title: Identification of key nodes of type 2 diabetes mellitus protein interactome and study of their interactions with phloridzin.
abstract: Network biology-inspired approaches could be used effectively in probing regulatory processes by which small molecules intervene with disease mechanisms. The present study aims at identification of key targets of type 2 diabetes mellitus (T2DM) by network analysis of the underlying protein interactome, and probing for mechanisms by which phloridzin could be critical at altering the disease phenotype. Towards this goal, we constructed a protein-protein interaction network associated with T2DM, starting from candidate genes and systems-level interactions data available. The relevance of the network constructed was verified with the help of gene ontology, node deletion, and biological essentiality studies. Using a network analysis method, MAPK1, EP300, and SMAD2 were identified as the most central proteins of potential therapeutic value. Phloridzin, a known antidiabetic agent, potentially interacts with proteins central to T2DM mechanisms. The structural understanding of interaction of phloridzin with these proteins of relevance to T2DM could provide better insight into its regulatory mechanisms and help in developing better therapeutic agents. The molecular docking results suggest that phloridzin is potentially involved in making critical interactions with MAPK1. These results could further be validated by experimental studies and could be used to design therapeutic agents for T2DM intervention.
authors.affiliation: Biotechnology Division, Institute of Himalayan Bioresource Technology, Council of Scientific and Industrial Research (CSIR-IHBT), Palampur, India.
authors.forename: Vinay
authors.initials: V
authors.lastname: Randhawa
authors.forename: Purnima
authors.initials: P
authors.lastname: Sharma
authors.forename: Shashi
authors.initials: S
authors.lastname: Bhushan
authors.forename: Ganesh
authors.initials: G
authors.lastname: Bagler
mesh_terms: D001665:Binding Sites; D019295:Computational Biology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000737:chemistry / Q000378:metabolism; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D058977:Molecular Sequence Annotation; D010695:Phlorhizin / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D051899:Smad2 Protein / Q000737:chemistry / Q000378:metabolism
chemical_list: D020543:Proteome; D051899:Smad2 Protein; D010695:Phlorhizin; D050881:E1A-Associated p300 Protein; D019950:Mitogen-Activated Protein Kinase 1