Insight into the Binding Interaction between PEDCs and hERRγ Utilizing Molecular Docking and Molecular Dynamics Simulations.
Molecules
; 29(14)2024 Jul 10.
Article
en En
| MEDLINE
| ID: mdl-39064835
ABSTRACT
Phenolic environmental endocrine-disrupting chemicals (PEDCs) are persistent EDCs that are widely found in food packaging materials and environmental media and seriously threaten human health and ecological security. Human estrogen-related receptor γ (hERRγ) has been proposed as a mediator for the low-dose effects of many environmental PEDCs; however, the atomic-level descriptions of dynamical structural features and interactions of hERRγ and PEDCs are still unclarified. Herein, how three PEDCs, 4-(1-methylpropyl)phenol (4-sec-butylphenol), 5,6,7,8-tetrahydro-2-naphthol (tetrahydro-2-napthol), and 2,2-bis(4-hydroxy-3,5-dimethoxyphenyl)propane (BP(2,2)(Me)), interact with hERRγ to produce its estrogenic disruption effects was studied. Molecular docking and multiple molecular dynamics (MD) simulations were first conducted to distinguish the detailed interaction pattern of hERRγ with PEDCs. These binding structures revealed that residues around Leu271, Leu309, Leu345, and Phe435 are important when binding with PEDCs. Furthermore, the binding energies of PEDCs with hERRγ were also characterized using the molecular mechanics/Poisson Boltzmann surface area (MM-PBSA) and solvated interaction energy (SIE) methods, and the results showed that the interactions of CH-π, π-π, and hydrogen bonds are the major contributors for hERRγ binding to these three PEDCs. What is striking is that the methoxide groups of BP(2,2)(Me), as hydrophobic groups, can help to reduce the binding energy of PEDCs binding with hERRγ. These results provide important guidance for further understanding the influence of PEDCs on human health problems.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Unión Proteica
/
Disruptores Endocrinos
/
Simulación de Dinámica Molecular
/
Simulación del Acoplamiento Molecular
Límite:
Humans
Idioma:
En
Revista:
Molecules
Asunto de la revista:
BIOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Suiza