Abstract
For the first time, in this study with the use of QM/QTAIM methods we have exhaustively investigated the tautomerization of the biologically-important conformers of the G*·C* DNA base pair—reverse Löwdin G*·C*(rWC), Hoogsteen G*′·C*(H), and reverse Hoogsteen G*′·C*(rH) DNA base pairs—via the single (SPT) or double (DPT) proton transfer along the neighboring intermolecular H-bonds. These tautomeric reactions finally lead to the formation of the novel G·(rWC), C(rWC), G*′N2·C(rWC), C(H), and G*′N7·C(rH) DNA base mispairs. Gibbs free energies of activation for these reactions are within the range 3.64–31.65 kcal·mol−1 in vacuum under normal conditions. All TSs are planar structures (Cs symmetry) with a single exception—the essentially non-planar transition state TSG*·C*(rWC)↔G+·C−(rWC) (C1 symmetry). Analysis of the kinetic parameters of the considered tautomerization reactions indicates that in reality only the reverse Hoogsteen G*′·C*(rH) base pair undergoes tautomerization. However, the population of its tautomerised state G*′N7·C(rH) amounts to an insignificant value−2.3·10−17. So, the G*·C*(rWC), G*′·C*(H), and G*′·C*(rH) base pairs possess a permanent tautomeric status, which does not depend on proton mobility along the neighboring H-bonds. The investigated tautomerization processes were analyzed in details by applying the author's unique methodology—sweeps of the main physical and chemical parameters along the intrinsic reaction coordinate (IRC). In general, the obtained data demonstrate the tautomeric mobility and diversity of the G*·C* DNA base pair.
Highlights
The study of the tautomerization mechanisms of the hydrogen (H) bonded nucleotide base pair is an important topic of modern quantum biophysics, biochemistry, molecular, and structural biology (Sinden, 1994; Sponer and Lankas, 2006; Alkorta et al, 2018)
In this study with the use of QM/quantum theory of Atoms in Molecules (QTAIM) methods we have exhaustively investigated the tautomerization of the biologically-important conformers of the G∗ · C∗ DNA base pair—reverse Löwdin G∗ · C∗(rWC), Hoogsteen G∗′ · C∗(H), and reverse Hoogsteen G∗′ · C∗(rH) DNA base pairs—via the single (SPT) or double (DPT) proton transfer along the neighboring intermolecular H-bonds
(Brovarets’ et al, 2017; Brovarets’ and Hovorun, 2019a) base mispairs and protein-DNA complexes (Brovarets’ et al, 2012), which we have summarized in our review (Brovarets’ and Hovorun, 2019b), devoted to the microstructural mechanisms of the tautomerization by the proton transfer along the neighboring intermolecular H-bonds in 22 biologically important pairs of nucleotide bases in the framework of the author’s method, which enable to trace the evolution of the physico-chemical parameters along the intrinsic reaction coordinate (IRC)
Summary
The study of the tautomerization mechanisms of the hydrogen (H) bonded nucleotide base pair is an important topic of modern quantum biophysics, biochemistry, molecular, and structural biology (Sinden, 1994; Sponer and Lankas, 2006; Alkorta et al, 2018). For over 65 years, this area of research has been under the intense scrutiny of both theoretics and experimentators, since the establishment of the spatial organization of DNA and formulation of the so-called “tautomeric hypothesis of the origin of spontaneous point mutations (transitions and transversions)” (Watson and Crick, 1953a,b; Erdmann et al, 2014) for this biologically important macromolecule—carrier of the genetic information, which is transmitted from generation to generation. This tautomeric hypothesis has been experiencing an era of renaissance (Brovarets’ and Hovorun, 2018). This problem is considered more complex with the involvement of several biologically important conformers of these pairs (Hoogsteen, 1963; Pous et al, 2008; Alvey et al, 2014; Brovarets’ and Hovorun, 2014a,b; Nikolova et al, 2014; Acosta-Reyes et al, 2015; Poltev et al, 2016; Zhou, 2016; Szabat and Kierzek, 2017; Ye et al, 2017)
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