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Structure–activity relationship study on the binding of PBDEs with thyroxine transport proteins
Author(s) -
Yang Weihua,
Shen Shide,
Mu Lailong,
Yu Hongxia
Publication year - 2011
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1002/etc.645
Subject(s) - loo , polybrominated diphenyl ethers , diphenyl ether , chemistry , quantitative structure–activity relationship , hydrogen bond , amino acid residue , stereochemistry , computational chemistry , molecule , biochemistry , organic chemistry , peptide sequence , pollutant , gene
Molecular docking and three‐dimensional quantitative structure–activity relationships (3D‐QSAR) were used to develop models to predict binding affinity of polybrominated diphenyl ether (PBDE) compounds to the human transthyretin (TTR). Based on the molecular conformations derived from the molecular docking, predictive comparative molecular similarity indices analysis (CoMSIA) models were developed. The results of CoMSIA models were as follows: leave‐one‐out (LOO) cross‐validated squared coefficient q 2 (LOO) = 0.827 (full model, for all 28 compounds); q 2 (LOO) = 0.752 (split model, for 22 compounds in the training set); leave‐many‐out (LMO) cross‐validated squared coefficient q 2 (LMO, two groups) = 0.723 ± 0.100 (full model, for all 28 compounds); q 2 (LMO, five groups) = 0.795 ± 0.030 (full model, for all 28 compounds); and the predictive squared correlation coefficient r 2 pred = 0.928 (for six compounds in the test set). The developed CoMSIA models can be used to infer the activities of compounds with similar structural characteristics. In addition, the interaction mechanism between hydroxylated polybrominated diphenyl ethers (HO‐PBDEs) and the TTR was explored. Hydrogen bonding with amino acid residues Asp74, Ala29, and Asn27 may be an important determinant for HO‐PBDEs binding to TTR. Among them, forming hydrogen bonds with amino acid residues Asp74 might exert a more important function. Environ. Toxicol. Chem. 2011;30:2431–2439. © 2011 SETAC