Molecular design opportunities presented by solvent‐exposed regions of target proteins

Abstract Solvent‐exposed regions, or solvent‐filled pockets, within or adjacent to the ligand‐binding sites of drug‐target proteins provide opportunities for substantial modifications of existing small‐molecular drug molecules without serious loss of activity. In this review, we present recent selected examples of exploitation of solvent‐exposed regions of proteins in drug design and development from the recent medicinal‐chemistry literature.