G-protein-coupled receptors (GPCRs) are integral membrane proteins that mediate critical physiological processes by translating extracellular signals into intracellular responses. Among them, the β2-Adrenergic Receptor (β2-AR) plays a significant role in smooth-muscle relaxation, bronchodilation, and cardiovascular regulation, making it a primary target for treating conditions such as asthma, hypertension, and chronic obstructive pulmonary disease (COPD) [1]. While synthetic drugs are widely used to target β2-AR, they often lead to adverse effects and drug resistance, necessitating the exploration of alternative therapeutic approaches [2].

This study utilized molecular docking methods with AutoDock 4.6 to investigate the interactions of natural compounds, including ephedrine, quercetin, catechin, and resveratrol, with β2-AR. The receptor's 3D structure was retrieved from the Protein Data Bank (PDB ID: 2RH1) [3], and docking studies evaluated the binding energies, hydrogen bonding, and other stabilizing interactions between the ligands and the receptor's active site. Ephedrine was observed to form hydrogen bonds with key residues, consistent with previous studies [4]. Quercetin exhibited strong binding interactions with the β2-AR's active site, confirming its potential as a natural inhibitor [5].

These findings highlight the promise of natural compounds in modulating GPCR activity, particularly β2-AR, as safe and effective alternatives to synthetic drugs. The application of computational methods like molecular docking further emphasizes their utility in identifying bio-inspired strategies for drug discovery targeting GPCR-related diseases.

References

[1] Johnson M. Paediatr Respir Rev. 2006;7(Suppl 1):S3–S7.

[2] Liu Y, He Y, Wang K. Phytother Res. 2019;33(3):571–582.

[3] Cherezov V, Rosenbaum DM, Hanson MA, et al. Science. 2007;318(5854):1258–1265.

[4] Kim YJ, et al. J Mol Graph Model. 2017;76:1-9.

[5] Wang L, et al. Biomed Pharmacother. 2021;134:111066.