DPT tautomerisation of the G·Asynand A*·G*synDNA mismatches: a QM/QTAIM combined atomistic investigation

By applying a combined QM and QTAIM atomistic computational approach we have established for the first time that the G·A(syn) and A*·G*(syn) DNA mismatches (rare tautomers are marked with an asterisk), causing spontaneous transversions with substantially various probabilities, radically differ from each other in their ability to tautomerise through the double proton transfer (DPT). The A*·G*(syn) mismatch tautomerises quite easily (ΔΔG(TS) ≈ 4·kT at room temperature) into the A·G*(syn) mismatch through the asynchronous concerted mechanism, whereas the G·A(syn) base mispair does not tautomerise via the DPT at all, since there is no local minimum corresponding to the tautomerised G*·A*(syn) mismatch on the potential energy surface. It was established that the A·G*(syn) base mispair is a dynamically unstable H-bonded complex with an extremely short lifetime of 2.17 × 10(-13) s. Consequently, the obtained results allow us to believe that spontaneous or forced dissociation of both the G·A(syn) and A*·G*(syn) DNA mismatches by the DNA-polymerase occurs with the preservation of the tautomeric status of the bases.