HYDRATION OF NUCLEIC-ACID FRAGMENTS - COMPARISON OF THEORY AND EXPERIMENT FOR HIGH-RESOLUTION CRYSTAL-STRUCTURES OF RNA, DNA, AND DNA-DRUG COMPLEXES

A computationally efficient method to describe the organization of wat er around solvated biomolecules is presented. It is based on a statist ical mechanical expression for the water-density distribution in terms of particle correlation functions. The method is applied to analyze t he hydration of small nucleic acid molecules in the crystal environmen t, for which high-resolution x-ray crystal structures have been report ed. Results for RNA [r(ApU) . r[ApU)] and DNA [d(CpG) . d(CpG) in Z fo rm and with parallel strand orientation] and for DNA-drug complexes [d (CpG) . d(CpG) with the drug proflavine intercalated] are described. A detailed comparison of theoretical and experimental data shows positi onal agreement for the experimentally observed water sites. The presen ted method can be used for refinement of the water structure in x-ray crystallography, hydration analysis of nuclear magnetic resonance stru ctures, and theoretical modeling of biological macromolecules such as molecular docking studies. The speed of the computations allows hydrat ion analyses of molecules of almost arbitrary size (tRNA, protein-nucl eic acid complexes, etc.) in the crystal environment and in aqueous so lution.