Ligand recognition mechanism and structure-activity relationship of TAS2R1 revealed by a CMK-3/AuNPs sensor and computational modeling

Developed an electrochemical biosensor for the bitter taste receptor TAS2R1, utilizing a nanocomposite of CMK-3 and AuNPs. • Proposed system-dependent C₁/₂,sys to quantify ligand-triggered electrochemical signals of the TAS2R1 biosensor. • H-bond & hydrophobic forces govern TAS2R1-ligand binding; Phe75, Ile254, Leu250, Phe252/259, Arg256 are key binding residues. The bitter taste receptor TAS2R1 mediates significant physiological functions not only in the gustatory system but also in extra-oral tissues, including the respiratory tract, immune system, and metabolic pathways. To elucidate its ligand recognition mechanism, we developed an electrochemical biosensor for TAS2R1 based on a composite of ordered mesoporous carbon and gold nanoparticles. The biosensor was used to quantitatively analyze the interaction kinetics with ten bitter ligands. Combined with molecular docking and molecular dynamics simulations, this study identified key residues in TAS2R1 that may be involved in ligand recognition; among these, the nitrogen-containing groups and hydroxyl groups of the ligand molecules appear to be important structural features influencing ligand recognition by TAS2R1. This work provides a molecular foundation for elucidating the structure-activity relationship of TAS2R1 and facilitates its applications in bitter taste masking and drug development. Download: Download high-res image (174KB) Download: Download full-size image