Molecular interactions between halogenated bisphenol compounds and GPER: Spectroscopic, molecular simulation, and DFT...

Area of Science:

• Environmental Science
• Toxicology
• Molecular Biology

Background:

• Halogenated bisphenols (HBPs) are persistent environmental contaminants found globally.
• Their halogen substituents increase persistence and potential toxicity, necessitating research into cellular effects.
• Understanding interactions with receptors like GPER is crucial for human health risk evaluation.

Purpose of the Study:

• To comprehensively characterize the binding patterns and interaction mechanisms of HBPs with GPER.
• To elucidate how HBPs binding affects GPER structure and cellular responses.
• To provide insights into the health risks posed by HBPs.

Main Methods:

• Integrated approach combining multispectral analysis, molecular dynamics (MD) simulations, and quantum chemical calculations.
• Fourier-transform infrared (FT-IR) and 3D fluorescence spectroscopy.
• Stern-Volmer analysis and Density Functional Theory (DFT) calculations.

Main Results:

• Hydrogen bonding and van der Waals forces are primary GPER-HBPs binding mediators.
• Binding affinity depends on halogen count and bridging groups.
• HBPs induce significant GPER structural changes, including altered secondary structure (reduced β-sheet content).
• Static quenching is the dominant fluorescence quenching mechanism.

Conclusions:

• HBPs interact with GPER through specific binding modes and sites, driven by hydrogen bonds, halogen bonds, and electrostatic interactions.
• HBPs binding causes substantial GPER structural and functional modifications.
• These findings enhance the assessment of health risks associated with HBPs exposure.