The A·T(rWC)/A·T(H)/A·T(rH) ↔ A·T*(rw_WC)/A·T*(w_H)/A·T*(rw_H) mutagenic tautomerizationviasequential proton transfer: a QM/QTAIM study

Abstract

We discovered tautomeric wobbling of the classical A·T DNA base pairs. This data evidence, that only a base pair with Watson–Crick architecture can be a building block of the DNA macromolecule as a genetic material, which is able for the evolutionary self-development.

Novel Tautomerisation Mechanisms of the Biologically Important Conformers of the Reverse Löwdin, Hoogsteen, and Reverse Hoogsteen G*·C* DNA Base Pairs via Proton Transfer: A Quantum-Mechanical Survey

“…Thus, in particular, in previous works (Hoogsteen, 1963; Pous et al, 2008; Brovarets' and Hovorun, 2010, 2014b, 2015f; Brovarets', 2013a,b; Alvey et al, 2014; Nikolova et al, 2014; Acosta-Reyes et al, 2015; Poltev et al, 2016; Zhou, 2016; Szabat and Kierzek, 2017; Ye et al, 2017; Brovarets' et al, 2018a,b,c,d,e,f; Brovarets' and Tsiupa, 2019) by the methods of quantum chemistry we have investigated in details the potential (electronic) energy surface of each of the four biologically important A·T DNA base pairs—Watson-Crick A·T(WC), reverse Watson-Crick A·T(rWC), Hoogsteen A·T(H) and reverse Hoogsteen A·T(rH), leading to the novel conformational or tautomeric states of these base pairs. It was theoretically demonstrated that these A·T(WC/rWC/H/rH) base pairs possess unique ability to perform conformationally-tautomeric transition into the planar wobble A * ·T(w), A·TO2*(w), and A·T * (w) base mispairs, non-planar wobble A·T(w WC ), A·T(w rWC ), A·T(w H ), and A·T(w rH ) base mispairs and incorrect A·T * (wWC⊥), A·TO2*(wrWC⊥), A·T * (wH⊥), and A·TO2*(wrH⊥) base mispairs containing mutagenic tautomers of the DNA bases, and also their interconversions between each other through the non-planar transition states via the structural or conformational rearrangements and intramolecular proton transfer along the intermolecular H-bonds.…”

“…At this, the so-called Löwdin G * ·C * (WC) base pair with geometry close to Watson-Crick, which is created in such a way, involving mutagenic tautomers of the DNA bases, can acquire similarly to the A·T(WC) base pair different conformations (Brovarets' and Hovorun, 2010, 2015f; Brovarets', 2013a,b; Brovarets' et al, 2018a,b,c,d,e,f; Brovarets' and Tsiupa, 2019)—reverse Löwdin G * ·C * (rWC), Hoogsteen G * ′·C * (H) and reverse Hoogsteen G * ′·C * (rH) (Brovarets', 2013b) (here and below the superscript “ * ” denotes the rare tautomeric form of the DNA base (Glushenkov and Hovorun, 2016) and “′”— trans -orientation of the OH group). This demonstrates quite unexpected role of the Löwdin's tautomerisation for the conformational variety.…”

“…In this study, we aim to reapply the approach, which we launched in our previous works (Brovarets' et al, 2018a,b,c,d,e,f; Brovarets' and Tsiupa, 2019) in order to investigate in details the tautomerisation of the reverse Löwdin G * ·C * (rWC), Hoogsteen G * ′·C * (H), and reverse Hoogsteen G * ′·C * (rH) base pairs via PT along the neighboring intermolecular H-bonds.…”

The Role of Proton Transfer on Mutations

“…Results indicated that the non-dissociative transitions occurred via specific intermolecular interaction along the intrinsic reaction coordinate (IRC) (Brovarets' and Pérez-Sánchez, 2017). It showed that the tautomeric transitions for A·T DNA base pairs are non-planar and high-energetic intrapair bases (Brovarets' and Hovorun, 2014a, 2015b,d; Brovarets' et al, 2015, 2018a,b,c,d).…”

Novel pathway for mutagenic tautomerization of classical А∙Т DNA base pairs via sequential proton transfer through quasi-orthogonal transition states: A QM/QTAIM investigation

“…The tautomerization products—the A*∙Т(rw WC ), A* N7 ∙Т(rw H ) and A* N7 ∙Т(w H ) pairs—further transform via concerted asynchronous double proton transfer into the energetically favorable wobble A∙T*(rw WC ), A∙T*(rw H ) and A∙T* O2 (w H ) mispairs (symmetry C s ), respectively. Moreover, it was established in our recent papers, that wobble A*∙T(rw WC ) base mispair can also be formed from the reverse A∙T(rWC) base pair [ 20 ], A*·T(wWC) base mispair—from the canonical A∙T(rWC) base pair [ 19 ] and A* N7 ·Т(w H ) base mispair—from the Hoogsteen A∙T(H) base pair [ 20 ].…”