Generative methods for sampling transition paths in molecular dynamics

Molecular dynamics aims at simulating the physical movement of atoms in order to sample the Boltzmann-Gibbs probability measure and the associated trajectories, and to compute macroscopic properties using Monte Carlo estimates [17, 1]. One of the main difficulties when performing these numerical simulations is metastability: the system tends to stay trapped in some regions of the phase space, typically in the vicinity of local maxima of the target probability measure. In this context, transitions from one metastable state to another one are of particular interest in complex systems, as they characterize for example crystallisation or enzymatic reactions. These reactions happen on a long time scale compared to the molecular timescale, so that the simulation of realistic rare events is computationally difficult. On the one hand, many efforts have been devoted to the development of rare events sampling methods in molecular dynamics. The goal of these methods is to characterize transition paths and to compute associated transition rates and mean transition times; see for instance [21] for a review. The most notable methods can be classified in two groups: (i) importance sampling techniques, where the dynamics is biased (by modifying the potential for instance) to reduce the variance of Monte Carlo estimators when computing expectations, see for instance [16, 8] for more details, and also [31, Section 6.2]. It is possible to use adaptive importance sampling strategies to choose the importance function, see [30, Chapter 5]. Another viewpoint is offered by the framework of stochastic control, as in [21] where the modification in the drift of the dynamics is determined by the solution of an optimal control problem.