Computational identification of inhibitors of protein-protein interactions.

Zhong, Shijun; Macias, Alba T; MacKerell, Alexander D

The ability to control protein-protein interactions (PPIs) for therapeutic purposes is attractive since many processes in cells involve such interactions. Recent successes in the discovery of small molecules that target protein-protein interactions for drug development have shown that targeting these interactions is indeed feasible. In the present review the use of computer-aided drug design (CADD) via database screening or docking algorithms for identifying inhibitors of protein-protein interactions is introduced. The principles of database screening and a practical protocol for targeting PPIs are described. The recent applications of these approaches to different systems involving protein-protein interactions, including BCL-2, S100B, ERK and p56lck, are presented and provide valuable examples of inhibitor discovery and design.