title: In silico study on hydroxylated polychlorinated biphenyls as androgen receptor antagonists.
abstract: Hydroxylated polychlorinated biphenyls (HO-PCBs), major metabolites of PCBs, may have the potential to disrupt androgen hormone homeostasis. However, there is a lack of systematic investigation into the intermolecular interaction mechanism between HO-PCBs and the androgen receptor (AR). In this study, the combination of three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, and molecular dynamics (MD) simulations was performed to elucidate structural characteristics that influence the anti-androgen activity of HO-PCBs, and to provide a better understanding of the binding modes between HO-PCBs and AR. A predictive comparative molecular field analysis (CoMFA) model was developed with good robustness and predictive ability. Graphical interpretation of the model provided some insights into the structural features that affect the anti-androgen activity of HO-PCBs. The hydrogen bond interaction with Gln711, and hydrophobic interactions with residues in the hydrophobic pocket played important roles in the binding of ligand with receptor. These results are expected to be beneficial to predict anti-androgen activities of other HO-PCBs and provided possible clues for further elucidation of the binding mechanism of HO-PCBs with AR.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Hongling
authors.initials: H
authors.lastname: Liu
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Liu
authors.forename: Xiangping
authors.initials: X
authors.lastname: Qian
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yu
mesh_terms: D000726:Androgen Antagonists / Q000737:chemistry / Q000378:metabolism; D059002:Androgen Receptor Antagonists / Q000737:chemistry / Q000633:toxicity*; D003198:Computer Simulation; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D006900:Hydroxylation; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000633:toxicity*; D021281:Quantitative Structure-Activity Relationship; D011944:Receptors, Androgen / Q000737:chemistry / Q000378:metabolism
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D008024:Ligands; D011944:Receptors, Androgen; D011078:Polychlorinated Biphenyls