On the use of the adiabatic molecular dynamics technique in the calculation of free energy profiles

Abstract

A new molecular dynamics method for calculating free energy profiles for rare events is presented. The new method is based on the creation of an adiabatic separation between a reaction coordinate subspace and the remaining degrees of freedom within a molecular dynamics run. This is achieved by associating with the reaction coordinate(s) a high temperature and large mass, thereby allowing the activated process to occur while permitting the remaining degrees of freedom to respond adiabatically. In this limit, by applying a formal multiple time scale Liouville operator factorization, it can be rigorously shown that the free energy profile is obtained directly from the probability distribution of the reaction coordinate subspace and, therefore, no unbiasing of the configuration space or postprocessing of the output data is required. The new method is applied to a variety of model problems including a two-dimensional free energy surface and its performance tested against free energy calculations using the “blue moon ensemble” approach. The comparison shows that free energy profiles can be calculated with greater ease and efficiency using the new method.