DPT tautomerisation of the G·Asyn and A*·G*syn DNA mismatches: a QM/QTAIM combined atomistic investigation

Abstract

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.