a sequence and structure based method to predict putative substrates, functions and regulatory networks of endo proteases基于序列和结构的方法来预测假定的基质,endo蛋白酶的功能和监管网络.pdfVIP

A Sequence and Structure Based Method to Predict Putative Substrates, Functions and Regulatory Networks of Endo Proteases 1 1 2 1 1 Prasanna Venkatraman *, Satish Balakrishnan , Shashidhar Rao , Yogesh Hooda , Suyog Pol 1 Advanced Centre for Treatment, Research and Education in Cancer, Navi Mumbai, Maharashtra, India, 2 Schrodinger, New York, New York, United States of America Abstract Background: Proteases play a central role in cellular homeostasis and are responsible for the spatio- temporal regulation of function. Many putative proteases have been recently identified through genomic approaches, leading to a surge in global profiling attempts to characterize their function. Through such efforts and others it has become evident that many proteases play non-traditional roles. Accordingly, the number and the variety of the substrate repertoire of proteases are expected to be much larger than previously assumed. In line with such global profiling attempts, we present here a method for the prediction of natural substrates of endo proteases (human proteases used as an example) by employing short peptide sequences as specificity determinants. Methodology/Principal Findings: Our method incorporates specificity determinants unique to individual enzymes and physiologically relevant dual filters namely, solvent accessible surface area-a parameter dependent on protein three- dimensional structure and subcellular localization. By incorporating such hitherto unused principles in prediction methods, a novel ligand docking strategy to mimic substrate binding at the active site