Molecular Dynamics Simulations of Dna Dimers Based on Replica-Exchange Umbrella Sampling Ii: Free Energy Analysis

The free energy change of the stacking process of DNA dimers has been investigated by potential of mean force (PMF) calculations. Two reaction coordinates were considered. One is the distance R between the glycosidic nitrogen atoms of the bases. The other is the pseudo dihedral angle X (N–Cl′–Cl′–N) . All 16 possible DNA dimers composed of the adenine, cytosine, guanine, or thymine bases in 5′ and 3′ positions were considered. 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 good agreement with the experimental results. We also observed that the PMF is the lowest at R = 4.0~4.4 Å and X = 20~40° for all the DNA dimers except for the dGpdA dimer. These values are close to those of the canonical B-DNA (4.4 Å and 29°).