Sweetness enhancement through aroma has been suggested as a strategy to mitigate sugar addition in foods, but such enhancement depends on the type of aroma. Ethyl propanoate, ethyl 2-methylbutanoate, octyl acetate, ethyl butanoate, ethyl hexanoate, butyl hexanoate, γ-terpinene, nootkatone, and acetophenone with fruity aroma from sweet orange were selected as the objects to investigate the sweetening effect of aroma compounds in a 5% sucrose solution using an artificial sensory tongue and an electronic tongue. The results showed that nine aroma compounds exerted a significant effect on the sweetness, among which ethyl butanoate, ethyl propanoate, and ethyl 2-methylbutanoate imparted a more comfortable effect. Subsequently, the mechanism of their sweetening action was studied by molecular simulation. Molecular docking results indicated that the binding free energy decreased below −5.9 kcal/mol in the presence of aroma compounds, indicating that sucrose was more tightly docked to the sweet taste receptor. Molecular dynamics (MD) further implied that under the influence of ethyl butanoate, the stable time of binding was advanced by 15 ns, and the amino acids forming hydrogen bonds changed from LYS65, ASP278, GLU302, SER165, and SER303 to SER165, ASP142, LYS65, and GLU302. The interaction depends on hydrogen bonds, water bridges, and hydrophobic forces.
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