Statistical mechanical treatment of the structural hydration of biological macromolecules: Results forB-DNA

We constructed an efficient and accurate computational tool based on the potentials-of-mean-force approach for computing the detailed hydrophilic hydration of complex molecular structures in aqueous environments. Using the pair and triplet correlation functions database previously obtained from computer simulations of the simple point charge model of water, we computed the detailed structural organization of water around two B-DNA molecules with sequences d (AATT) ₃ (AATT) ₃ and d (CCGG) ₃ (CCGG) ₃, and canonical structure. A, T, C, and G denote adenine, thymine, cytosine, and guanine, respectively, and d (. . . ) denotes the deoxyribose in the sugar-phosphate backbone. The results obtained are in agreement with the experimental observations. A base-pair stretches are found to support the marked minor-groove ``spines of hydration'' observed in x-ray crystal structures. The hydrophilic hydration of the minor groove of the molecule d (CCGG) ₃ (CCGG) ₃ exhibits a double ribbon of high water density, which is also in agreement with x-ray crystallography observations of C base-pair regions. The major grooves, on the other hand, do not show a comparably strong localization of water molecules. The quantitative results are compared with a computer simulation study of Forester et al. Mol. Phys. 72, 643 (1991). We find good agreement for the hydration of the -NH₂ groups, the cylindrically averaged water density distributions, and the overall hydration number. The agreement is less satisfactory for the phosphate groups. However, by refining the treatment of the anionic oxygens on the phosphate groups, almost full quantitative agreement is achieved.