title: Molecular docking, molecular dynamics simulation, and structure-based 3D-QSAR studies on the aryl hydrocarbon receptor agonistic activity of hydroxylated polychlorinated biphenyls.
abstract: The binding interactions between hydroxylated polychlorinated biphenyls (HO-PCBs) and the aryl hydrocarbon receptor (AhR) are suspected of causing toxic effects. To understand the binding mode between HO-PCBs and AhR, and to explore the structural characteristics that influence the AhR agonistic activities of HO-PCBs, the combination of molecular docking, three-dimensional quantitative structure-activity relationship (3D-QSAR), and molecular dynamics (MD) simulations was performed. Using molecular docking, the HO-PCBs were docked into the binding pocket of AhR, which was generated by homology modeling. Comparative molecular similarity index analysis (CoMSIA) models were subsequently developed from three different alignment rules. The optimum 3D-QSAR model showed good predictive ability (q(2)=0.583, R(2)=0.913) and good mechanism interpretability. The statistical reliability of the CoMSIA model was also validated. In addition, molecular docking and MD simulations were applied to explore the binding modes between the ligands and AhR. The results obtained from this study may lead to a better understanding of the interaction mechanism between HO-PCBs and AhR.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
authors.forename: Fu
authors.initials: F
authors.lastname: Cao
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.affiliation: Suzhou NeuPharma Co., Ltd., Suzhou 215123, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China. Electronic address: fanfan_67946@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Suzhou NeuPharma Co., Ltd., Suzhou 215123, China; College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
authors.forename: Xiangping
authors.initials: X
authors.lastname: Qian
authors.affiliation: Suzhou NeuPharma Co., Ltd., Suzhou 215123, China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China. Electronic address: hongxiayu01@yahoo.com.cn.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D001665:Binding Sites; D003196:Computer Graphics; D006801:Humans; D006900:Hydroxylation; D008024:Ligands; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon; D011078:Polychlorinated Biphenyls
keywords: 3D-QSAR; Ah receptor; HO-PCBs; Molecular docking; Molecular dynamics