TY - JOUR T1 - Protein–Protein Interaction Hotspots Carved into Sequences A1 - Ofran, Yanay A1 - Rost, Burkhard Y1 - 2007/07/13 N2 -
Interactions between proteins underlie all biological processes. Hence, to fully understand or to control biological processes we need to unravel the principles of protein interactions. The quest for these principles has focused predominantly on the entire interfaces between two interacting proteins. However, it has been shown that only few of the interface residues are essential for the recognition and binding to other proteins. The identification of these residues, commonly referred to as binding “hotspots,” is a first step toward understanding the function of proteins and studying their interactions. Experimentally, hotspots could be identified by mutating single residues—an expensive and laborious procedure that is not applicable on a large scale. Here, we show that it is possible to identify protein interaction hotspots computationally on a large scale based on the amino acid sequence of a single protein, without requiring the knowledge of its interaction partner. Our results suggest that most protein complexes are stabilized by similar basic principles. The ability to accurately and efficiently identify hotspots from sequence enables the annotation and analysis of protein–protein interaction hotspots in an entire organism and thus may benefit function prediction and drug development.