Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems

Radak, Brian K.; Chipot, Christophe; Suh, Donghyuk; Jo, Sunhwan; Jiang, Wei; Phillips, James C.; Schulten, Klaus; Roux, Benoit

doi:10.1021/acs.jctc.7b00875

Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems

Journal Article · Mon Nov 06 23:00:00 EST 2017 · Journal of Chemical Theory and Computation

DOI:https://doi.org/10.1021/acs.jctc.7b00875· OSTI ID:1421956

^[1]; ^[2]; Suh, Donghyuk ^[3]; Jo, Sunhwan ^[1]; Jiang, Wei ^[1]; Phillips, James C. ^[4]; Schulten, Klaus ^[5]; ^[6]

Argonne National Lab. (ANL), Argonne, IL (United States). Leadership Computing Facility
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
Univ. of Chicago, IL (United States). Department of Chemistry
University of Illinois at Urbana−Champaign, Urbana, IL (United States). Theoretical and Computational Biophysics Group, Beckman Institute for Advanced Science and Technology
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
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

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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE; Argonne National Laboratory, Argonne Leadership Computing Facility, Early Science Program; National Institutes of Health (NIH) - National Institute of General Medical Sciences

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1421956

Journal Information:: Journal of Chemical Theory and Computation, Journal Name: Journal of Chemical Theory and Computation Journal Issue: 12 Vol. 13; ISSN 1549-9618

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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Constant-pH Molecular Dynamics Simulations for Large Biomolecular Systems

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