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Novel Conformationally-Tautomeric Properties of the Biologically Important at DNA Base Pairs ("63rd Annual Meeting of the Biophysical Society BPS'2019"; https://www.biophysics.org/2019meeting#/; Baltimore, Maryland, USA, March 2-6, 2019)
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https://www.sciencedirect.com/science/article/abs/pii/S0006349518317119
"63rd Annual Meeting of the Biophysical Society BPS'2019" (Baltimore, Maryland, USA, March 2-6, 2019)
For the first time we have revealed at the MP2/aug-cc-pVDZ//B3LYP/6-311++G(d,p) level of theory the novel routes for the conformationally-tautomeric transitions for the four biologically important А∙Т DNA base pairs – Watson-Crick А∙Т(WC), reverse Watson-Crick А∙Т(rWC), Hoogsteen А∙Т(Н) and reverse Hoogsteen А∙Т(rН), in particular:
- Unconventional conformational states – А·Т(wWC), А·Т(wrWC), А·Т(wН) and А·Т(wrН), in which the amino group of the A DNA base acts simultaneously as a donor and an acceptor of the H-bonding [1];
- Non-dissociative conformational transitions – А∙Т(WC) / А∙Т(rWC)↔А∙Т(H) / А∙Т(rH), A∙T(WC)↔A∙T(rWC) / A∙T(rH) and A∙T(H)↔A∙T(rH) / A∙T(rWC), which link А∙Т DNA base pairs and their novel conformers in different combinations [2, 3];
- Novel pathways of the intrapair tautomerisation in the А∙Т DNA base pairs through the quasi-orthogonal transition state – А∙Т(WC) / А∙Т(rWC)↔А*∙Т(rwWC) / А*∙Т(wWC) and А∙Т(H) / А∙Т(rH)↔А*N7∙Т(rwH) / А*N7∙Т(wH) [4] – or through the protonated amino group of the A DNA base – A∙T(wWC)↔A∙T*(w⊥WC), A∙T(wrWC)↔A∙T*O2(w⊥rWC), A∙T(wH)↔A∙T*(w⊥H) and A∙T(wrH)↔A∙T*O2(w⊥rH) [5].
We have also established scientifically-based explanation, why Nature exploits exactly А∙Т(WC) DNA base pair for the construction of the genetic material [6].
The biophysical significance and experimental confirmation of the results are thoroughly discussed.
Acknowledgements. DrSci Ol’ha Brovarets’ expresses sincere gratitude to Biotech Initiative U.S.-Ukraine Foudation (USUF) for the travel grant (“2018 Emerging Biotech Leader of Ukraine”; https://www.usukraine.org/biotechnology-initiative/) for the participation in the 63rd Annual Meeting of the Biophysical Society BPS2019 (Baltimore, Maryland, March 2-6, 2019; https://www.biophysics.org/2019meeting#/).
Session: Posters: DNA Replication, Recombination, and Repair
Location: Exhibit Hall C
Date: Sunday, Mar 3 1:45 PM
Duration: 2 hours
Board Number: B152
https://plan.core-apps.com/bpsam2019/event/5ccb988de3973cc7e57859c3b400f6af
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... Topic of the prototropic tautomerism is of paramount importance nowadays [1][2][3][4][5][6][7][8][9][10][11][12][13], since, from the one side, attention in different areas of research [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] -drug design, physics of crystals, NMR spectroscopy, biologically important molecules etc. Point of view that in biological molecules tautomeric transformations are inseparable from the conformational transformations is becoming more and more popular [31][32][33][34][35]. This enables to open new possibilities for the understanding of the intimate mechanisms of the functioning of biomolecules in a living cell. ...
... Especial interest tautomerism represents for nucleic acids [36,37], since transfer of just one proton inside DNA or RNA base pair leads to the groundbreaking changes in their structure and functioning [3,[32][33][34][35][36] and is usually associated with mutagenic properties [38][39][40][41]. ...
This paper represents careful quantum-mechanical investigation with further generalization of the novel transformation mechanisms for the wobble G·T(wWC) and reverse wobble G·T(rwWC) base pairs into the classical Watson–Crick-like G*·T(WC) base pair, obtained at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory in vacuum under normal conditions (T = 298.15 K). These G·T(wWC)↔G·T*(WC)↔G*·T(WC), G·T(wWC)↔G·T*O2(rWC)↔G+·T−(rWC)↔G*·T(rWC)↔G*·T(WC), G·T(rwWC)↔G*·T(rWC)↔G*·T(WC) and G·T(rwWC)↔G·T*(WC)↔G*·T(WC) conformationally-tautomeric reactions are determined by the sequential proton transfer inside the base pair, shifting of the G and T DNA bases relatively each other and cis↔trans changing of their mutual orientation. The main intrigue of the presented results is that two different G·T(wWC)↔G·T*(WC)↔G*·T(WC) and G·T(rwWC)↔G*·T(rWC)↔G*·T(WC) routes guarantee almost the same probability of the acquisition by the wobble G·T(wWC) and reverse wobble G·T(rwWC) base pairs of the G*·T(WC) Watson–Crick-like configuration. Notably, that reverse wobble G·T(rwWC) and reverse Watson–Crick G·T*O2(rWC) base pairs tautomerise via the double proton transfer along the intermolecular H-bonds – G·T(rwWC)↔G*·T*(rwWC) and G·T*O2(rWC)↔G+·T−(rWC)↔G*·T(rWC), respectively. It was also considered conformational mobility of the G·T*(WC), G·T*O2(rWC), G·T(wWC), G·T(rwWC), G*·T*(rwWC) and G*·T(rWC) base pairs through the mutual rotation of the bases around the intermolecular H-bond. Methods of the structural bioinformatics have been used for indication of the G·T base pairs in real biological systems. Revealed conformationally-tautomeric transformations can explain transitions of the DNA molecule from parallel to anti-parallel conformations and vice versa.
https://www.tandfonline.com/eprint/5UZNR95UAUXNVGM3B2JM/full?target=10.1080/00268976.2022.2026510
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·CO2*(rWC), GN2*·C(rWC), G*′N2·C(rWC), GN7*·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.
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