Meaty Aroma Compounds Enhance MSG Umami Perception Through Allosteric Modulation of T1R1/T1R3 Receptor: Evidence from Nasal Clip Sensory Evaluation and Molecular Dynamics Simulation

Abstract

Background: Understanding how aroma compounds enhance monosodium glutamate (MSG) umami perception remains a critical challenge in flavor science. Methods: The umami-enhancing effects of meaty flavorings were investigated using nasal clip sensory evaluation (orthonasal blockage). Active aroma compounds were subsequently identified using gas chromatography-mass spectrometry (GC-MS). The three-dimensional structure of the umami receptor T1R1/T1R3 was constructed by homology modeling. The interaction mechanism was deciphered using molecular dynamics (MD) simulations. Results: Seafood essence S demonstrated the most potent umami enhancement. Five key compounds significantly intensified the MSG umami intensity: methional, dimethyl sulfide (DMS), D-limonene (DLE), 2,3-dimethylpyrazine, and dimethyl trisulfide. Notably, this enhancement persisted even under nasal clip conditions, revealing a novel mechanism independent of cross-modal interactions. Sulfur-containing compounds consistently demonstrated umami-enhancing effects across the evaluation conditions. MD simulations showed that aroma compounds induced allosteric remodeling of T1R1/T1R3, strengthening MSG-receptor hydrogen bonding (1.8–2.6-fold increase), reducing receptor flexibility, and stabilizing the ternary complex. Binding affinity was highest for DMS, followed by DLE and methional. Conclusion: This study provides the first receptor-level evidence that aroma compounds directly modulate MSG-taste receptor interactions through allosteric regulation, offering a novel theoretical framework for odor–taste interactions with significant implications for umami enhancer design and flavor research.