From Metadynamics to Dynamics

Pratyush Tiwary, Michele Parrinello

Published 2013-09-20, updated 2013-12-05Version 2

Metadynamics is a commonly used and successful enhanced sampling method. By the introduction of a history dependent bias which depends on a restricted number of collective variables(CVs) it can explore complex free energy surfaces characterized by several metastable states separated by large free energy barriers. Here we extend its scope by introducing a simple yet powerful method for calculating the rates of transition between different metastable states. The method does not rely on a previous knowledge of the transition states or reaction co-ordinates, as long as CVs are known that can distinguish between the various stable minima in free energy space. We demonstrate that our method recovers the correct escape rates out of these stable states and also preserves the correct sequence of state-to-state transitions, with minimal extra computational effort needed over ordinary metadynamics. We apply the formalism to three different problems and in each case find excellent agreement with the results of long unbiased molecular dynamics runs.