Guanine−Cytosine Base Pairs in Parallel-Stranded DNA:  An ab Initio Study of the Keto−Amino Wobble Pair versus the Enol−Imino Minor Tautomer Pair

Doubly hydrogen bonded, “reverse Watson−Crick” thymine−adenine base pairs make possible the formation of parallel-stranded DNA double helices. Although the presence of guanine and cytosine reduces the stability of parallel-stranded DNA, the rather modest experimentally determined reduction in stability (less than 1 kcal/mol for each C−G pair) has been ascribed separately to favorable amino−amino contacts, tautomerizations, and a wobble pair geometry. Earlier studies predicted that favorable amino−amino contacts could yield an interaction energy (gas phase) of about −5 kcal/mol for a twisted, reverse Watson−Crick C−G base pair. It is shown here that either a minor tautomer pairing or a wobble pairing can much more strongly stabilize reversed C−G base pairs. The calculated gas-phase interaction energies of −14 kcal/mol each are comparable to the gas-phase stability of a T−A base pair. Aqueous-phase calculations, however, greatly favor the wobble pair geometry by 9 kcal/mol.