Introduction

Replica-Exchange Molecular Dynamics (REMD) enhances sampling of binding and unbinding events by running many simulations in parallel, each with a different value for a specific variable, and attempting to exchange configurations between simulations with neighboring values periodically.

In REMD a group of simulations or replicas with different values for one variable (for instance, temperature or potential energy) is run in parallel and exchange in configurations is attempted periodically between replicas with neighboring values. Exchanges are accepted according to the Metropolis criterion. The exchange between replicas increases the chances that the simulation with standard parameters will sample a rare configuration or event. The values chosen for the variable must lead to enhanced sampling compared to standard parameters (for instance, increased temperature or smoothed potential energy). The number of replicas must be chosen to allow some superposition between the potential energy basins of replicas with neighboring values, in order to get reasonable chances of occurrence of swap of configurations. The use of the Metropolis criterion to exchange replicas ensures that detailed balance is achieved and that the exchange process will result in an equilibrium distribution.