# Decoding the Molecular Mechanisms of Menthol Isomer Perception Based on Computational Simulations

## TL;DR

This study explores how different menthol isomers are perceived through smell and identifies molecular interactions that explain their distinct odors.

## Contribution

The study reveals the molecular mechanisms behind the perception of menthol isomers using sensory analysis and computational simulations.

## Key findings

- L-menthol has a pleasant mint-like odor with no off-flavors, while other isomers have negative aromas.
- Hydrogen bonding and hydrophobic interactions are key in the binding of menthol isomers to olfactory receptors.
- Specific amino acid residues in receptors contribute significantly to the recognition of menthol isomers.

## Abstract

The flavor characteristics, perception, and molecular mechanisms of eight menthol isomers were investigated by sensory analysis combined with computational simulations. The sensory analysis results show significant differences in the odor profiles of the different menthol isomers. Among them, L-menthol shows a pleasant, sweet, and mint-like odor with a distinct freshness and no off-flavors, whereas the remaining seven isomers were interspersed with negative odors (musty, herbal, or earthy aromas). L-menthol and D-menthol had the lowest detection thresholds of 5.166 and 4.734 mg/L, respectively. The molecular docking results of the menthol isomers with olfactory receptors (Olfr874, OR8B8, and OR8B12) indicate that hydrogen bonding and hydrophobic interactions were the key binding forces. The binding energy ranged from −7.3 to −5.1 kcal/mol. Residues His-55 (Olfr874), Thr-56 (Olfr874), Leu-55 (OR8B8), Tyr-94 (OR8B8), Thr-57 (OR8B8), Phe-199 (OR8B12), and Ser-248 (OR8B12) with high frequencies particularly contributed to the recognition of menthol isomers. These findings contribute to a deeper understanding of the olfactory perception mechanism of menthol and provide data support for the development and precise application of minty odorants.