Identifying Protein-Protein Interaction Sites on a Genome-Wide Scale

Abstract

Protein interactions typically arise from a physical interaction of one or more small sites on the surface of the two proteins. Identifying these sites is very important for drug and protein design. In this paper, we propose a computational method based on probabilistic relational model that at- tempts to address this task using high-throughput protein interaction data and a set of short sequence motifs. We learn the model using the EM algorithm, with a branch-and-bound algorithm as an approximate infer- ence for the E-step. Our method searches for motifs whose presence in a pair of interacting proteins can explain their observed interaction. It also tries to determine which motif pairs have high affinity, and can therefore lead to an interaction. We show that our method is more accurate than others at predicting new protein-protein interactions. More importantly, by examining solved structures of protein complexes, we find that 2/3 of the predicted active motifs correspond to actual interaction sites.