for collection of various chemical compounds binding to related binding pockets. Such comprehensive information of protein–ligand interactions is expected to be useful for drug design. To demonstrate the ability of our database to predict the type of bound ligand for unbound protein structures, an application of SearchP is presented below. First, we selected an unbound protein structure (PDB ID: 3K0B), as obtained from a structural genomics project, as a query for use in this demonstration. We then explored similar known ligand-binding sites for the query using SearchP, and retrieved 46 hits with aligned length of more than 10 residues. Of those, the top 38 hits were binding sites of S-adenosylmethionine (SAM) or S-adenosyl-L-homo- cysteine (SAH). The most similar hits were a SAH- binding site of 2ORE: 24 residues were aligned with RMSD 1.81 A˚ , as shown in Figure 5B. Furthermore, the 38 hits were from 21 different proteins whose EC numbers are limited to ‘2.1.1.72’ and ‘2.1.1.-’. These results strongly indicate that the query protein structure can be bound with a S-adenosyl-(L)-methionine or its product S-adenosyl-(L)-homocysteine, and can be involved in methyltransferases (EC: 2.1.1.-), or more speciﬁcally, site-speciﬁc DNA-methyltransferase (EC: 2.1.1.72). This example demonstrates the utility of SearchP for predicting the type of binding ligand and function for structures whose function is unclear. SUMMARY AND FUTURE WORK We presented a database PoSSuM for ﬁnding similar protein–ligand binding sites. We believe that our database is a powerful tool for the annotation of protein functions and for structure-based drug design. PoSSuM will be updated as new protein structures are accumulated in the PDB. As of August 2011, PoSSuM includes over 14 million similar pairs of both known and putative-binding sites of non-polymer small molecules. We plan to include all PDB entries of proteins into our database for SearchP in the next update. Searching known ligand-binding sites similar to potential ones of a structure of the users’ own is expected to be useful. We are developing our server so that users can upload their protein structures and analyze their potential binding sites. In addition to or instead of Ghecom, applying other method(s) to detect potential ligand-binding sites is expected to be beneﬁcial. For example, using PocketFinder (11), unlike Ghecom, which ﬁnds potential ligand-binding envelopes rather than binding pockets on protein surface, can engender enhanced discovery of novel or hidden ligand-binding sites. We intend to improve our database in this direction. In the near future, we plan to extend our data set to binding interfaces of proteins to proteins and to nucleic acids. 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