Molecular docking and molecular dynamics simulation decoding molecular mechanism of EDCs binding to hERRγ

Area of Science:

• Biochemistry
• Molecular Biology
• Environmental Science

Background:

• Human estrogen-related receptor γ (hERRγ) is crucial in endocrine and metabolic signaling.
• Environmental endocrine-disrupting chemicals (EDCs) can disrupt physiological activities via receptor pathways.

Purpose of the Study:

• To investigate the molecular interactions between hERRγ and EDCs like 4-isopropylphenol, bisphenol-F (BPF), and BP(2,2)(Un).
• To analyze the structural dynamics and binding characteristics of these complexes using computational methods.

Main Methods:

• Molecular docking using Autodock4.2.
• Molecular dynamics (MD) simulations using Amber18.
• MM-PBSA and SIE calculations for energy analysis.
• Structure visualization with VMD software.

Main Results:

• Hydrogen bonds and hydrophobic interactions stabilize BPF-hERRγ and hERRγ-BP(2,2)(Un) complexes.
• All three EDCs induced local structural changes in hERRγ.
• Key residues (L268, V313, L345, F435) were identified as important for EDC binding.
• Hydrophobic methoxide groups in BP(2,2)(Un) reduced binding affinity.

Conclusions:

• Detailed molecular insights into hERRγ-EDC interactions.
• Understanding EDC-induced structural changes in hERRγ.
• Potential for evaluating EDC-related diseases and identifying safer alternatives.