dompep—a general method for predicting modular domain-mediated protein-protein interactions模块化domain-mediated dompep-a一般方法预测蛋白质相互作用.pdfVIP

DomPep—A General Method for Predicting Modular Domain-Mediated Protein-Protein Interactions 1 1 2 2 2 1 Lei Li , Bing Zhao , Jun Du , Kaizhong Zhang , Charles X. Ling , Shawn Shun-Cheng Li * 1 Department of Biochemistry, Siebens-Drake Medical Research Institute, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada, 2 Department of Computer Science, The University of Western Ontario, London, Ontario, Canada Abstract Protein-protein interactions (PPIs) are frequently mediated by the binding of a modular domain in one protein to a short, linear peptide motif in its partner. The advent of proteomic methods such as peptide and protein arrays has led to the accumulation of a wealth of interaction data for modular interaction domains. Although several computational programs have been developed to predict modular domain-mediated PPI events, they are often restricted to a given domain type. We describe DomPep, a method that can potentially be used to predict PPIs mediated by any modular domains. DomPep combines proteomic data with sequence information to achieve high accuracy and high coverage in PPI prediction. Proteomic binding data were employed to determine a simple yet novel parameter Ligand-Binding Similarity which, in turn, is used to calibrate Domain Sequence Identity and Position-Weighted-Matrix distance, two parameters that are used in constructing prediction models. Moreover, DomPep can be used to predict PPIs for both domains with experimental binding data and those without. Using the PDZ and SH2 domain families as test cases, we show that DomPep can predict PPIs with accuracies superior to existing methods. To evaluate DomPep as a