Enhanced conformational space exploration for biomolecules using denoising diffusion probabilistic models

A central aspect of biomolecular simulations involves exploring molecular conformations reliably. This remains challenging, because conformational changes occur on timescales beyond current simulation tools. To address this, many approaches have emerged to cross relevant free-energy barriers by enhancing phase space sampling. One such technique is replica exchange molecular dynamics (REMD): several replicas run in parallel at different temperatures, periodically swapping configurations. High-temperature replicas help low-temperature replicas cross potential energy barriers, accelerating sampling at the target temperature.