Exploring the binding features of polybrominated diphenyl ethers as estrogen receptor antagonists: docking studies

Abstract

The polybrominated diphenyl ethers (PBDEs) accumulating in nature are known to be endocrine-disrupting compounds. Of first concern are those interacting with and altering activity of the human estrogen receptor alpha (hERα). In this study a docking study was carried out to explore the binding modes of PBDE compounds as hERα antagonists. It was found that some of the PBDE compounds with antiestrogenic activity extended into the channel of the estrogen receptor (ER), which is usually occupied by the alkylamine side chain of the ER antagonists raloxifene (RAL) and 4-hydroxytamoxifen (OHT), while most PBDE compounds without antiestrogenic activity adopted binding modes similar to that of ER agonist 17β-estradiol (E2), located in the binding cavity and which did not protrude into the channel. The present study suggests that pose comparison based on docking is useful for discriminating whether or not PBDE compounds have antiestrogenic activity. Knowing the binding modes of compounds in hERα can help to screen out antiestrogenic compounds and further develop descriptive and predictive models in ecotoxicology.

Keywords:

• endocrine-disruptors
• human estrogen receptor alpha (hERα)
• antiestrogenicity
• molecular docking

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant 20737001, 20977047) and the 863 Program of China (Grant 2006AA06Z424).