In the present work, we investigate the double proton transfer (DPT) tautomerization process in Guanine-Cytosine (GC) DNA base pairs. In particular, we study the influence of the biological environment on the mechanism, the kinetics and thermodynamics of such DPT. To this end, we present a molecular dynamics (MD) study in the tight-binding density functional theory framework, and compare the reactivity of the isolated GC dimer with that of the same dimer embedded in a small DNA structure. The impact of nuclear quantum effects (NQEs) is also evaluated using Path Integral based MD. Results show that in the isolated dimer, the DPT occurs via a concerted mechanism, while in the model biological environment, it turns into a step-wise process going through an intermediate structure. One of the water molecules in the vicinity of the proton transfer sites plays an important role as it changes H-bond pat- tern during the DPT reaction. The inclusion of NQEs has the effect of speeding up the tautomeric-to-canonical reaction, reflecting the destabilization of both the tautomeric and intermediate forms.
In the supporting information we report: (1) Details on DFTB benchmarking; (2) Details of reaction dynamics and Umbrella sampling simulations; (3) Additional results in terms of population decays, 16-beads results, distance distributions and direct dynamics trajectories with 5 base pairs, smaller time step and crystallographic water molecules around the isolated base pair. Details on the charge calculation procedure are also provided with the corresponding results.
A movie file showing a prototypical reaction.