Most proteins interact with small-molecule ligands such as metabolites or drug compounds. Over the past several decades, many of these interactions have been captured in high-resolution atomic structures. From a geometric point of view, most interaction sites for grasping these small-molecule ligands, as revealed in these structures, form concave shapes, or pockets, on the proteins surface. An efficient method for comparing these pockets could greatly assist the classification of ligand-binding sites, prediction of protein molecular function and design of novel drug compounds.