Molecular dynamics simulations of DNA dimers based on replica-exchange umbrella sampling. I. Test of sampling efficiency

In order to elucidate the stacking-unstacking process of DNA dimers, we have performed molecular dynamics simulations based on replica-exchange umbrella sampling (REUS), which is one of powerful conformational sampling techniques. We studied four DNA dimers composed of the adenine and thymine bases in both the 5' and the 3' positions (dApdA, dApdT, dTpdA, and dTpdT). We examined the time series of the distance between the glycosidic nitrogen atoms, root-mean-square deviations from A-DNA and B-DNA, various backbone and glycosidic torsion angles, and the pseudorotation phase angles as functions of the simulation time step. All these time series imply that the present simulation has indeed sampled a very wide conformational space. The results for the backbone and glycosidic torsion angles and pseudorotation phase angles imply that B-DNA structures are the dominant motif of the stacked dimers, while a small population of A-DNA also exists in the stacked states.