Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning

作者：Chad W. Hopkins, Scott Le Grand, Ross C. Walker, Adrián E. Roitberg · 发表于：Journal of Chemical Theory and Computation · 年份：2015 · DOI：10.1021/ct5010406 · 被引用次数：1574 · 研究领域：Protein Structure and Dynamics、Spectroscopy and Quantum Chemical Studies、Molecular spectroscopy and chirality

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...