title: Molecular modeling and molecular dynamics simulation studies on the interactions of hydroxylated polychlorinated biphenyls with estrogen receptor-β.
abstract: Endocrine-disrupting chemicals have attracted great concern. As major metabolites of polychlorinated biphenyls (PCBs), hydroxylated polychlorinated biphenyls (HO-PCBs) may disrupt estrogen hormone status because of their structural similarity to estrogen endogenous compounds. However, interactions between HO-PCBs and estrogen receptors (ERs) are not fully understood. In the present work, a molecular modeling study combining molecular docking, molecular dynamics simulations, and binding free energy calculations was performed to characterize the interactions of three HO-PCBs (4'-HO-PCB50, 2'-HO-PCB65, and 4'-HO-PCB69) having much different estrogenic activities with ERβ. Docking results showed that binding between ligands and ERβ was stabilized by hydrogen bond and hydrophobic interactions. The binding free energies of three ligands with ERβ were calculated, and further binding free energy decomposition analysis indicated that the dominating driving force of the binding between the ligands and ERβ was the van der Waals interaction. Some key residues, such as Leu298, Phe356, Gly472, His475, and Leu476, played important roles in ligand-receptor interactions by forming hydrophobic and hydrogen bond interactions with ligands. The results may be beneficial to increase understanding of the interactions between HO-PCBs and ERβ.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210046, People's Republic of China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
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: D052244:Endocrine Disruptors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004785:Environmental Pollutants / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D006900:Hydroxylation; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011078:Polychlorinated Biphenyls / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D047629:Estrogen Receptor beta; D008024:Ligands; D004958:Estradiol; D011078:Polychlorinated Biphenyls