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

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 (hERalpha). In this study a docking study was carried out to explore the binding modes of PBDE compounds as hERalpha 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 17beta-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 hERalpha can help to screen out antiestrogenic compounds and further develop descriptive and predictive models in ecotoxicology.