Identification of hTAS2R38 bitter taste receptor antagonists via homology modeling and molecular docking

Taste receptor type 2 members (TAS2Rs), a family of G protein-coupled receptors, comprise a single polypeptide chain with seven transmembrane helices, three extracellular loops, and three intracellular loops. These receptors detect structurally diverse bitter compounds, playing a vital role in taste perception. Among them, TAS2R38 is a key bitter taste receptor that modulates bitter taste perception and dietary preferences. In this study, we focused on human TAS2R38, utilizing homology modeling based on squid rhodopsin (PDB ID: 3AYN) to predict its 3D structure. Potential antagonists were screened via molecular docking, with calcium imaging identifying Compound 58 as a promising candidate. Further docking analysis revealed that its amino group is critical for receptor binding. Our findings demonstrate that homology modeling combined with structure-based screening effectively identifies hTAS2R38 antagonists, offering insights for advancing bitterness-masking strategies.