Theoretical investigation of the proton transfer mechanism in guanine-cytosine and adenine-thymine base pairs.

Ab initio constrained molecular dynamics and metadynamics were employed to investigate the mechanism of proton transfer in guanine-cytosine (GC) and adenine-thymine (AT) base pairs in the gas phase at room temperature. It is shown that double proton transfer (DPT) in the GC base pair is a concerted and asynchronous mechanism, and three pathways with a similar free energy barrier start from the canonical GC and end up in its "rare" imino-enol tautomer. The activation energy for the route that the DPT starts from the hydrogen atom movement in the O6(G)-N4(C) bridge is approximately 1.0 kcal/mol higher than that which starts in the N1(G)-N3(C) bridge. For the AT base pair, a stable intermediate state is identified in the two-dimensional free energy surface of the DPT event. We found that the movement of the hydrogen atom in the N1(A)-N3(T) bridge occurs before the movement of the hydrogen atom in the N6(A)-O4(T) bridge. Thus, it is demonstrated that the DPT in AT base pairs is a stepwise and an asynchronous mechanism.