3-CENTER HYDROGEN-BONDS IN DNA - MOLECULAR-DYNAMICS OF POLY(DA).POLY(DT)

The program AMBER 3.0 has been used to generate molecular trajectories of several models of dA-dT oligomers. The simulations were done without explicit solvent molecules but with two different dielectric functions (epsilon(r) = 4r and a sigmoidal distance-dependent dielectric function epsilon(r) = epsilon-cal). Best comparisons between experimental data based on Raman, NMR, and X-ray studies and calculated results are obtained with epsilon(r) = epsilon-cal. A comparative survey of the behaviors of the Watson-Crick and three-center hydrogen bonds was made to evaluate the importance of such hydrogen-bond systems in the stability of dA-dT sequences. Depending on the dielectric function, the lifetimes of the Watson-Crick H-bonds are 10 to 50 times longer than those of the three-center H-bonds in the major groove of dA-dT. The activation energies relevant for the three-center H-bonds are of the same order of magnitude as those underlying the pseudorotational movements of the puckered deoxyribose sugars (< 1 kcal mol-1). Despite mean lifetimes and activation energies for the three-center hydrogen bonds of the same order of magnitude value of 0.5, indicating a high probability of occurrence. Thus, three-center hydrogen bonds appear more as geometrical consequences of the anomalous structures adopted by dA-dT homopolymers (high propeller twist and low roll angles) than as structurally governing factors.