| Abstract
| - UV irradiation at 254 nm of 2‘-O,5-dimethyluridylyl(3‘-5‘)-2‘-O,5-dimethyluridine (1a) and of naturalthymidylyl(3‘-5‘)thymidine (1b) generates the same photoproducts (CPD and (6−4)PP; responsible for celldeath and skin cancer). The ratios of quantum yields of photoproducts obtained from 1a (determined herein)to that from 1b are in a proportion close to the approximately threefold increase of stacked dinucleotides for1a compared with those of 1b (from previous circular dichroism results). 1a and 1b however are endowedwith different predominant sugar conformations, C3‘-endo (1a) and C2‘-endo (1b). The present investigationof the stacked conformation of these molecules, by unrestrained state-of-the-art molecular simulation in explicitsolvent and salt, resolves this apparent paradox and suggests the following main conclusions. Stackeddinucleotides 1a and 1b adopt the main characteristic features of a single-stranded A and B form, respectively,where the relative positions of the backbone and the bases are very different. Unexpectedly, the geometry ofthe stacking of two thymine bases, within each dinucleotide, is very similar and is in excellent agreementwith photochemical and circular dichroism results. Analyses of molecular dynamics trajectories withconformational adiabatic mapping show that 1a and 1b explore two different regions of conformational spaceand possess very different flexibilities. Therefore, even though their base stacking is very similar, thesemolecules possess different geometrical, mechanical, and dynamical properties that may account for thediscrepancy observed between increased stacking and increased photoproduct formations. The computed averagestacked conformations of 1a and 1b are well-defined and could serve as starting models to investigatephotochemical reactions with quantum dynamics simulations.
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