2P2Idb is a hand-curated structural database dedicated to the modulation of protein-protein interactions (PPIs). It includes all interactions for which both the protein-protein and protein-modulator complexes have been structurally characterized by X-ray or NMR (1,2). The 2P2I database currently contains 14 protein-protein complexes, 16 free proteins, 56 protein-ligand complexes and 53 small molecule inhibitors. Only inhibitors found at the interface (orthosteric modulators) have been considered in this version of the database. The web server provides links to related sites of interest, binding affinity data, pre-calculated structural information about protein-protein interfaces and 3D interactive views through java applets.
An original tool (2P2Iinspector) has been developed to calculate, from a 3D structure, a series of parameters that characterize proteinâ€“protein interfaces. A large range of biophysical and geometrical descriptors are computed including, buried accessible surface area, gap volume, non-bonded contacts, hydrogen-bonds, atom and residue composition, number of segments and secondary structure contribution.
A qualitative scoring function is proposed to assess the druggability of PPIs. Users can compare parameters from their own protein-protein interface to a distribution of parameters from the 2P2Idb dataset. A qualitative score is given for each parameter and a color coded table provides the deviation of each parameter compared to the mean of the same parameter in the equivalent 2P2I cluster.
1. Basse, M.J., Betzi, S., Bourgeas, R., Bouzidi, S., Chetrit, B., Hamon, V., Morelli, X. and Roche, P. 2P2Idb: A Structural Database Dedicated to Orthosteric Modulation of Protein-Protein Interactions. Nucleic Acid Research, 41, in press.
2. Bourgeas, R., Basse, M.-J., Morelli, X. and Roche, P. (2010) Atomic Analysis of Protein-Protein Interfaces with Known Inhibitors: The 2P2I Database. PLoS ONE, 5, e9598.