Molecular Origin of Distinct Hydration Dynamics in Double Helical DNA and RNA Sequences

Water molecules are essential to determine the structure of nucleic acids and mediate their interactions with other biomolecules. Here, we characterize the hydration dynamics of analogous DNA and RNA double helices with unprecedented resolution and elucidate the molecular origin of their differences: first, the localization of the slowest hydration water molecules─in the minor groove in DNA, next to phosphates in RNA─and second, the markedly distinct hydration dynamics of the two phosphate oxygen atoms O and O in RNA. Using our Extended Jump Model for water reorientation, we assess the relative importance of previously proposed factors, including the local topography, water bridges, and the presence of ions. We show that the slow hydration dynamics at RNA O sites is not due to bridging water molecules but is caused by both the larger excluded volume and the stronger initial H-bond next to O, due to the different phosphate orientations in A-form double helical RNA.