title: Atomistic understanding of the C·T mismatched DNA base pair tautomerization via the DPT: QM and QTAIM computational approaches.
abstract: 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 (ΔG(int) = -1.54 kcal mol(-1) ) and even slightly more stable than the A·T Watson-Crick DNA base pair (ΔG(int) = -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 TS(C·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 TS(C·T ↔ C*·T*) stabilized by the loosened N4-H-O4 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.
authors: Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Zabolotnoho Str., Kyiv, 03680, Ukraine; Research and Educational Center, State Key Laboratory of Molecular and Cell Biology, 150 Zabolotnoho Str., Kyiv, 03680, Ukraine; Department of Molecular Biotechnology and Bioinformatics, Institute of High Technologies, Taras Shevchenko National University of Kyiv, 2 Hlushkova Ave., Kyiv, 03022, Ukraine.
authors: Ol'ha O
authors: OO
authors: Brovarets'
authors: Dmytro M
authors: DM
authors: Hovorun
mesh_terms: D020137:Base Pair Mismatch; D020029:Base Pairing; D003596:Cytosine / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D011522:Protons; D011789:Quantum Theory; D013816:Thermodynamics; D013941:Thymine / Q000737:chemistry*
chemical_list: D011522:Protons; D003596:Cytosine; D004247:DNA; D013941:Thymine
keywords: B3LYP and MP2 levels of QM theory; QTAIM analysis ·Grunenberg's compliance constant; amino and imino tautomers of cytosine; cooperativity of the H-bonds; keto and enol tautomers of thymine; mutagenic tautomerization; spontaneous point mutations in DNA; sweeps of the energetic, electron-topological, geometric and polar parameters along the IRC; the double proton transfer; van der Waals contact