A Kinetic Approach to Double Proton Transfer in Watson–Crick DNA Base Pairs

Abstract

Double proton transfer (DPT) in guanine-cytosine (GC) base pairs and adenine-thymine (AT) base pairs produces tautomeric forms, denoted G*C* and A*T*. To examine DPT, (i) intrinsic reaction coordinates for DPT, (ii) probabilities of change from GC to G*C* and from AT to A*T*, and (iii) infrared absorption intensities of GC and G*C* were investigated on the basis of density functional theory and Eyring’s chemical kinetics. The probabilities of change from GC to G*C* were 3 × 10–8, and those from AT to A*T* were 2 × 10–10. These values are consistent with the rate of mutation previously reported by Drake et al. (Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 7160–7164). G*C* exhibited two vibrational modes around 3000 cm–1, whereas GC exhibited no vibrational modes around the same frequency. The infrared intensity calculated for G*C* showed that the strong absorption obtained around 3000 cm–1 was caused by one of the two modes.

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

“…Then, we assumed the following reversible first-order reaction equation as the reaction scheme shown in eq where [R] t and [P] t are the concentrations of the reactant and product at time t , respectively. The rate constants are expressed as follows according to refs , , and . where α = f or r represents forward or reverse reaction, respectively. k B represents the Boltzmann’s constant, and T is the absolute temperature.…”

“…Z TS ‡ denotes the partition function of the transition state, and Z f and Z r are the partition functions of the reactant and product, respectively. The latter 2 partition functions are based on quantum statistical mechanics . These 3 partition functions do not consider the translational and rotational motions because base pairs are assumed to be present in the DNA double helix.…”

“…The tunneling factor for G–C → G*–C* tautomerization was recalculated using the Eckert potential to be consistent with the G*–T → G–T* and A–C* → A*–C tautomerizations. (In ref , it was evaluated using the Wigner correction, and its value was κ W = 3.54). The calculated value using eq was κ = 3.30 at T = 300 K.…”

“…Based on that model, base pairs appearing after replicating twice from G–C are represented as shown in Figure . G–C in the upper left of Figure changes to G*–C* by DPT with a probability of approximately 10 –8 . Then, G*–C* is replicated.…”

“…In our previous paper, (i) we used density functional theory (DFT) to determine the intrinsic reaction coordinate (IRC) from G–C to G*–C* via the transition state. Similarly, we used DFT to determine the IRC from A–T tautomerization to A*–T* via the transition state.…”