Proton-transfer in hydrogenated guanine–cytosine trimer neutral species, cations, and anions embedded in B-form DNA

Abstract

The neutral DNA trimers with the hydrogen atom added to the C8 site of the middle guanine-cytosine (GC) base pair, the DNA trimers protonated at the N7 site of the middle GC base pair, and the anionic species resulting from hydride addition to the C6 site of the middle GC base pair are investigated using theoretical methods. The canonical Watson-Crick structures (WC), transition state structures (TS) and proton-transferred structures (PT) of each relevant system are optimized in the gas phase and in aqueous solution, in order to understand the processes of proton transfer. The proton transfer reactions of the DNA trimers are compared with the corresponding isolated hydrogenated GC base pairs to explore the influence of the surrounding molecules and the base sequence. The proton transfer reactions of the neutral species, cations, and anions are compared, aiming to clarify the effects of the system's total charge. The results reveal that the surrounding molecules decrease the reaction energies of proton-transfer in aqueous solution. The structures with the dATGCAT and dGCGCGC sequences facilitate proton H4a transfer, but hinder proton H1 transfer. The structures with the dCGGCCG and dTAGCTA sequences facilitate proton H1 transfer. The net charge on the system plays an important role in determining the single and double proton-transfer patterns. Anions are more likely to experience proton-transfer reactions than neutral species and cations, and all the proton-transfer reactions of the anions are exothermic.

A novel conception for spontaneous transversions caused by homo-pyrimidine DNA mismatches: a QM/QTAIM highlight

“…An intriguing theme of the origin of the spontaneous point mutations has excited researches' mind during several decades suggesting DNA mispairs as their source [1][2][3][4][5][6]. Characterizing current state of this biologically important area of knowledge, it can be certainty stated that one of the stumbling stones in the theory of spontaneous point mutagenesis, which slowly gets on its feet, is understanding of the nature of the spontaneous transversions [7][8][9][10] caused by the homo-pyrimidine DNA base mispairs.…”

DNA spontaneous mutation and its role in the evolution of GC-content: assessing the impact of the genetic sequence

“…As any model, these chemical systems are simplified representations of the reality, but they allow to accurately predict the frequency at which rare tautomers appear during cell replication if a quantum mechanical treatment is applied. 26 All d(5 0 -XGX-3 0 ) sequences were generated with the X3DNA software package. 36 More specifically, we use X3DNA to built up the double-stranded B-form DNA trimers applying the default parameters (twist = 361; rise = 3.375 Å).…”

“…In order to maintain a reasonable computational cost, we decided to use a hybrid QM:QM 0 approach in which the geometry of the central GC base pair is optimized at the M06-2X/6-31G(d) level, 37 successfully used for modelling DNAtrimers 26 and that correctly reproduce p-stacking effects, 38 while the rest of the system was frozen in space and described at the same level of theory (border basis pairs) or with PM6 39 (sugar-phosphate backbone). Such a computational strategy correctly mimics the characteristic double helix form and simultaneously allows one to relax the central base during the mutagenic process.…”

“…In a recent work, Wang, Schaefer-III and co-workers have shown that the genetic sequence affects the PT in damaged DNA by adding H , H + and H À entities at several positions in the GC base pairs. 26 These authors built up a series of hydrogenated-GC to subsequently explore the induced tautomeric equilibria. Their simulations revealed that the PT mechanisms depend on the sequence in these hydrogenated-DNA structures.…”

“…Their simulations revealed that the PT mechanisms depend on the sequence in these hydrogenated-DNA structures. 26 There is however an important unanswered question: does the genetic sequence impact on the stability of the spontaneous mutation? In other words, is there a relationship between the sequence and the GC -G*C* conversion rate in undamaged-DNA?…”