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

Weihua Yang, Xiaohua Liu, Hongling Liu, Yang Wu, John P. Giesy, Hongxia Yu

    Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

    18 Citations (Scopus)

    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, r 2pred = 0.686 (the test set, 6 compounds), and Q 2EXT = 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. © 2009 SETAC.
    Original languageEnglish
    Pages (from-to)660-668
    JournalEnvironmental Toxicology and Chemistry
    Volume29
    Issue number3
    DOIs
    Publication statusPublished - 2010

    Research Keywords

    • Endocrine-disrupting activity
    • Ligand-receptor interaction mechanism
    • Receptor-based
    • Surflex dock
    • Three-dimensional quantitative structure-activity relationships

    Fingerprint

    Dive into the research topics of 'Molecular docking and comparative molecular similarity indices analysis of estrogenicity of polybrominated diphenyl ethers and their analogues'. Together they form a unique fingerprint.

    Cite this