title: Docking studies of antidepressants against single crystal structure of tryptophan 2, 3-dioxygenase using Molegro Virtual Docker software.
abstract: Tryptophan 2, 3-dioxygenase (TDO) a heme containing enzyme found in mammalian liver is responsible for tryptophan (Trp) catabolism. Trp is an essential amino acid that is degraded in to N-formylkynurenine by the action of TDO. The protein ligand interaction plays a significant role in structural based drug designing. The current study illustrates the binding of established antidepressants (ADs) against TDO enzyme using in-silico docking studies. For this purpose, Fluoxetine, Paroxetine, Sertraline, Fluvoxamine, Seproxetine, Citalopram, Moclobamide, Hyperforin and Amoxepine were selected. In-silico docking studies were carried out using Molegro Virtual Docker (MVD) software. Docking results show that all ADs fit well in the active site of TDO moreover Hyperforin and Paroxetine exhibited high docking scores of -152.484k cal/mol and -139.706k cal/mol, respectively. It is concluded that Hyperforin and Paroxetine are possible lead molecules because of their high docking scores as compared to other ADs examined. Therefore, these two ADs stand as potent inhibitors of TDO enzyme.
authors.affiliation: Clinical Biochemistry and Psychopharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi, Pakistan.
authors.forename: Shazia
authors.initials: S
authors.lastname: Dawood
authors.affiliation: National Centre for Proteomics, University of Karachi, Karachi, Pakistan.
authors.forename: Shamshad
authors.initials: S
authors.lastname: Zarina
authors.affiliation: Clinical Biochemistry and Psychopharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi, Pakistan.
authors.forename: Samina
authors.initials: S
authors.lastname: Bano
mesh_terms: D000928:Antidepressive Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011487:Protein Conformation; D012984:Software; D013329:Structure-Activity Relationship; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D014366:Tryptophan Oxygenase