Structure-threshold relationship in food aroma molecules: Insights from S-curve method, molecular docking, and dynamics simulations

This study investigates structure-odor threshold relationships of aroma compounds using integrated S-curve analysis, molecular docking, and dynamics simulations. Molecular docking revealed odor thresholds were independent of binding energies but sensitive to structural variations, which altered receptor interaction pattern: eugenol formed hydrogen bonds with SER183, while its isomer isoeugenol preferentially bound TYR260. Similarly, phenylethyl alcohol established TYR278 hydrogen bonding absent in phenylethyl aldehyde. Molecular dynamics simulations identified hydrogen bond stability and receptor conformational flexibility as threshold determinants, exhibiting more stable hydrogen bonds and greater conformational flexibility displayed lower detection thresholds. These findings establish a predictive framework linking molecular structural features to odor thresholds while elucidating ligand-receptor interaction mechanisms, providing theoretical foundations for rational flavor design and sensory modulation strategies.