Potential Energy and Free Energy Surfaces of All Ten Canonical and Methylated Nucleic Acid Base Pairs:  Molecular Dynamics and Quantum Chemical ab Initio Studies

Abstract

The potential energy surfaces (PESs) and free energy surfaces (FESs) of all 10 canonical and methylated nucleic acid base pairs were studied by a molecular dynamics/quenching (MD/Q) technique with the Cornell et al. empirical force field and by a correlated ab initio quantum chemical method. More than a dozen energy minima were located on the PES of each base pair. The global and first local minima of nonmethylated base pairs have a systematically planar H-bonded structure, while T-shaped and stacked structures are less stable. The MD/Q search sometimes reveals an unexpected structure as the global energy minimum (e.g., the global minimum of the adenine...thymine PES corresponds neither to the Watson−Crick nor the Hoogsteen type of bonding). Entropy does not play an important role and the relative order of individual structures on the PES and FES does not differ too much. Methylation at purine N9 and pyrimidine N1 brings dramatic changes in the PESs and FESs, mainly because the most stable and most popula...