Pocket identification methods. a. POCKET, LIGSITE, and LIGSITEcscscan the grid for protein-solvent-protein and surface-solvent-surface events, respectively. POCKET uses 3, LIGSITE and LIGSITEcsc7 directions. POCKET and LIGSITE use atom coordinates while LIGSITEcscuses the Connolly surface. b. SURFNET places a sphere, which must not contain any atoms, between two atoms. The spheres with maximal volume define the largest pocket. c. CAST triangulates the surface atoms and clusters triangles by merging small triangles to neighbouring large triangles. d. PASS coats the protein with probe spheres, selects probes with many atom contacts, and then repeats coating until no new probes are kept. The pockets, or active site points, are the probes with large number of atom contacts.