharmonicity. The combination of quasiharmonic-lattice-dynamic theory in the quantum regime and molecular dynamics in the classical regime provide a simple and natural representation of the vibrational thermodynamics of a solid.« 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
  • 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
  • X-ray diffraction from protein crystals includes both sharply peaked Bragg reflections and diffuse intensity between the peaks. The information in Bragg scattering is limited to what is available in the mean electron density. The diffuse scattering arises from correlations in the electron density variations and therefore contains information about collective motions in proteins. Previous studies using molecular-dynamics (MD) simulations to model diffuse scattering have been hindered by insufficient sampling of the conformational ensemble. To overcome this issue, we have performed a 1.1-μs MD simulation of crystalline staphylococcal nuclease, providing 100-fold more sampling than previous studies. This simulation enables reproducible calculationsmore » of the diffuse intensity and predicts functionally important motions, including transitions among at least eight metastable states with different active-site geometries. The total diffuse intensity calculated using the MD model is highly correlated with the experimental data. In particular, there is excellent agreement for the isotropic component of the diffuse intensity, and substantial but weaker agreement for the anisotropic component. The decomposition of the MD model into protein and solvent components indicates that protein–solvent interactions contribute substantially to the overall diffuse intensity. In conclusion, diffuse scattering can be used to validate predictions from MD simulations and can provide information to improve MD models of protein motions.« less
  • X-ray diffraction from protein crystals includes both sharply peaked Bragg reflections and diffuse intensity between the peaks. The information in Bragg scattering is limited to what is available in the mean electron density. The diffuse scattering arises from correlations in the electron density variations and therefore contains information about collective motions in proteins. Previous studies using molecular-dynamics (MD) simulations to model diffuse scattering have been hindered by insufficient sampling of the conformational ensemble. To overcome this issue, we have performed a 1.1-μs MD simulation of crystalline staphylococcal nuclease, providing 100-fold more sampling than previous studies. This simulation enables reproducible calculationsmore » of the diffuse intensity and predicts functionally important motions, including transitions among at least eight metastable states with different active-site geometries. The total diffuse intensity calculated using the MD model is highly correlated with the experimental data. In particular, there is excellent agreement for the isotropic component of the diffuse intensity, and substantial but weaker agreement for the anisotropic component. The decomposition of the MD model into protein and solvent components indicates that protein–solvent interactions contribute substantially to the overall diffuse intensity. In conclusion, diffuse scattering can be used to validate predictions from MD simulations and can provide information to improve MD models of protein motions.« less
    Cited by 21