InterPred: A pipeline to identify and model protein–protein interactions

Claudio Mirabello, Björn Wallner

Protein-protein interactions (PPI) are crucial for protein function. There exist many techniques to identify PPIs experimentally, but to determine the interactions in molecular detail is still difficult and very time-consuming. The fact that the number of PPIs is vastly larger than the number of individual proteins makes it practically impossible to characterize all interactions experimentally. Computational approaches that can bridge this gap and predict PPIs and model the interactions in molecular detail are greatly needed. Here we present InterPred, a fully automated pipeline that predicts and model PPIs from sequence using structural modelling combined with massive structural comparisons and molecular docking. A key component of the method is the use of a novel random forest classifier that integrate several structural features to distinguish correct from incorrect protein-protein interaction models. We show that InterPred represents a major improvement in protein-protein interaction detection with a performance comparable or better than experimental high-throughput techniques. We also show that our full-atom protein-protein complex modelling pipeline performs better than state of the art protein docking methods on a standard benchmark set. In addition, InterPred was also one of the top predictors in the latest CAPRI37 experiment. This article is protected by copyright. All rights reserved.