Water-mediated tautomerization of cytosine to the rare imino form: An ab initio dynamics study

Abstract

Tautomerism in nucleotide bases is one of the possible mechanisms of mutation of DNA. In spite of numerous studies on the structure and energy of cytosine tautomers, little information is available on the process of proton transfer itself. We present here Born–Oppenheimer dynamics calculations, with the potential surface obtained “on the fly” from ab initio quantum chemistry (QC) and the atoms moving classically. In search for water-mediated tautomerization the monohydrated complex was studied, running about 300 trajectories each of 3000–5000 points of 1 fs steps. One single trajectory has been found to lead to tautomerization. Although the QC method used in the simulations was inevitably modest (B3LYP/3-21G), higher-level test calculations along the same trajectory suggest that the simulation grasped the basic mechanism of proton transfer: a concerted, synchronous process characterized by strong coupling between the motions of the two participating hydrogen atoms.