Novel physico-chemical mechanism of the mutagenic tautomerisation of the Watson–Crick-like A·G and C·T DNA base mispairs: a quantum-chemical picture

Abstract

The newly discovered physico-chemical mechanism of the mutagenic tautomerisation of the long A$G and short C$T Watson-Crick DNA base mispairs was revealed for the first time. The tautomerisation of each mismatch occurs via four topologically and energetically different ways through highly stable transition states -H-bonded tight ion pairs containing protonated and deprotonated bases. These processes are accompanied by a significant rebuilding of the base mispairs with a Watson-Crick architecture into wobble mismatches, which are shifted towards both the minor and major DNA grooves and vice versa. Moreover, it was established that these tautomerisation reactions occur non-dissociatively and are accompanied by the consequent replacement of the unique patterns of the specific intermolecular interactions along the IRC. Finally, we briefly discuss the possible biological significance of the obtained results for clarifying the microstructural foundations of the origin of the spontaneous point mutations within the framework of the classical Watson-Crick tautomeric hypothesis. † Electronic supplementary information (ESI) available: (i) Energetic characteristics of the investigated DNA mispairs; (ii) proles of the glycosidic parameters along the IRC of tautomerisation; (iii) energetic proles and parameters of the mismatch planarization. See

Can Cyanuric Acid and 2,4,6‐Triaminopyrimidine Containing Ribonucleosides be Components of Prebiotic RNA? Insights from QM Calculations and MD Simulations

“…Such prebiotic systems would have later evolved into extant self-replicating genome, which involves only canonical tautomers of nucleobases and their hydrogen-bonded pairs, and preferentially exclude unstable tautomeric forms. [63,64] Thus, our combined DFT and MD results reaffirm the candidature of CA and TAP as simpler, primitive genetic material that preceded RNA and support the prebiotic relevance of these heterocycles. Our analysis will hopefully inspire future studies on the synthesis, structural evaluation and prebiotic validation of model polymers consisting of these heterocycles .…”

“…Importantly, a narrower helix containing tightly‐packed prebiotic bases would shield the internal environment of such polymeric assemblies and aid their evolution into self‐replicating systems. Such prebiotic systems would have later evolved into extant self‐replicating genome, which involves only canonical tautomers of nucleobases and their hydrogen‐bonded pairs, and preferentially exclude unstable tautomeric forms …”

Unexpected A·T(WC)↔A·T(rWC)/A·T(rH) and A·T(H)↔A·T(rH)/A·T(rWC) conformational transitions between the classical A·T DNA base pairs: A QM/QTAIM comprehensive study

“…Interestingly, that among all without exception investigated in this work H‐bonded structures, total energy of the intermolecular H‐bonds consists only a part of the electron energy of the monomers interactions (see Figure ). This result agrees with the previously obtained data for the other H‐bonded pairs of nucleotide bases …”

Effect of the sulfur atom on S2 and S4 positions of the uracil ring in different DNA:RNA hybrid microhelixes with three nucleotide base pairs

“…In general, DFT methods appear as the most suitable today because they offer a compromise between the important demands put on computer power and time, and the desired chemical accuracy. Furthermore, these methods have been used satisfactorily in many spectroscopic studies, in nucleosides, DNA base pairs, water cluster of nucleobases, biological molecules, and in drug designing, in particular the M062X method selected here …”

“…Furthermore, these methods have been used satisfactorily in many spectroscopic studies, [36][37][38] in nucleosides, [39][40][41][42][43] DNA base pairs, [44,45] water cluster of nucleobases, [46] biological molecules, [47] and in drug designing, [48] in particular the M062X method selected here. [49][50][51] In the optimization process was used the Berny algorithm under the standard convergence criteria.…”