Efficient Monte Carlo sampling of metastable systems using nonlocal collective variable updates

Abstract

Monte Carlo simulations are widely used to simulate complex molecular systems, but standard approaches suffer from metastability. Lately, the use of nonlocal proposal updates in a collective-variable (CV) space has been proposed in several works. Here, we generalize these approaches and explicitly spell out an algorithm for nonlinear CVs and underdamped Langevin dynamics. We prove reversibility of the resulting scheme and demonstrate its performance on several numerical examples, observing a substantial performance increase compared to methods based on overdamped Langevin dynamics as considered previously. Advances in generative machine-learning-based proposal samplers now enable efficient sampling in CV spaces of intermediate dimensionality—tens to hundreds of variables—and our results extend their applicability toward more realistic molecular systems.