A Computational Model for Predicting Protein Interactions Based on Multidomain Collaboration

Recently, several domain-based computational models for predicting protein-protein interactions (PPIs) have been proposed. The conventional methods usually infer domain or domain combination (DC) interactions from already known interacting sets of proteins, and then predict PPIs using the information. However, the majority of these models often have limitations in providing detailed information on which domain pair (single domain interaction) or DC pair (multidomain interaction) will actually interact for the predicted protein interaction. Therefore, a more comprehensive and concrete computational model for the prediction of PPIs is needed. We developed a computational model to predict PPIs using the information of intraprotein domain cohesion and interprotein DC coupling interaction. A method of identifying the primary interacting DC pair was also incorporated into the model in order to infer actual participants in a predicted interaction. Our method made an apparent improvement in the PPI prediction accuracy, and the primary interacting DC pair identification was valid specifically in predicting multidomain protein interactions. In this paper, we demonstrate that 1) the intraprotein domain cohesion is meaningful in improving the accuracy of domain-based PPI prediction, 2) a prediction model incorporating the intradomain cohesion enables us to identify the primary interacting DC pair, and 3) a hybrid approach using the intra/interdomain interaction information can lead to a more accurate prediction.