title: Molecular docking and molecular dynamics studies on the interactions of hydroxylated polybrominated diphenyl ethers to estrogen receptor alpha.
abstract: Environmental estrogens have attracted great concerns. Recent studies have indicated that some hydroxylated polybrominated diphenyl ethers (HO-PBDEs) can interact with estrogen receptor (ER), and exhibit estrogenic activity. However, interactions between HO-PBDEs and ER are not well understood. In this work, molecular docking and molecular dynamics (MD) simulations were performed to characterize interactions of two HO-PBDEs (4'-HO-BDE30 and 4'-HO-BDE121) with ERα. Surflex-Dock was employed to reveal the probable binding conformations of the compounds at the active site of ERα; MD simulation was used to determine the detailed binding process. The driving forces of the binding between HO-PBDEs and ERα were van der Waals and electrostatic interactions. The decomposition of the binding free energy indicated that the hydrogen bonds between the residues Glu353, Gly521 and ligands were crucial for anchoring the ligands into the active site of ERα and stabilizing their conformations. The results showed that different interaction modes and different specific interactions with some residues were responsible for the different estrogenic activities of the two HO-PBDEs.
authors: Huazhong University of Science and Technology Wenhua College, Wuhan 430074, China.
authors: Qun
authors: Q
authors: Lu
authors: Environmental Engineering Program, Department of Civil Engineering, Auburn University, Auburn, AL 36849, USA.
authors: Zhengqing
authors: Z
authors: Cai
authors: Environmental Engineering Program, Department of Civil Engineering, Auburn University, Auburn, AL 36849, USA. Electronic address: jzf0017@auburn.edu.
authors: Jie
authors: J
authors: Fu
authors: School of Environmental and Municipal Engineering, Qingdao Technological University, Qingdao 266033, China.
authors: Siyi
authors: S
authors: Luo
authors: State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
authors: Chunsheng
authors: C
authors: Liu
authors: Yunnan Entry-Exit Inspection and Quarantine Bureau, Kunming 650228, China.
authors: Xiaolin
authors: X
authors: Li
authors: Environmental Engineering Program, Department of Civil Engineering, Auburn University, Auburn, AL 36849, USA. Electronic address: zhaodon@auburn.edu.
authors: Dongye
authors: D
authors: Zhao
mesh_terms: D047628:Estrogen Receptor alpha / Q000737:chemistry* / Q000378:metabolism; D055768:Halogenated Diphenyl Ethers / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D015203:Reproducibility of Results; D014874:Water Pollutants, Chemical / Q000737:chemistry
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D055768:Halogenated Diphenyl Ethers; D014874:Water Pollutants, Chemical
keywords: Endocrine disrupting effect; Estrogen receptor α; Hydroxylated polybrominated diphenyl ethers; Molecular modeling