Enhanced Sampling on Domain/Motif Level with Kinetic Accelerated Molecular Dynamics

Abstract

Molecular dynamics (MD) has become a popular simulation tool in recent years. However, its application is often limited by a timescale problem, due to its femtosecond-level integration timestep. To address this challenge, various enhanced sampling methods have been developed to accelerate system dynamics. Here, we introduce a novel enhanced sampling approach: Kinetically Accelerated Molecular Dynamics (KAMD). By combining the atomic-level accuracy of MD with the diffusive behavior of Brownian dynamics (BD), KAMD significantly improves sampling efficiency on domain/motif level while preserving equilibrium properties. We showed that KAMD is particularly effective in simulating two types of processes: large-scale conformational changes and ligand unbinding events.