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.