Olfactory Perception and Receptor Binding of Damascone Isomers: Unravelling the Role of Double Bond Configuration

ABSTRACT The molecular architecture of odorants, nuanced by factors such as chirality and carbon chain length, significantly influences sensory perception. Despite this, the role of double bond isomerization in olfactory evaluation remains underexplored. This study delves into how the double‐bond rearrangement in damascone impacts flavour perception, combining sensory evaluation and computational simulation. Sensory results showed that α ‐ and δ ‐damascone had more pronounced minty notes, while β ‐and δ ‐damascone exhibited more significant floral ones. Notably, the odour thresholds determined via the S‐curve method were 0.0145 μg/mL, 0.0373 μg/mL and 0.0011 μg/mL for α ‐, β ‐ and δ ‐isomers, respectively, indicating a significant difference in potency. To further investigate the influence of double bond rearrangement on receptor binding, molecular docking and molecular dynamic simulations were utilised. Molecular docking revealed that δ ‐damascone had the lowest binding energy, correlating with its high potency, and identified key interactions with residues such as TYR‐262 and TYR‐251. Molecular dynamics simulations further demonstrated that double bond isomerization affected the binding stability between the three damascones and olfactory receptors, as evidenced by root‐mean‐square deviation (RMSD) fluctuations, with α ‐ and δ ‐damascone forming more stable complexes. Together, these results provide a mechanistic understanding of how double bond configuration dictates damascone odour perception through distinct receptor binding modes.