Quantum dancing of the wobble G•T(U/5BrU) nucleobase pairs and its biological roles

Abstract

This paper represents generalization of the novel tautomerization mechanism of the G•T/G•U nucleobase pairs – quantum transformation of the standard wobble G•T(w)/G•U(w) base pairs into the Watson–Crick-like (WC) structures: G•T(w)/G•U(w)→G•T*(WC)/G•U*(WC)→G*•T(WC)/G*•U(WC) (here * defines the mutagenic tautomeric state of the nucleobase) obtained at the MP2/6-311++G(2df,pd) // B3LYP/6-311++G(d,p) level of theory in vacuum (ε=1) and in the continuum with ε=4 under normal conditions. This transition proceeds through the transition state as a tight zwitterionic base pair – G+•T-/G+•U- (protonated guanine (G+) bounded with deprotonated thymine/uracil (T−/U−)). This tautomerization process occurs through the sequential proton transfer within the base pair followed by the shifting of the bases according each other. These data enable to understand the mechanism of the adaptation of the wobble G•T/G•U nucleobase pairs to the Watson–Crick-like geometry of the classical A•T(U)/G•C nucleobase pairs for the successful incorporation into the DNA/RNA duplex, leading to spontaneous point mutations. Based on this data it was reliably explained the origin of the spontaneous and induced by 5BrU molecule point mutations, in particular incorporation errors. It was also detected that the low-polar environment, which is characteristic for the interfaces of the biomolecular interactions, slows down these tautomerization processes due to the increasing of the energetical barriers. Finally, perspectives and ideas according further applications of this model have been provided. We sincerely believe that this investigation will give a significant boost to the development of the field of physical chemistry of nucleic acids, as well as related disciplines such as medicinal chemistry, health research, quantum biology, spectroscopy, crystallography and bioinformatics. This finding also allows to understand in more details the structure, dynamics and functions of DNA and RNA macromolecules by considering their quantum behavior.