AN ANALYSIS OF THE RELATIONSHIP BETWEEN HYDRATION AND PROTEIN-DNA INTERACTIONS

Eleven protein-DNA crystal structures were analyzed to test the hypoth esis that hydration sites predicted in the first hydration shell of DN A mark the positions where protein residues hydrogen-bond to DNA. For nine of those structures, protein atoms, which form hydrogen bonds to DNA bases, were found within 1.5 Angstrom of the predicted hydration p ositions in 86% of the interactions. The correspondence of the predict ed hydration sites with the hydrogen-bonded protein side chains was si gnificantly higher for bases inside the conserved DNA recognition sequ ences than outside those regions. In two CAP-DNA complexes, predicted base hydration sites correctly marked 71% (within 1.5 Angstrom) of pro tein atoms, which form hydrogen bonds to DNA bases. Phosphate hydratio n was compared to actual protein binding sites in one CAP-DNA complex with 78% marked contacts within 2.0 Angstrom. These data suggest that hydration sites mark the binding sites at protein-DNA interfaces.