Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.13.295196v1?rss=1 Authors: Yan, Y., Huang, S.-Y. Abstract: Protein-protein interactions play a fundamental role in all cellular processes. Therefore, determining the structure of protein-protein complexes is crucial to understand their molecular mechanisms and develop drugs targeting the protein-protein interactions. Recently, deep learning has led to a breakthrough in intraprotein contact prediction, achieving an unusual high accuracy in recent CASP structure prediction challenges. However, due to the limited number of known homologous protein-protein interactions and the challenge to generate joint multiple sequence alignments (MSA) of two interacting proteins, the advances in inter-protein contact prediction remain limited. Here, we have proposed a deep learning model to predict inter-protein residue-residue contacts across homo-oligomeric protein interfaces, named as DeepHomo, by integrating evolutionary coupling, sequence conservation, distance map, docking pattern, and physic-chemical information of monomers. DeepHomo was extensively tested on both experimentally determined structures and realistic CASP-CAPRI targets. It was shown that DeepHomo achieved a high accuracy of >60% for the top predicted contact and outperformed state-of-the-art direct-coupling analysis (DCA) and machine learning (ML)-based approaches. Integrating predicted contacts into protein docking with blindly predicted monomer structures also significantly improved the docking accuracy. The present study demonstrated the success of DeepHomo in inter-protein contact prediction. It is anticipated that DeepHomo will have a far-reaching implication in the inter-protein contact and structure prediction for protein-protein interactions. Copy rights belong to original authors. Visit the link for more info