Docking studies of antidepressants against single crystal structure of tryptophan 2, 3-dioxygenase using Molegro Virtual Docker software

Pak J Pharm Sci. 2014 Sep;27(5 Spec no):1529-39.

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.

MeSH terms

  • Antidepressive Agents / chemistry
  • Antidepressive Agents / metabolism
  • Antidepressive Agents / pharmacology*
  • Binding Sites
  • Catalytic Domain
  • Drug Design*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Molecular Docking Simulation*
  • Molecular Structure
  • Protein Conformation
  • Software*
  • Structure-Activity Relationship
  • Tryptophan Oxygenase / antagonists & inhibitors*
  • Tryptophan Oxygenase / chemistry
  • Tryptophan Oxygenase / metabolism

Substances

  • Antidepressive Agents
  • Enzyme Inhibitors
  • Tryptophan Oxygenase