Reaching biological timescales with all-atom molecular dynamics simulations

Molecular dynamics (MD) simulations can provide atomically detailed views of protein motions, sampling multiple timescales ranging from femtoseconds to nanoseconds on typical computing resources. The ‘reach’ of these computer simulations toward biologically relevant timescales (microseconds and beyond) has been improving with advances in hardware and software, as well as the development of enhanced sampling techniques. This review outlines these advances, focusing on techniques that also provide realistic, unperturbed kinetics. These longer-timescale MD simulations can provide detailed insights into the mechanisms of biological events, potentially aiding the design of pharmaceuticals.