Contribution of the phosphodiester backbone and glycosyl linkage intrinsic torsional energetics to DNA structure and dynamics

The intrinsic conformational energetics of macromolecules are an important contribution to their structure and dynamics. This information, however, is lacking for most dihedrals about rotatable bonds in nucleic acids. To bridge this gap, high-level ab initio quantum mechanical calculations have been performed on a number of furanose-based model compounds designed to model the intrinsic torsional energetics of the dihedrals epsilon, gamma, beta, and chi in deoxyribonucleic acid (DNA). Energy profiles have been obtained with furanose in both the C3' endo and C2' endo conformations, to model the torsions in the context of the two conformational ranges populated by the sugar in DNA. The resulting energy profiles are compared to the corresponding crystallographically determined population distributions, with which they can be reconciled to a large extent. This suggests that the models used to derive these energy surfaces are relevant to DNA. Torsion epsilon is found to be intrinsically very flexible with the low-energy regions encompassing the B-I and B-II substates. The Br internal energy is found to be on the order of 1.5 kcal/mol more stable than the B-I conformation. The torsional energy barrier between B-I and B-II is relatively low, on the order of 2.1 kcal/mol. Estimates of other torsional energy barriers suggest that the paths of lowest energy between gamma = g(+) and gamma = g(-) and between the ii anti and syn orientations are through gamma = 0 degrees and gamma = 120 degrees, respectively. The chi energy surfaces offer insights into the contribution of base-furanose interactions to the corresponding distributions in DNA and its components, in terms of purines versus pyrimidines, and point to the unique properties of cytosine. These surfaces also indicate that a syn base interacts more favorably with a north furanose than with a south furanose, in contrast with a widely accepted view.