Kinetic Study of Transition Mutations from G-C to A-T Base Pairs in Watson-Crick DNA Base Pairs: Double Proton Transfers.

According to the Löwdin model [ Rev. Mod. Phys. 1963, 35, 724-732], the Watson-Crick guanine-cytosine (G-C) base pair is tautomerized (G*-C*) with a small probability and then replication of G*-C* produces G*-thymine (T) and adenine (A)-C* base pairs. On the basis of this model and our previous work [ J. Phys. Chem. B 2020, 124, 1715-1722], we first calculated the intrinsic reaction coordinates from G*-T to G-T* using density functional theory and evaluated the probability of G*-T tautomerization to G-T* by double proton transfer (DPT) on the basis of the transition state theory. Similarly, we calculated the probability of A-C* tautomerization to A*-C by DPT. Then, according to these probabilities, we calculated the probability of transition mutations from G-C to A-T after 2 replications. The calculated probability was 1.31 × 10-8, a value consistent with the mutation rate previously reported by Drake et al. [ Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 7160-7164]. Our results suggest that DPT is one cause of the G-C → A-T transition. To investigate differences in the optical properties between G*-T and G-T* and between A-C* and A*-C, we also evaluated the infrared absorption spectra and Raman intensities for these base pairs.