The nature of the transition mismatches with Watson-Crick architecture: the G*•T or G•T* DNA base mispair or both? A QM/QTAIM perspective for the biological problem

This study provides the first accurate investigation of the tautomerization of the biologically important guanine*center dot thymine (G*center dot T) DNA base mispair with Watson-Crick geometry, involving the enol mutagenic tautomer of the G and the keto tautomer of the T, into the G center dot T* mispair ( increment G = .99 kcal mol(-1), population = 15.8% obtained at the MP2 level of quantum-mechanical theory in the continuum with epsilon = 4), formed by the keto tautomer of the G and the enol mutagenic tautomer of the T base, using DFT and MP2 methods in vacuum and in the weakly polar medium (epsilon = 4), characteristic for the hydrophobic interfaces of specific protein-nucleic acid interactions. We were first able to show that the G*center dot T <-> G center dot T* tautomerization occurs through the asynchronous concerted double proton transfer along two antiparallel O6H center dot center dot center dot O4 and N1 center dot center dot center dot HN3 H-bonds and is assisted by the third N2H center dot center dot center dot O2 H-bond, that exists along the entire reaction pathway. The obtained results indicate that the G center dot T* base mispair is stable from the thermodynamic point of view complex, while it is dynamically unstable structure in vacuum and dynamically stable structure in the continuum with epsilon = 4 with lifetime of 6.4 center dot 10(-12) s, that, on the one side, makes it possible to develop all six low-frequency intermolecular vibrations, but, on the other side, it is by three orders less than the time (several ns) required for the replication machinery to forcibly dissociate a base pair into the monomers during DNA replication. One of the more significant findings to emerge from this study is that the short-lived G center dot T* base mispair, which electronic interaction energy between the bases (-23.76 kcal mol(-1)) exceeds the analogical value for the G center dot C Watson-Crick nucleobase pair (-20.38 kcal mol(-1)), escapes from the hands of the DNA replication machinery by fast transforming into the G*center dot T mismatch playing an indirect role of its supplier during the DNA replication. So, exactly the G*center dot T mismatch was established to play the crucial role in the spontaneous point mutagenesis.