Approximating First Hitting Point Distribution in Milestoning for Rare Event Kinetics

Milestoning is an efficient method for rare event kinetics calculation using short trajectory parallelization. Mean first passage time (MFPT) is the key kinetic output of Milestoning, whose accuracy crucially depends on the initial distribution of the short trajectory ensemble. The true initial distribution, i.e., the first hitting point distribution (FHPD), has no analytic expression in the general case. Here, we introduce two algorithms, local passage time weighted Milestoning (LPT-M) and Bayesian inference Milestoning (BI-M), to accurately and efficiently approximate FHPD for systems at equilibrium condition. Starting from sampling the Boltzmann distribution on milestones, we calculate the proper weighting factor for the short trajectory ensemble. The methods are tested on two model examples for illustration purpose. Both methods improve significantly over the widely used classical Milestoning (CM) method in terms of the accuracy of MFPT. In particular, BI-M covers the directional Milestoning method as a special case in deterministic Hamiltonian dynamics. LPT-M is especially advantageous in terms of computational costs and robustness with respect to the increasing number of intermediate milestones. Furthermore, a locally iterative correction algorithm for nonequilibrium stationary FHPD is developed for exact MFPT calculation, which can be combined with LPT-M/BI-M and is much cheaper than the exact Milestoning (ExM) method.

Automated summary

This study investigates the application of Milestoning in rare event kinetics calculation. Two algorithms, LPT-M and BI-M, are proposed to accurately and efficiently approximate the initial distribution of the system. The results demonstrate that both methods outperform the classical Milestoning method in terms of accuracy and computational cost.