Mechanisms of interaction between persistent organic pollutants (POPs) and CYP2B6: An in silico approach

Chemosphere. 2016 Sep;159:113-125. doi: 10.1016/j.chemosphere.2016.05.049. Epub 2016 Jun 7.


Human Cytochrome P450s (CYP450) are a group of heme-containing metalloenzymes responsible for recognition and metabolism of numerous xenobiotics, including drugs and environmental contaminants. CYP2B6, a member of CYP450, is well known for being a highly inducible and polymorphic enzyme and for its important role in the oxidative metabolism of environmental pollutants, such as the Polybrominated Diphenyl Ethers (PBDEs) and Polychlorinated Biphenyls (PCBs). However the mechanisms of interaction of PBDEs and PCBs with CYP2B6 is not entirely known. In this work, a computational approach was carried out to study the interactions of 41 POPs (17 PBDEs, 17 PCBs, and 7 Dioxins) with four CYP2B6 protein structures downloaded from PDB data base (PDB: 3UA5, 3QOA, 3QU8 and 4I91) using molecular docking protocols with AutoDock Vina. The best binding affinity values (kcal/mol) were obtained for PBDE-99 (-8.5), PCB-187 (-9.6), and octachloro-dibenzo-dioxin (-9.8) that can be attributed to the hydrophobic interactions with important residues, such as Phe-363, in the catalytic site of CYP2B6. Molecular docking validation revealed the best values for PDB: 3UA5 (R = 0.622, p = 0.001) demonstrating the reliability of molecular docking predictions. The information obtained in this work can be useful in evaluating the modes of interaction of xenobiotic compounds with the catalytic site of CYP2B6 and provide insights on the important role of these enzymes in the metabolism of potentially toxic compounds in humans.

Keywords: AutoDock Vina; Environmental pollutant; Molecular docking; Xenobiotic.

MeSH terms

  • Cytochrome P-450 CYP2B6 / metabolism*
  • Dioxins / metabolism*
  • Environmental Pollutants / metabolism*
  • Halogenated Diphenyl Ethers / metabolism*
  • Humans
  • Molecular Docking Simulation
  • Polychlorinated Biphenyls / metabolism*
  • Reproducibility of Results


  • Dioxins
  • Environmental Pollutants
  • Halogenated Diphenyl Ethers
  • Polychlorinated Biphenyls
  • Cytochrome P-450 CYP2B6