Study on the estrogenic activity of polybrominated diphenyl ethers and novel brominated flame retardants: analysis based on the receptor interaction mechanism of molecular docking

Polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (OH-PBDEs) can disrupt endocrine function by binding to estrogen receptor α (ERα), while the estrogenic activity of novel brominated flame retardants (NBFRs) has not yet been systematically evaluated. In this study, molecular docking is conducted using AutoDock (version 1.5.6) to explore the interaction of PBDEs, OH-PBDEs, and NBFRs with human estrogen receptor alpha (hERα). The findings suggest the combination of PBDEs and NBFR with the ERα site focuses on two distinct pockets. These two pockets are similar to the binding sites of the existing typical environmental estrogens E2 and OHT. The key residues are LEU346, GLU353, ARG394, HIS524 and PRO324, LEU327, GLU353, TRP393, LYS449 respectively. Among the homologs of PBDEs, BDE86 has the highest binding energy, reaching −9.05 kcal/mol. For BDE85, hydroxylation retains the binding site while facilitating a hydrogen bond between the ligand and PRO325. This structural feature enhances the absolute binding energy, with the values shifting from −7.79 kcal/mol to −7.99 kcal/mol upon hydroxylation. The binding sites of TBB and TBECH are the same as those of low - brominated PBDEs, and they may have an agonist effect. The binding sites of PBEB, TBBPA, and BTBPE are the same as those of high-brominated PBDEs, and they may have an antagonist effect.