TY - JOUR
T1 - Molecular docking and comparative molecular similarity indices analysis of estrogenicity of polybrominated diphenyl ethers and their analogues
AU - Yang, Weihua
AU - Liu, Xiaohua
AU - Liu, Hongling
AU - Wu, Yang
AU - Giesy, John P.
AU - Yu, Hongxia
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - Endocrine-disrupting activity
KW - Ligand-receptor interaction mechanism
KW - Receptor-based
KW - Surflex dock
KW - Three-dimensional quantitative structure-activity relationships
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U2 - 10.1002/etc.70
DO - 10.1002/etc.70
M3 - RGC 21 - Publication in refereed journal
C2 - 20821492
SN - 0730-7268
VL - 29
SP - 660
EP - 668
JO - Environmental Toxicology and Chemistry
JF - Environmental Toxicology and Chemistry
IS - 3
ER -