PM6 quantum chemical study of the H-bonded and stacked associates of the adenine and thymine DNA bases: The nature of base stacking

Abstract

The planar H-bonded adenine-thymine (A • T) base pair and four stacked hetero associates (A/T) of these bases in a cluster containing 200 water molecules were studied by the new semi-empirical PM6 method. The formation of the planar A • T base pair in the water cluster was found to be energetically unfavourable, primarily due to the destabilising contribution of the base-water interactions. Under complete geometry optimisation, the planar A • T base pair converted into a nonplanar propeller-twisted and buckled associate. In contrast, the formation of all stacked dimers studied was found to be favourable, with formation energies ranging from −11 to −20 kcal/mol. The preference for the formation of these stacks results from the favourable change in the water structure and distortion of the paired and isolated bases during the base association reaction.

Keywords:

• adenine-thymine
• base pair
• base stacking
• PM6

Acknowledgements

One of us (VID) is grateful to Professor J.J.P. Stewart for helpful discussions on the PM6 method and for additional output data, and to Professor A. Ben-Naim for helpful discussions on the hydration of biomolecules and for copies of his publications. TvM gratefully acknowledges the Royal Society for their support under the University Research Fellowship scheme.