Highly parallelizable path sampling with minimal rejections using asynchronous replica exchange and infinite swaps

Abstract

Capturing rare yet pivotal events poses a significant challenge for molecular simulations. Path sampling provides a unique approach to tackle this issue without altering the potential energy landscape or dynamics, enabling recovery of both thermodynamic and kinetic information. However, despite its exponential acceleration compared to standard molecular dynamics, generating numerous trajectories can still require a long time. By harnessing our recent algorithmic innovations—particularly subtrajectory moves with high acceptance, coupled with asynchronous replica exchange featuring infinite swaps—we establish a highly parallelizable and rapidly converging path sampling protocol, compatible with diverse high-performance computing architectures. We demonstrate our approach on the liquid–vapor phase transition in superheated water, the unfolding of the chignolin protein, and water dissociation. The latter, performed at the ab initio level, achieves comparable statistical accuracy within days, in contrast to a previous study requiring over a year.