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By how many tautomerisation routes the Watson–Crick-like A·C* DNA base mispair is linked with the wobble mismatches? A QM/QTAIM vision from a biological point of view

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Abstract

Here for the first time we present four novel routes of the tautomerisation via the sequential DPT that links biologically important A·C*(WC) DNA base mispair with Watson–Crick (WC) geometry and wobble (w) A*·C*(w), A·C*O2(w), A*·C*(w 1) and A·C(w ⊥) mismatches, pursuing the goal of estimation of their contribution into the transition mutations during DNA biosynthesis. These processes occur without opening of the pairs and are accompanied by the substantial changes in their geometry. A detailed analysis of these pathways leads to an identification of the A·C*(WC)↔A*·C*(w) tautomerisation route as the most suitable among these processes from the point of view of the spontaneous point mutagenesis, since it proceeds via the time that is significantly less than the time used by the replicative DNA-polymerase for the incorporation of one incoming nucleotide into the synthesised DNA double helix. This non-dissociative transition occurs through the planar, highly stable, zwitterionic \( {\text{TS}}_{{{\text{A}} \cdot {\text{C*(WC)}} \leftrightarrow {\text{A}}^{ + } \cdot {\text{C}}^{\text{ - }} (w )}}^{{{\text{A}}^{ + } \cdot {\text{C}}^{\text{ - }} }} \) transition state and dynamically unstable intermediate A+·C−(w) ion pair and is accompanied by the consistent rearrangement of the 10 unique patterns of the specific intermolecular interactions, among which there are from 2 to 4 AH···B H-bonds and 2 loosened A–H–B covalent bridges. Basic physico-chemical properties of this mutual tautomeric transformation, which is internally inherent to the A·C*(WC) and A*·C*(w) base mispairs, are documented, and its possible biological assignment is discussed here.

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Acknowledgments

O.O.B. was supported by the Grant of the President of Ukraine to support scientific research of young scientists for 2015 year from the State Fund for Fundamental Research of Ukraine (Project No. GP/F61/028), by the Grant of the NAS of Ukraine for young scientists for the years 2015–2016 and by the Scholarship of the President of Ukraine for young scientists for the years 2014–2016 given to O.O.B. This work was performed using computational facilities of joint computer cluster of SSI “Institute for Single Crystals” of the National Academy of Sciences of Ukraine and Institute for Scintillation Materials of the National Academy of Sciences of Ukraine incorporated into Ukrainian National Grid. The authors sincerely thank Dr. Ivan S. Voiteshenko (Institute of High Technologies, Taras Shevchenko National University of Kyiv) and Dr. Fernando R. Clemente (Gaussian, Inc.) for their technical support of the work.

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  1. Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Akademika Zabolotnoho Str., Kyiv, 03680, Ukraine

    Ol’ha O. Brovarets’ & Dmytro M. Hovorun

  2. Department of Molecular Biotechnology and Bioinformatics, Institute of High Technologies, Taras Shevchenko National University of Kyiv, 2-h Akademika Hlushkova Ave., Kyiv, 03022, Ukraine

    Ol’ha O. Brovarets’ & Dmytro M. Hovorun

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This paper is dedicated to outstanding Ukrainian Scientist Dr. Sci. Oleg Shishkin, who made a great contribution into the development of quantum chemistry in Ukraine and left a prominent scientific heritage.

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Brovarets’, O.O., Hovorun, D.M. By how many tautomerisation routes the Watson–Crick-like A·C* DNA base mispair is linked with the wobble mismatches? A QM/QTAIM vision from a biological point of view. Struct Chem 27, 119–131 (2016). https://doi.org/10.1007/s11224-015-0687-4

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