Analysis of Binding Modes between Three Perfluorosulfonates and GPER Based on Computational Simulation and Multiple...

Area of Science:

• Environmental Chemistry
• Toxicology
• Molecular Biology

Background:

• Perfluorinated compounds (PFCs) are global environmental pollutants with significant toxicological implications.
• Understanding PFCs' interactions with biological systems is crucial for life sciences, environmental science, chemistry, and ecotoxicology.

Purpose of the Study:

• To investigate the impact of PFCs on the G protein-coupled estrogen receptor (GPER) under simulated human physiological conditions.
• To elucidate the molecular-level binding modes and toxicological mechanisms between PFCs and GPER.

Main Methods:

• Utilized a combination of spectroscopic techniques (fluorescence, FTIR) and computational simulations (molecular docking, molecular dynamics).
• Assessed GPER fluorescence quenching, binding constants, and protein structural changes upon PFC interaction.

Main Results:

• All three perfluorinated sulfonic acids (PFSAs) induced static quenching of GPER fluorescence with high binding affinity (10^6).
• PFSAs bind within GPER's hydrophobic cavity, forming hydrogen and hydrophobic interactions.
• PFC binding increased protein hydrophobicity, altered secondary structure, and enhanced protein stability.

Conclusions:

• PFCs exhibit strong binding affinity to GPER, impacting its structure and stability.
• This study enhances understanding of PFCs' endocrine disruption potential and human health risks.
• Findings support environmental policy, pollution monitoring, and potential therapeutic strategies.