atomic analysis of protein-protein interfaces with known inhibitors the 2p2i database原子的分析蛋白质与已知的抑制剂2 p2i数据库接口.pdf

Atomic Analysis of Protein-Protein Interfaces with Known Inhibitors: The 2P2I Database ¨ . . Raphael Bourgeas, Marie-Jeanne Basse, Xavier Morelli* , Philippe Roche* ´ ´ Laboratoire Interactions et Modulateurs de Reponses (UPR3243), Centre National de la Recherche Scientifique (CNRS) Aix-Marseille Universites, Institut de Microbiologie ´ ´ de la Mediterranee (IMM), Marseille, France Abstract Background: In the last decade, the inhibition of protein-protein interactions (PPIs) has emerged from both academic and private research as a new way to modulate the activity of proteins. Inhibitors of these original interactions are certainly the next generation of highly innovative drugs that will reach the market in the next decade. However, in silico design of such compounds still remains challenging. Methodology/Principal Findings: Here we describe this particular PPI chemical space through the presentation of 2P2IDB, a hand-curated database dedicated to the structure of PPIs with known inhibitors. We have analyzed protein/protein and protein/inhibitor interfaces in terms of geometrical parameters, atom and residue properties, buried accessible surface area and other biophysical parameters. The interfaces found in 2P2IDB were then compared to those of representative datasets of heterodimeric complexes. We propose a new classification of PPIs with known inhibitors into two classes depending on the number of segments present at the interface and corresponding to either a single secondary structure element or to a more globular interacting domai