title: In vitro and in silico assessment of the structure-dependent binding of bisphenol analogues to glucocorticoid receptor.
abstract: Widespread use of bisphenol A (BPA) and other bisphenol analogues has attracted increasing attention for their potential adverse effects. As environmental endocrine-disrupting compounds (EDCs), bisphenols (BPs) may activate a variety of nuclear receptors, including glucocorticoid receptor (GR). In this work, the binding of 11 BPs to GR was investigated by fluorescence polarization (FP) assay in combination with molecular dynamics simulations. The human glucocorticoid receptor was prepared as a soluble recombinant protein. A fluorescein-labeled dexamethasone derivative (Dex-fl) was employed as tracer. Competitive displacement of Dex-fl from GR by BPs showed that the binding affinities of bisphenol analogues were largely dependent on their characteristic functional groups. In order to further understand the relationship between BPs structures and their GR-mediated activities, molecular docking was utilized to explore the binding modes at the atomic level. The results confirmed that structural variations of bisphenol analogues contributed to different interactions of BPs with GR, potentially causing distinct toxic effects. Comparison of the calculated binding energies vs. experimental binding affinities yielded a good correlation (R2= 0.8266), which might be helpful for the design of environmentally benign materials with reduced toxicities. In addition, the established FP assay based on GR exhibited the potential to offer an alternative to traditional methods for the detection of bisphenols.
authors.affiliation: College of Food Science and Engineering, Jilin Agricultural University, No. 2888 Xincheng Street, Changchun, Jilin, 130118, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, China.
authors.forename: Tiehua
authors.initials: T
authors.lastname: Zhang
authors.affiliation: College of Food Science and Engineering, Jilin University, Changchun, Jilin, 130062, China.
authors.forename: Tianzhu
authors.initials: T
authors.lastname: Guan
authors.affiliation: College of Food Science and Engineering, Jilin Agricultural University, No. 2888 Xincheng Street, Changchun, Jilin, 130118, China. yuhansong@jlau.edu.cn.
authors.forename: Hansong
authors.initials: H
authors.lastname: Yu
authors.affiliation: College of Food Science and Engineering, Jilin Agricultural University, No. 2888 Xincheng Street, Changchun, Jilin, 130118, China. tiezhu_li@163.com.
authors.forename: Tiezhu
authors.initials: T
authors.lastname: Li
mesh_terms: D001559:Benzhydryl Compounds / Q000378:metabolism*; D003198:Computer Simulation; D005454:Fluorescence Polarization; D066298:In Vitro Techniques; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010636:Phenols / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; D011965:Receptors, Glucocorticoid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol analogues; Fluorescence polarization; Glucocorticoid receptor; Molecular docking