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

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Abstract

Context

Human estrogen-related receptor γ (hERRγ) is a key protein involved in various endocrines and metabolic signaling. Numerous environmental endocrine-disrupting chemicals (EDCs) can impact related physiological activities through receptor signaling pathways. Focused on hERRγ with 4-isopropylphenol, bisphenol-F (BPF), and BP(2,2)(Un) complexes, we executed molecular docking and multiple molecular dynamics (MD) simulations along with molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) and solvation interaction energy (SIE) calculation to study the detailed dynamical structural characteristics and interactions between them. Molecular docking showed that hydrogen bonds and hydrophobic interactions were the prime interactions to keep the stability of BPF-hERRγ and hERRγ-BP(2,2)(Un) complexes. Through MD simulations, we observed that all complexes reach equilibrium during the initial 50 ns of simulation, but these three EDCs lead to local structure changes in hERRγ. Energy results further identified key residues L268, V313, L345, and F435 around the binding pockets through CH-π, π-π, and hydrogen bonds interactions play an important stabilizing role in the recognition with EDCs. And most noticeable of all, hydrophobic methoxide groups in BP(2,2)(Un) is useful for decreasing the binding ability between EDCs and hERRγ. These results may contribute to evaluate latent diseases associated with EDCs exposure at the micro level and find potential substitutes.

Method

Autodock4.2 was used to conduct the molecular docking, sietraj program was performed to calculate the energy, and VMD software was used to visualize the structure. Amber18 was conducted to perform the MD simulation and other analyses.

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Data availability

The datasets can be obtained from the corresponding author, through email request, reasonable request.

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Funding

This work was supported by Fundamental Research Funds for Heilongjiang Educational Committee of Chinese hemp specialty (145209504).

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Authors and Affiliations

  1. College of Chemistry and Chemical Engineering, Qiqihar University, Qiqihar, 161006, China

    Ying Sun, Lin Chen, Bing Zhao & Ruige Wang

  2. Heilongjiang Provincial Key Laboratory of Surface Active Agent and Auxiliary, Qiqihar University, Qiqihar, 161006, China

    Bing Zhao

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  1. Ying Sun
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Contributions

Lin Chen contributed to the conception of the study and wrote the manuscript; Ying Sun performed the experiment and manuscript preparation; Bing Zhao helped perform the analysis with constructive discussions; Ruige Wang performed the data analyses and wrote the manuscript.

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Correspondence to Lin Chen or Ruige Wang.

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Sun, Y., Chen, L., Zhao, B. et al. Molecular docking and molecular dynamics simulation decoding molecular mechanism of EDCs binding to hERRγ. J Mol Model 30, 127 (2024). https://doi.org/10.1007/s00894-024-05926-z

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