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Title: Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems

Abstract

We report that an increasingly important endeavor is to develop computational strategies that enable molecular dynamics (MD) simulations of biomolecular systems with spontaneous changes in protonation states under conditions of constant pH. The present work describes our efforts to implement the powerful constant-pH MD simulation method, based on a hybrid nonequilibrium MD/Monte Carlo (neMD/MC) technique within the highly scalable program NAMD. The constant-pH hybrid neMD/MC method has several appealing features; it samples the correct semigrand canonical ensemble rigorously, the computational cost increases linearly with the number of titratable sites, and it is applicable to explicit solvent simulations. The present implementation of the constant-pH hybrid neMD/MC in NAMD is designed to handle a wide range of biomolecular systems with no constraints on the choice of force field. Furthermore, the sampling efficiency can be adaptively improved on-the-fly by adjusting algorithmic parameters during the simulation. Finally, illustrative examples emphasizing medium- and large-scale applications on next-generation supercomputing architectures are provided.

Authors:
ORCiD logo [1]; ORCiD logo [2];  [3];  [1];  [1];  [4];  [5]; ORCiD logo [6]
  1. Argonne National Lab. (ANL), Argonne, IL (United States). Leadership Computing Facility
  2. Université de Lorraine (France). Laboratoire International Associé Centre National de la Recherche Scientifique et University of Illinois at Urbana−Champaign; University of Illinois at Urbana−Champaign, Urbana, IL (United States). Dept. of Physics
  3. Univ. of Chicago, IL (United States). Department of Chemistry
  4. University of Illinois at Urbana−Champaign, Urbana, IL (United States). Theoretical and Computational Biophysics Group, Beckman Institute for Advanced Science and Technology
  5. University of Illinois at Urbana−Champaign, Urbana, IL (United States). Theoretical and Computational Biophysics Group, Beckman Institute for Advanced Science and Technology and Department of Physics
  6. Univ. of Chicago, IL (United States). Department of Biochemistry and Molecular Biology and Department of Chemistry; Argonne National Lab. (ANL), Argonne, IL (United States). Center for Nanoscale Materials
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE; Argonne National Laboratory, Argonne Leadership Computing Facility, Early Science Program; National Institutes of Health (NIH) - National Institute of General Medical Sciences
OSTI Identifier:
1421956
Grant/Contract Number:
AC02-06CH11357
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of Chemical Theory and Computation
Additional Journal Information:
Journal Volume: 13; Journal Issue: 12; Journal ID: ISSN 1549-9618
Publisher:
American Chemical Society
Country of Publication:
United States
Language:
English
Subject:
97 MATHEMATICS AND COMPUTING; 59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; hybrid Monte Carlo/molecular dynamics; nonequilibrium

Citation Formats

Radak, Brian K., Chipot, Christophe, Suh, Donghyuk, Jo, Sunhwan, Jiang, Wei, Phillips, James C., Schulten, Klaus, and Roux, Benoit. Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems. United States: N. p., 2017. Web. doi:10.1021/acs.jctc.7b00875.
Radak, Brian K., Chipot, Christophe, Suh, Donghyuk, Jo, Sunhwan, Jiang, Wei, Phillips, James C., Schulten, Klaus, & Roux, Benoit. Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems. United States. doi:10.1021/acs.jctc.7b00875.
Radak, Brian K., Chipot, Christophe, Suh, Donghyuk, Jo, Sunhwan, Jiang, Wei, Phillips, James C., Schulten, Klaus, and Roux, Benoit. Tue . "Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems". United States. doi:10.1021/acs.jctc.7b00875.
@article{osti_1421956,
title = {Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems},
author = {Radak, Brian K. and Chipot, Christophe and Suh, Donghyuk and Jo, Sunhwan and Jiang, Wei and Phillips, James C. and Schulten, Klaus and Roux, Benoit},
abstractNote = {We report that an increasingly important endeavor is to develop computational strategies that enable molecular dynamics (MD) simulations of biomolecular systems with spontaneous changes in protonation states under conditions of constant pH. The present work describes our efforts to implement the powerful constant-pH MD simulation method, based on a hybrid nonequilibrium MD/Monte Carlo (neMD/MC) technique within the highly scalable program NAMD. The constant-pH hybrid neMD/MC method has several appealing features; it samples the correct semigrand canonical ensemble rigorously, the computational cost increases linearly with the number of titratable sites, and it is applicable to explicit solvent simulations. The present implementation of the constant-pH hybrid neMD/MC in NAMD is designed to handle a wide range of biomolecular systems with no constraints on the choice of force field. Furthermore, the sampling efficiency can be adaptively improved on-the-fly by adjusting algorithmic parameters during the simulation. Finally, illustrative examples emphasizing medium- and large-scale applications on next-generation supercomputing architectures are provided.},
doi = {10.1021/acs.jctc.7b00875},
journal = {Journal of Chemical Theory and Computation},
number = 12,
volume = 13,
place = {United States},
year = {Tue Nov 07 00:00:00 EST 2017},
month = {Tue Nov 07 00:00:00 EST 2017}
}

Journal Article:
Free Publicly Available Full Text
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