title: Predictive insight into the relationship between AhR binding property and toxicity of polybrominated diphenyl ethers by PLS-derived QSAR.
abstract: Polybrominated diphenyl ethers (PBDEs) are experimentally indicated to be capable of binding to the cytosolic aryl hydrocarbon receptor (AhR) and show a weak or moderate toxicity. However, little is yet known about the AhR-mediated toxicology. To fully evaluate the structural effects of PBDE ligand on AhR binding affinity and toxicity, quantitative structure-activity relationships (QSARs) were developed by PLS analysis. In this study, a simple but potent QSAR that was qualified with much better or comparable performance of prediction was optimally established for PBDE toxicity. With QSAR analysis, the AhR binding property was carefully described to reflect the origin of AhR binding affinity. Besides the effects from topological characters, the dispersion and electrostatic interactions were of indispensability for AhR binding affinity whereas the dispersion was further suggested to be dominant. The structural requirement for AhR binding affinity and toxicity was also investigated. As was similarly observed for polychlorinated biphenyls (PCBs), the preferential bromination at para- and meta (particularly 3,3'-)-sites was confirmed as a key determinant to improve the AhR binding affinity and the toxicity of PBDEs.
authors: State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, PR China.
authors: Chenggang
authors: C
authors: Gu
authors: Mohammad
authors: M
authors: Goodarzi
authors: Xinglun
authors: X
authors: Yang
authors: Yongrong
authors: Y
authors: Bian
authors: Cheng
authors: C
authors: Sun
authors: Xin
authors: X
authors: Jiang
mesh_terms: D055768:Halogenated Diphenyl Ethers / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000378:metabolism*
chemical_list: D055768:Halogenated Diphenyl Ethers; D018336:Receptors, Aryl Hydrocarbon