title: Computational prediction of a putative binding site on drp1: implications for antiparkinsonian therapy.
abstract: Parkinson's disease is the second most common neurodegenerative disorder, for which no cure or disease-modifying therapies exist. It is evident that mechanisms impairing mitochondrial dynamics will damage cell signaling pathways, leading to neuronal death that manifests as Parkinson's disease. Dynamin related protein1, a highly conserved profission protein that catalyzes the process of mitochondrial fission, is also associated with the excessive fragmentation of mitochondria, impaired mitochondrial dynamics and cell death. Hence, Dynamin related protein1 has emerged as a key therapeutic target for diseases involving mitochondrial dysfunction. In this work, we employed a relatively novel and integrated computational strategy to identify a cryptic binding site of Dynamin related protein1 and exploited the predicted site in the rational drug designing process. This novel approach yielded three potential inhibitors, and all of them were evaluated for their neuroprotective efficacy in C. elegans model of Parkinson's disease.
authors: School of Biotechnology, National Institute of Technology Calicut , Calicut 673601, Kerala, India.
authors: Hanumanthappa
authors: H
authors: Pradeep
authors: G Krishnamurthy
authors: GK
authors: Rajanikant
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000187:drug effects; D015195:Drug Design; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009154:Mutation; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy*; D011487:Protein Conformation
chemical_list: D000978:Antiparkinson Agents; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D018696:Neuroprotective Agents; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins