Kinetic Study of Transition Mutations from G–C to A–T Base Pairs in Watson–Crick DNA Base Pairs: Double Proton Transfers
Kei Odai, Keisho Umesaki
Abstract
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.