Stacking of the mutagenic base analogue 5-bromouracil: energy landscapes of pyrimidine dimers in gas phase and water

Abstract

The potential energy surfaces of stacked base pairs consisting of cytosine (C), thymine (T), uracil (U) and the mutagenic thymine analogue 5-bromouracil (BrU) have been searched to obtain all possible minima. Minima and transition states were optimised at the counterpoise-corrected M06-2X/6-31+G(d) level, both in the gas phase and in water, modelled by the polarizable continuum model. The stacked dimers studied are BrU/BrU, C/BrU, C/C, C/T, C/U, T/BrU and T/U. Both face-to-back and face-to-face structures were considered. Free energies were calculated at 298.15 K. Together with U/U, T/T and BrU/U results from previous work, these results complete the family consisting of every stacked dimer combination consisting of C, T, U and BrU. The results were used to assess the hypothesis suggested in the literature that BrU stacks stronger than T, which could stabilise the mispair formed by BrU and guanine. In the gas phase, structures of C/BrU, T/BrU and U/BrU with greater zero-point-corrected binding energies than C/T, T/T and U/T, respectively, were found, with differences in favour of BrU of 3.1 kcal mol(-1), 1.7 kcal mol(-1) and 0.5 kcal mol(-1), respectively. However, the structure of these dimers differed considerably from anything encountered in DNA. When only the dimers with the most "DNA-like" twist (±36°) were considered, C/BrU and T/BrU were still more strongly bound than C/T and T/T, by 0.5 kcal mol(-1) and 1.7 kcal mol(-1), respectively. However, when enthalpic and/or solvent contributions were taken into account, the stacking advantage of BrU was reversed in the gas phase and mostly nullified in water. Enhanced stacking therefore does not seem a plausible mechanism for the considerably greater ability of BrU-G mispairs over T-G mispairs to escape enzymatic repair.

Atypical structures of GAA/TTC trinucleotide repeats underlying Friedreich’s ataxia: DNA triplexes and RNA/DNA hybrids

“…However, for the third strand in the triple helix this method may not work so well, as shown in the extreme example of Supplementary Figure S2.b , where all bases are perfectly stacked but not linked to the duplex. We notice that according to first principles calculations, the stacking of DNA bases is not the sandwich stacking presumed by the maximum overlap area, but a parallel-displaced stacking whose stacking interaction is influenced by relative shift and twist ( 82 , 83 ). Also, it is noted that there exists an inter-strand stacking interaction, which is as important as intra-strand although it needs no overlap area ( 84 ).…”

Clustering of Uracil Molecules on Ice Nanoparticles

“…Additional interactions between the two monomers can be as strong as 11 kcal/mol, in particular in the hydrogen-bonded structures. Although the interaction energies calculated for the gas phase stacked BrU dimer accounts for about 10 kcal/mol, in our optimization procedure performed on the ice surface the two BrU monomers tend to adopt slightly displaced structures. The calculations provide similar picture as for uracil, in particular, variety of binding motives to the ice cluster resulting in a large range of binding energies.…”

Relative Populations of Some Tautomeric Forms of 2′-Deoxyguanosine-5-Fluorouridine Mismatch

“…This statement is based on some facts that other factors have small effects on the HB structures. For example, it is stated that the base stacking effect as another factor in double helix formation is ignorable because its effect is negligible in comparison to the HB geometry and conformational variety. , Thus, data on these nucleoside pairs, modified by the sugar residue, can be transferred to a transcription result.…”