Adaptive sampling for rare-event kinetics

Adaptive sampling methods are becoming increasingly popular for speeding up rare events in simulation such as molecular dynamics (MD) without biasing the system dynamics. Several adaptive sampling strategies have been proposed, but it is not clear which methods perform better for different physical systems.
We present a systematic evaluation of selected adaptive sampling strategies on a wide selection of fast-folding proteins using models constructed on previously simulated MD trajectories. We provide theoretical limits for the sampling speedup and compare the performance of different strategies with and without using some a priori knowledge of the system. Interestingly, the maximum speedup achievable for the adaptive sampling of slow processes increases for proteins with longer folding times, encouraging the application of these methods for the characterization of slower processes.