Binding interactions of halogenated bisphenol A with mouse PPARα: In vitro investigation and molecular dynamics simulation. (February 2018)

• Record Type: Journal Article
• Authors: Zhang, Jie; Li, Tiezhu; Wang, Tuoyi; Guan, Tianzhu; Yu, Hansong; Li, Zhuolin; Wang, Yongzhi; Wang, Yongjun; Zhang, Tiehua
• Is Part Of: Toxicology letters. Volume 283(2018)
• Page Start: 32
• Page End: 38
• Publication Date: 2018-02
• Subjects: Fluorescence polarization -- Electrostatic potential -- Molecular docking -- Halogenated bisphenol A -- Peroxisome proliferator-activated receptor α; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2017.11.004
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: Interaction of halogenated BPAs with mPPARα-LBD* was investigated. Halogenated BPAs are affinity ligands for mPPARα-LBD*. The electronic properties varied with the halogenation patterns. The binding modes were illustrated by molecular docking. This work can be used for preliminary screening of halogenated BPAs. Abstract: The binding of bisphenol A (BPA) and its halogenated derivatives (halogenated BPAs) to mouse peroxisome proliferator-activated receptor α ligand binding domain (mPPARα-LBD) was examined by a combination of in vitro investigation and in silico simulation. Fluorescence polarization (FP) assay showed that halogenated BPAs could bind to mPPARα-LBD* as the affinity ligands. The calculated electrostatic potential (ESP) illustrated the different charge distributions of halogenated BPAs with altered halogenation patterns. As electron-attracting substituents, halogens decrease the positive electrostatic potential and thereby have a significant influence on the electrostatic interactions of halogenated BPAs with mPPARα-LBD*. The docking results elucidated that hydrophobic and hydrogen-bonding interactions may also contribute to stabilize the binding of the halogenated BPAs to their receptor molecule. Comparison of the calculated binding energies with the experimentally determined affinities yielded a good correlation (R 2 = 0.6659) that could provide a rational basis for designing environmentally benign chemicals with reduced toxicities. This work can potentially be used for preliminary screening of halogenated BPAs.