Progress and challenges in predicting protein interfaces

*These authors contributed equally to this work. The majority of biological processes are mediated via protein–protein interactions. Determination of residues participating in such interactions improves our understanding of molecular mechanisms and facilitates the development of therapeutics. Experimental approaches to identifying interacting residues, such as mutagenesis, are costly and time-consuming and thus, computational methods for this purpose could streamline conventional pipelines. Here we review the field of computational protein interface prediction. We make a distinction between methods which address proteins in general and those targeted at antibodies, owing to the radically different binding mechanism of antibodies. We organize the multitude of currently available methods hierarchically based on required input and prediction principles to provide an overview of the field. Key words: protein–protein interaction; protein interface prediction; antibody antigen interaction Protein interfaces Proteins interact with other proteins, DNA, RNA and small mol-ecules to perform their cellular tasks. Knowledge of protein interfaces and the residues involved is vital to fully understand molecular mechanisms and to identify potential drug target