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

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 ²_pred = 0.686 (the test set, 6 compounds), and Q ²_EXT = 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.