Accelerating Kinetics with Time-reversal Path Sampling (2307.12214v2)

Abstract: In comparison to numerous enhanced sampling methods for equilbrium thermodynamics, accelerating simulations for kinetics and nonequilibrium statistics are relatively rare and less effective. Here we derive a time-reversal path sampling (tRPS) method based on the time reversibility to accelerate simulations for determining the transition rates between free-ernegy basins. It converts the difficult up-hill path sampling into an easy down-hill problem. The method is easy to implement, i.e., forward and backward shooting simulations with opposite initial velocities are conducted from random initial conformations within a transition-state region until they reach the basin minima, which are then assembled to give the distribution of transition paths efficiently. The effects of tRPS are demonstrated by comparison with direct simulations on protein folding and unfolding, where tRPS is shown to give results consistent with direct simulations and increase the efficiency by up to five orders of magnitude. The approach is generally applicable to stochatic processes with microscopic reversibility, no mater whether the variables are continuous or discrete.