Base pair compositional variability influences DNA structural stability and tunes hydration thermodynamics and dynamics.

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DNA deformability and differential hydration are crucial determinants of biological processes ranging from genetic material packaging to gene expression; their associative details, however, remain inadequately understood. Herein, we report investigations of the dynamic and thermodynamic responses of the local hydration of a variety of base pair sequences. Leveraging in silico sampling and our in-house analyses, we first report the local conformational propensity of sequences that are either predisposed toward the canonical A- or B-conformations or are restrained to potential transitory pathways. It is observed that the transition from the unrestrained A-form to the B-form leads to lengthwise structural deformation. The insertion of intermittent -(CG)- base pairs in otherwise homogeneous -(AT)- sequences bears dynamical consequences for the vicinal hydration layer. Calculation of the excess (pair) entropy suggests substantially higher values of hydration water surrounding A conformations over the B- conformations. Applying the Rosenfeld approximation, we project that the diffusivity of water molecules proximal to canonical B conformation is least for the minor groove of the canonical B-conformation. We determine that structure, composition, and conformation specific groove dimension together influence the local hydration characteristics and, therefore, are expected to be important determinants of biological processes.