Free energy calculations for DNA base stacking by replica-exchange umbrella sampling

We have investigated the free energy change of the stacking process of DNA dimers using molecular dynamics simulations based on replica-exchange umbrella sampling. Pairs of replicas with different umbrella potentials are exchanged in this method, which allows the simulation to sample much wider conformational space and, therefore, to yield more accurate free energy profiles than by the conventional umbrella sampling. From the free energy profiles, we observed good stacking for all DNA dimers and sequence-dependent stacking stability. This sequence dependence of the stacking free energy is in accord with the experimental results. (C) 2003 Elsevier B.V. All rights reserved.