title: The exploration of network motifs as potential drug targets from post-translational regulatory networks.
abstract: Phosphorylation and proteolysis are among the most common post-translational modifications (PTMs), and play critical roles in various biological processes. More recent discoveries imply that the crosstalks between these two PTMs are involved in many diseases. In this work, we construct a post-translational regulatory network (PTRN) consists of phosphorylation and proteolysis processes, which enables us to investigate the regulatory interplays between these two PTMs. With the PTRN, we identify some functional network motifs that are significantly enriched with drug targets, some of which are further found to contain multiple proteins targeted by combinatorial drugs. These findings imply that the network motifs may be used to predict targets when designing new drugs. Inspired by this, we propose a novel computational approach called NetTar for predicting drug targets using the identified network motifs. Benchmarking results on real data indicate that our approach can be used for accurate prediction of novel proteins targeted by known drugs.
authors: Department of Computer Science and Technology, School of Electronics and Information Engineering, Tongji University, Shanghai 201804, China.|Shanghai Water (Ocean) Administrative Service Center, Shanghai 200050, China.
authors: Xiao-Dong
authors: XD
authors: Zhang
authors: Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.|Department of Biochemistry and Molecular Biology, Faculty of Medicine, Monash University, Melbourne, VIC 3800, Australia.
authors: Jiangning
authors: J
authors: Song
authors: European Molecular Biology Laboratory, Meyerhofstraße 1, Heidelberg 69117, Germany.
authors: Peer
authors: P
authors: Bork
authors: Department of Computer Science and Technology, School of Electronics and Information Engineering, Tongji University, Shanghai 201804, China.
authors: Xing-Ming
authors: XM
authors: Zhao
mesh_terms: D019295:Computational Biology; D016208:Databases, Factual; D015195:Drug Design; D008962:Models, Theoretical; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D011506:Proteins