An ERβ electrochemical nano-receptor sensor for comparative analysis of estrogenic ligands: electrochemical responses and molecular recognition.

Estrogen plays essential roles in female physiological regulation, and its biological effects are primarily mediated through interactions with estrogen receptors. Excessive exposure to estrogenic compounds and their analogs may cause adverse biological effects and pose potential risks to human health. Therefore, elucidating the molecular recognition mechanisms between estrogen receptor β (ERβ) and estrogenic ligands is of great importance. In this study, an ERβ electrochemical nano-receptor sensor based on an Au-MoS₂/NiO nanocomposite was constructed for the quantitative determination of ten estrogenic compounds. To complement the electrochemical investigation, molecular docking and molecular dynamics simulations were employed to investigate the interaction mechanisms between ERβ and ligand molecules. The electrochemical measurements revealed ligand-dependent response characteristics, with synthetic estrogenic compounds generally producing stronger electrochemical responses than natural estrogens. The apparent electrochemical response constants (Ka) derived from electrochemical response fitting ranged from 5.63 × 10⁻16 to 3.08 × 10⁻14 mol/L. The computational analyses suggested that key amino acid residues (Leu339, Arg346, and His475) and phenolic groups of ligands contributed to ERβ-mediated molecular recognition. This study integrates receptor-mediated electrochemical sensing with molecular docking and molecular dynamics simulations to establish an experimental-computational framework for comparative investigation of ERβ-ligand recognition mechanisms among structurally diverse estrogenic compounds.