Characterizing hydration sites in protein-ligand complexes towards the design of novel ligands

Water is an essential part of protein binding sites and mediates interactions to ligands. Its displacement by ligand parts affects the free binding energy of resulting protein-ligand complexes. Therefore the characterization of solvation properties is important for design. Of particular interest is the propensity of localized water to be favorably displaced by a ligand. This review discusses two popular computational approaches addressing these questions, namely WaterMap based on statistical mechanics analysis of MD simulations and 3D RISM based on integral equation theory of liquids. The theoretical background and recent applications in structure-based design will be presented.