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Molecular docking and comparative molecular similarity indices analysis of estrogenicity of polybrominated diphenyl ethers and their analogues

Authors

  • Weihua Yang,

    1. State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, China
    2. School of Chemistry and Chemical Engineering, Xuzhou Normal University, Xuzhou 221116, China
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  • Xiaohua Liu,

    1. State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, China
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  • Hongling Liu,

    1. State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, China
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  • Yang Wu,

    1. State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, China
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  • John P. Giesy,

    1. State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, China
    2. Department of Biomedical and Veterinary Biosciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5A2, Canada
    3. Zoology Department, National Food Safety and Toxicology Center, and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824, USA
    4. Biology and Chemistry Department, City University of Hong Kong, Kowloon, Hong Kong Special Administrative Region, China
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  • Hongxia Yu

    Corresponding author
    1. State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, China
    • State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093, China.
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Abstract

Molecular docking and three-dimensional quantitative structure–activity relationships (3D-QSAR) were used to develop models to predict estrogenicity of polybrominated diphenyl ethers (PBDEs), para-hydroxylated polybrominated diphenyl ethers (para-HO-PBDEs), and brominated bisphenol A compounds to the human estrogen receptor α (hERα). Based on the molecular conformations developed from the molecular docking, predictive comparative molecular similarity indices analysis (CoMSIA) models were developed. The results of CoMSIA modeling with region focusing included were: leave-one-out (LOO) cross-validated coefficient q2(LOO) = 0.722 (all 26 compounds), q2(LOO) = 0.633 (the training set, 20 compounds), q2(LMO, two groups) = 0.520 ± 0.155 (26 compounds), q2(LMO, five groups) = 0.665 ± 0.068 (26 compounds), predictive r2, r2pred = 0.686 (the test set, 6 compounds), and Q2EXT = 0.678. The 3D-QSAR can be used to infer the activities of compounds with similar structural characteristics. The interaction mechanism between compounds and the hERα was explored. Hydrogen bonding of the compound with Glu353 in the hERα is an important determinant of the estrogenic activity of para-HO-PBDEs and brominated bisphenol A. Environ. Toxicol. Chem. 2010;29:660–668. © 2009 SETAC

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