Nucleic acid constituent interactions

Abstract

Hydrogen bonding contributes of the order of 5–15 kcal/mol base pair to the stability of the helix (electronic or intrinsic energy). This contribution is selective, i.e., there is a preferential stability of the Watson-Crick G-C pair relative to all other pairs. Stacking interactions contribute approximately of the same order as hydrogen bonding. Perhaps the most interesting aspect of the stacking interactions which emerges from the theoretical analysis is the fact that the stacking maxima are not necessarily at the angles the successive base pair plans assume in a regular double helix. Consequently some sequence dependent structure peculiarities may arise. That is, the double helix may have a fine structure contingent on the sequence of base pairs. Indeed such sequence dependent polymorphism has been reported in the recent literature and appears to influence the ability of aromatic drugs to intercalate into the helix. The solvent effect which is another factor of stability seems to decrease somewhat bonding scheme preferences. For example, in the model we used to estimate solvent effect, we find that the G-C pair formation is de-stabilized strongly in water, while the A-T pair formation is mildly enhanced. The continuum model of solvent effect leads to similar qualitative conclusions. Studies of backbone conformation indicate that only a limited range of conformational states are comparable with the helical configuration. Improved empirical methods are needed in order to successfully calculate backbone effects for relatively large segments of nucleic acids.