WATER MEDIATED PROTEIN-DNA INTERACTIONS - THE RELATIONSHIP OF THERMODYNAMICS TO STRUCTURAL DETAIL

The elucidation of a relationship between the thermodynamic parameters and the structural changes accompanying biomolecular interactions cou ld lead to predictive algorithms. For example, based on some knowledge of the structure of a target molecule the affinities of ligands could be determined with obvious implications for the pharmaceutical indust ry. In attempting to relate the thermodynamic and structural changes o n formation of a protein-DNA complex, the correlation between change i n heat capacity and burial of surface area has proved successful. Howe ver, this correlation appears to break down when water molecules are i ncluded in the binding interface. Here we present data that support th e hypothesis that bound water molecules have to be considered as contr ibuting to the change in heat capacity and could, thus, be used in lig and design.