Structural bioinformatics Prediction of protein–protein interactions by combining structure and sequence conservation in protein interfaces

Motivation: Elucidation of the full network of protein–protein interac-tions is crucial for understanding of the principles of biological systems and processes. Thus, there is a need for in silico methods for predicting interactions. We present a novel algorithm for automated predic-tion of protein–protein interactions that employs a unique bottom-up approach combining structure and sequence conservation in protein interfaces. Results: Running the algorithm on a template dataset of 67 interfaces and a sequentially non-redundant dataset of 6170 protein structures, 62 616 potential interactions are predicted. These interactions are compared with the ones in two publicly available interaction databases (Database of Interacting Proteins and Biomolecular Interaction Net-work Database) and also the Protein Data Bank. A significant number of predictions are verified in these databases. The unverified ones may correspond to (1) interactions that are not covered in these data-bases but known in literature, (2) unknown interactions that actually occur in nature and (3) interactions that do not occur naturally but may possibly be realized synthetically in laboratory conditions. Some unverified interactions, supported significantly with studies found in the literature, are discussed