Physical interactions between proteins are important for many cellular functions. Since protein-protein interactions are mediated via their interaction sites, identifying these interaction sites can therefore help to discover genome-scale protein interaction map, thereby leading to a better understanding of the organization of living cell. To date, the experimentally solved protein interaction sites constitute only a tiny proportion among the whole population due to the high cost and low-throughput of currently available techniques. Computational methods, including many biological data mining methods, are considered as the major approaches in discovering protein interaction sites in practical applications. This chapter reviews both traditional and recent computational methods such as protein-protein docking and motif discovery, as well as new methods on machine learning approaches, for example, interaction classification, domain-domain interactions, and binding motif pair discovery.
