2P2Idb is a hand-curated structural database dedicated to protein–protein interactionswith known small molecule orthosteric modulators. It compiles the structural informationrelated to orthosteric inhibitors and their target [i.e. related 3D structures available in theRCSB Protein Data Bank (PDB)] and provides links to other useful databases. 2P2Idb includesall interactions for which both the protein–protein and protein–inhibitor complexeshave been structurally characterized. Since its first release in 2010, the databasehas grown constantly and the current version contains 27 protein–protein complexesand 274 protein–inhibitor complexes corresponding to 242 unique small molecule inhibitorswhich represent almost a 5-fold increase compared to the previous version. A numberof new data have been added, including new protein–protein complexes, bindingaffinities, molecular descriptors, precalculated interface parameters and links to otherwebservers. A new query tool has been implemented to search for inhibitors within thedatabase using standard molecular descriptors. A novel version of the 2P2I-inspectortool has been implemented to calculate a series of physical and chemical parameters ofthe protein interfaces. Several geometrical parameters including planarity, eccentricityand circularity have been added as well as customizable distance cutoffs. This tool hasalso been extended to protein–ligand interfaces. The 2P2I database thus represents awealth of structural source of information for scientists interested in the properties ofprotein–protein interactions and the design of protein–protein interaction modulators.Database URL: http://2p2idb.cnrs-mrs.fr