Effect of a water molecule on the sugar puckering of uridine, 2'-deoxyuridine, and 2'-O-methyl uridine inserted in duplexes.

We used high-level quantum mechanical calculations to determine the pucker (north type or south type) of various compounds: uridine, 2'-deoxyuridine, and 2'-O-methyl uridine. Although the dihedrals of the backbone are set close to their experimental values in double-stranded nucleic acids, calculations using density functional theory show that, in vacuo or in a continuum mimicking the dielectric properties of water, the south puckering conformations of uridine is favored. This contrasts with experimental data: most ribonucleosides inserted into a duplex have the north puckering. We show here that the north puckering is favored when an explicit water molecule is introduced into the calculation. The orientations of the 2' group and of the water molecule have implications for the prevalence of the north puckering. We studied several orientations of the water molecule binding uracil O2 and the 2' group and estimated the energy barriers in the path between the north-to-south conformations. The north puckering is more favored in 2'-OH than in 2'-OCH3 compounds in the presence of the explicit water molecule.