Solvation Methods for Protein–Ligand Docking

Abstract

Hydration has a significant impact on ligand binding within protein active sites. Specific water molecules and their placement within protein active sites have been shown to make specific contributions to the energetics of protein-ligand binding and need consideration in the design of efficient binding ligands. These specific nonbulk water molecules and their interactions are different and have more significant impact in ligand design than the generalized bulk solvation of ligand-protein systems. Proper theoretical description of the solvation effects of water within a ligand-binding pocket is a significant computational challenge. Recently, new computational methods have been developed which can more accurately describe the contribution of waters within a protein ligand site and lead to improved and enhanced ligand design and ranking in computational docking and to greater enrichment.