title: Identification of SRC as a potent drug target for asthma, using an integrative approach of protein interactome analysis and in silico drug discovery.
abstract: Network-biology inspired modeling of interactome data and computational chemistry have the potential to revolutionize drug discovery by complementing conventional methods. We consider asthma, a complex disease characterized by intricate molecular mechanisms, for our study. We aim to integrate prediction of potent drug targets using graph-theoretical methods and subsequent identification of small molecules capable of modulating activity of the best target. In this work, we construct the protein interactome underlying this disease: Asthma Protein Interactome (API). Using a strategy based on network analysis of the interactome, we identify a set of potential drug targets for asthma. Topologically and dynamically, v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (SRC) emerges as the most central target in API. SRC is known to play an important role in promoting airway smooth muscle cell growth and facilitating migration in airway remodeling. From interactome analysis, and with the reported role in respiratory mechanisms, SRC emerges as a promising drug target for asthma. Further, we proceed to identify leads for SRC from a public database of small molecules. We predict two potential leads for SRC using ligand-based virtual screening methodology.
authors: Biotechnology Division, Institute of Himalayan Bioresource Technology, Council of Scientific and Industrial Research (CSIR-IHBT), Palampur, India.
authors: Vinay
authors: V
authors: Randhawa
authors: Ganesh
authors: G
authors: Bagler
mesh_terms: D000465:Algorithms; D018927:Anti-Asthmatic Agents / Q000737:chemistry*; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D020134:Catalytic Domain; D003198:Computer Simulation; D055808:Drug Discovery / Q000379:methods*; D056726:Genetic Association Studies; D006801:Humans; D008954:Models, Biological; D062105:Molecular Docking Simulation; D015688:Oncogene Protein pp60(v-src) / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011485:Protein Binding; D025941:Protein Interaction Mapping; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D020543:Proteome / Q000737:chemistry; D012372:ROC Curve; D013499:Surface Properties
chemical_list: D018927:Anti-Asthmatic Agents; D047428:Protein Kinase Inhibitors; D020543:Proteome; D015688:Oncogene Protein pp60(v-src)