Progress and challenges in predicting protein interfaces

Abstract

Themajority of biological processes aremediated via protein-protein interactions. Determination of residues participating in such interactions improves our understanding ofmolecularmechanisms and facilitates the development of therapeutics. Experimental approaches to identifying interacting residues, such asmutagenesis, are costly and time-consuming and thus, computationalmethods for this purpose could streamline conventional pipelines. Here we review the field of computational protein interface prediction.Wemake a distinction betweenmethods which address proteins in general and those targeted at antibodies, owing to the radically different bindingmechanismof antibodies.We organize themultitude of currently available methods hierarchically based on required input and prediction principles to provide an overview of the field.