Abstract
In this study it was theoretically shown that discovered by us recently (Brovarets’ et al., Frontiers in Chemistry, 2018, 6:8; doi: 10.3389/fchem.2018.00008) high-energetical, significantly non-planar (symmetry C1), short-lived wobbled conformers of the classical Watson-Crick А·Т(WC), reverse Watson-Crick А·Т(rWC), Hoogsteen А·Т(Н) and reverse Hoogsteen А·Т(rН) DNA base pairs are the intermediates of their pairwise А∙Т(WC)/А∙Т(rWC) ↔ А∙Т(H)/А∙Т(rH) conformational transformations. These transitions do not require for their realization the energy-consumable anisotropic rotation of the amino group of A around the exocyclic C6-N6 bond. They are controlled by the non-planar transition states with quasi-orthogonal geometry (symmetry C1) joined by the single intermolecular (Т)N3H···N6(А) H-bond (~4 kcal∙mol−1). The Gibbs free energies of activation for these non-dissociative, dipole-active conformational transitions consist 7.33 and 7.81 kcal∙mol−1, accordingly. Quantum-mechanical (QM) calculations in combination with Bader’s quantum theory of “Atoms in Molecules” (QTAIM) have been performed at the MP2/aug-cc-pVDZ//B3LYP/6-311++G(d,p) level of QM theory in the continuum with ε = 4 under normal conditions.
Highlights
(symmetry C1), short-lived wobbled conformers of the classical Watson-Crick А·Т(WC), reverse WatsonCrick А·Т(rWC), Hoogsteen А·Т(Н) and reverse Hoogsteen А·Т(rН) DNA base pairs are the intermediates of their pairwise А∙Т(WC)/А∙Т(rWC) ↔ А∙Т(H)/А∙Т(rH) conformational transformations
We have calculated geometries of the basic and high-energetic conformers and transition states (TSs) of their mutual conformational transformations together with their harmonic vibrational frequencies at the B3LYP/6– 311++G(d,p) level of theory[36,37,38,39,40], using Gaussian’[09] package[41], in the continuum with ε = 4, which is typical for the processes in real biological complexes and taking into account the structural and functional characteristics of the bases in the duplex DNA and at the same time satisfactorily reflecting the environment in the essentially hydrophobic base-pair recognition pocket of the high-fidelity DNA-polymerase[42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66]
We considered the presence of the (3, −1) bond critical point (BCP), a bond path between the donor and acceptor of the intermolecular contact and positive value of the Laplacian at this BCP (Δρ > 0) as criteria for the existence of the H-bond or attractive van der Waals contact formation[73,74,75,76,77,78,79,80,81,82,83,84]
Summary
(symmetry C1), short-lived wobbled conformers of the classical Watson-Crick А·Т(WC), reverse WatsonCrick А·Т(rWC), Hoogsteen А·Т(Н) and reverse Hoogsteen А·Т(rН) DNA base pairs are the intermediates of their pairwise А∙Т(WC)/А∙Т(rWC) ↔ А∙Т(H)/А∙Т(rH) conformational transformations. These transitions do not require for their realization the energy-consumable anisotropic rotation of the amino group of A around the exocyclic C6-N6 bond. Thorough calculations by the method of molecular dynamics indicate that А·Т(WC) ↔ А·Т(Н) transitions of bps and anti ↔ syn transitions of the A around the glycosidic bond are closely correlated processes, for which Gibbs free energy of activation is 10–11 kcal∙mol−1 under normal conditions[8]. These specific intermolecular contacts involve pyramidalized A amino group, acting simultaneously as an acceptor and a donor of the H-bonding
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