Insight into the Binding Interaction between PEDCs and hERRγ Utilizing Molecular Docking and Molecular Dynamics...

Area of Science:

• Environmental Chemistry
• Molecular Biology
• Toxicology

Background:

• Phenolic environmental endocrine-disrupting chemicals (PEDCs) are prevalent contaminants.
• PEDCs pose risks to human health and ecosystems.
• Human estrogen-related receptor gamma (hERRγ) is a target for PEDC effects, but interaction mechanisms are unclear.

Purpose of the Study:

• To elucidate the atomic-level interactions between hERRγ and three specific PEDCs.
• To identify key residues and binding forces involved in hERRγ-PEDC interactions.
• To understand how PEDCs disrupt hERRγ function and contribute to health issues.

Main Methods:

• Molecular docking and multiple molecular dynamics (MD) simulations were employed.
• Binding energies were calculated using MM-PBSA and SIE methods.
• Structural analysis focused on identifying critical residues and interaction types.

Main Results:

• Detailed interaction patterns between hERRγ and PEDCs were revealed.
• Residues Leu271, Leu309, Leu345, and Phe435 are crucial for PEDC binding.
• CH-π, π-π interactions, and hydrogen bonds are major binding forces.
• Hydrophobic methoxide groups in BP(2,2)(Me) reduce binding energy.

Conclusions:

• The study clarifies the molecular interactions of PEDCs with hERRγ.
• Findings highlight specific residues and forces driving endocrine disruption.
• Results provide a foundation for understanding PEDC-induced health problems and developing mitigation strategies.