Novel pathway for mutagenic tautomerization of classical ??? DNA base pairs via sequential proton transfer through quasi-orthogonal transition states: A QM/QTAIM investigation.

ABSTRACT: In this paper we have theoretically predicted a novel pathway for the mutagenic tautomerization of the classical A?T DNA base pairs in the free state, the Watson-Crick A·?(WC), reverse Watson-Crick A·?(rWC), Hoogsteen A·?(H) and reverse Hoogsteen A·?(rH) pairs, via sequential proton transfer accompanied by a significant change in the mutual orientation of the bases. Quantum-mechanical (QM) calculations were performed at the MP2/aug-cc-pVDZ//B3LYP/6-311++G(d,p) level in vacuum phase, along with Bader's quantum theory of Atoms in Molecules (QTAIM). These processes involve transition states (TSs) with quasi-orthogonal structures (symmetry C1), which are highly polar, tight ion pairs (A-, N6H2-deprotonated)?(T+, O4/O2-protonated). Gibbs free energies of activation for the A?T(WC) / A?T(rWC) ? A*??(rwWC) / A*??(wWC) tautomeric transitions (~43.5 kcal?mol-1) are lower than for the A?T(H) / A?T(rH) ? A*N7??(rwH) / A*N7??(wH) tautomerisations (~53.0 kcal?mol-1) (rare tautomers are marked by an asterisk; w-wobble configured tautomerisation products). The (T)N3+H?N1-(A), (T)O4+H?N1-(A) / (T)N3+H?N1-(A) and (T)O2+H?N1-(A) H-bonds are found in the transition states TSA-·T+A·T(WC)?A*·T(rwWC) / TSA-·T+A·T(rWC)?A*·T(wWC). However, in the transition state TSA-·T+A·?(H)?A*N7·T(rwH) / TSA-·T+A·?(rH)?A*N7·T(wH), the (T)N3+H?N7-(A), (T)O4+H?N7-(A) / (T)N3+H?N7-(A) and (T)O2+H?N7-(A) H-bonds are supplemented by the attractive (T)O4+/O2+?N6-(A) van der Waals contacts. It was demonstrated that the products of the tautomerization of the classical A?T DNA base pairs-A*??(rwWC), A*N7??(rwH) and A*N7??(wH) (symmetry Cs)-further transform via double proton transfer into the energetically favorable wobble A?T*(rwWC), A?T*(rwH) and A?T*O2(wH) base mispairs (symmetry Cs).

SUBMITTER: Brovarets' OO 

PROVIDER: S-EPMC6021055 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature