Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning

Hopkins, Chad W., Le Grand, Scott, Walker, Ross C., Roitberg, Adrian E.·2015·Journal of Chemical Theory and Computation

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Abstract

Previous studies have shown that the method of hydrogen mass repartitioning (HMR) is a potentially useful tool for accelerating molecular dynamics (MD) simulations. By repartitioning the mass of heavy atoms into the bonded hydrogen atoms, it is possible to slow the highest-frequency motions of the macromolecule under study, thus allowing the time step of the simulation to be increased by up to a factor of 2. In this communication, we investigate further how this mass repartitioning allows the simulation time step to be increased in a stable fashion without significantly increasing discretization error. To this end, we ran a set of simulations with different time steps and mass distributions on a three-residue peptide to get a comprehensive view of the effect of mass repartitioning and time step increase on a system whose accessible phase space is fully explored in a relatively short amount of time. We next studied a 129-residue protein, hen egg white lysozyme (HEWL), to verify that the observed behavior extends to a larger, more-realistic, system. Results for the protein include structural comparisons from MD trajectories, as well as comparisons of pKa calculations via constant-pH MD. We also calculated a potential of mean force (PMF) of a dihedral rotation for the MTS [(1-oxyl-2,2,5,5-tetramethyl-pyrroline-3-methyl)methanethiosulfonate] spin label via umbrella sampling with a set of regular MD trajectories, as well as a set of mass-repartitioned trajectories with a time step of 4 fs. Since no significant difference in kinetics or thermodynamics is observed by the use of fast HMR trajectories, further evidence is provided that long-time-step HMR MD simulations are a viable tool for accelerating MD simulations for molecules of biochemical interest.

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Authors: Hopkins, C. W., Le Grand, S., Walker, R. C., & Roitberg, A. E.
Venue: Journal of Chemical Theory and Computation
Publisher: American Chemical Society (ACS)
Published: 2015-03-30
Volume: 11
Issue: 4
Pages: 1864-1874
ISSN: 1549-9618 (ISSN-L)
1549-9626
DOI: 10.1021/ct5010406
OpenAlex: W1969189143
Cited by: 1,355
References: 0
FWCI: 16.21
Type: journal article
Language: en
Open access: closed
Funders: Office of Cyberinfrastructure (OCI 07-25070, OCI-1147910)

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Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning

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