Atomistic understanding of the C·T mismatched DNA base pair tautomerization via the DPT: QM and QTAIM computational approaches
Article first published online: 16 AUG 2013
Copyright © 2013 Wiley Periodicals, Inc.
Journal of Computational Chemistry
Volume 34, Issue 30, pages 2577–2590, 15 November 2013
How to Cite
How to cite this article: J. Comput. Chem. 2013, 34, 2577–2590. DOI: 10.1002/jcc.23412, .
- Issue published online: 10 OCT 2013
- Article first published online: 16 AUG 2013
- Manuscript Accepted: 25 JUL 2013
- Manuscript Received: 17 JUN 2013
- State Fund for Fundamental Research of Ukraine (project no. GP/F56/074; Grant of the President of Ukraine)
- Ministry of Education and Science, Youth and Sports of Ukraine (Grant of the President of Ukraine)
- spontaneous point mutations in DNA;
- amino and imino tautomers of cytosine;
- keto and enol tautomers of thymine;
- mutagenic tautomerization;
- sweeps of the energetic, electron-topological, geometric and polar parameters along the IRC;
- the double proton transfer;
- cooperativity of the H-bonds;
- van der Waals contact;
- B3LYP and MP2 levels of QM theory;
- QTAIM analysis ·Grunenberg's compliance constant
It was established that the cytosine·thymine (C·T) mismatched DNA base pair with cis-oriented N1H glycosidic bonds has propeller-like structure (|N3C4C4N3| = 38.4°), which is stabilized by three specific intermolecular interactions–two antiparallel N4H…O4 (5.19 kcal mol−1) and N3H…N3 (6.33 kcal mol−1) H-bonds and a van der Waals (vdW) contact O2…O2 (0.32 kcal mol−1). The C·T base mispair is thermodynamically stable structure (ΔGint = −1.54 kcal mol−1) and even slightly more stable than the A·T Watson–Crick DNA base pair (ΔGint = −1.43 kcal mol−1) at the room temperature. It was shown that the C·T C*·T* tautomerization via the double proton transfer (DPT) is assisted by the O2…O2 vdW contact along the entire range of the intrinsic reaction coordinate (IRC). The positive value of the Grunenberg's compliance constants (31.186, 30.265, and 22.166 Å/mdyn for the C·T, C*·T*, and TSC·T C*·T*, respectively) proves that the O2…O2 vdW contact is a stabilizing interaction. Based on the sweeps of the H-bond energies, it was found that the N4H…O4/O4H…N4, and N3H…N3 H-bonds in the C·T and C*·T* base pairs are anticooperative and weaken each other, whereas the middle N3H…N3 H-bond and the O2…O2 vdW contact are cooperative and mutually reinforce each other. It was found that the tautomerization of the C·T base mispair through the DPT is concerted and asynchronous reaction that proceeds via the TSC·T C*·T* stabilized by the loosened N4HO4 covalent bridge, N3H…N3 H-bond (9.67 kcal mol−1) and O2…O2 vdW contact (0.41 kcal mol−1). The nine key points, describing the evolution of the C·T C*·T* tautomerization via the DPT, were detected and completely investigated along the IRC. The C*·T* mispair was revealed to be the dynamically unstable structure with a lifetime 2.13·× 10−13 s. In this case, as for the A·T Watson–Crick DNA base pair, activates the mechanism of the quantum protection of the C·T DNA base mispair from its spontaneous mutagenic tautomerization through the DPT. © 2013 Wiley Periodicals, Inc.