Inferring 3D Residue Contacts of Protein Complexes From Evolutionary Sequence Variations

Abstract

Protein-protein interaction is critical for the biological functions of living organisms. Experimental screens and structural biology have provided detailed insight into the interactions of many protein complexes, but most interactions are still unknown. A rich source of information for protein interactions is the evolutionary sequence record. Analysis of correlated evolutionary sequence changes across proteins had identified residues in close spatial proximity of each other with sufficient accuracy to determine the three-dimensional (3D) structure of protein monomers. In this study, we applied coevolution analysis to predict 3D residue contacts between proteins within complexes of self-associating Escherichia coli CTP synthetase and Thermotoga maritima MreB. Coevolution analysis did not robustly predict inter-protein residue contacts for either protein complexes. From additional analyses, we believe that this low prediction yield was not due to lack of conservation of the protein-protein interaction interface. Thus, further study is required to improve the analysis for the robust prediction of protein-protein contacts.