We have shown computationally that the difference between the high-frequency C -H and C -D modes of propionate substantially exceeds the fluctuations due to the olfactory receptor environment at 310 K. It is not known with certainty whether OR51E2 can distinguish between hydrogenated and deuterated propionate, although a null result for C 2 H 3 D 2 COOH was reported by . If they can be distinguished by vibration, however, we predict that the mechanism involves only the high-frequency modes. This idea is in harmony with the way propionate binds to OR51E2 in the experimental structure: the C -H and C -D stretches, localized on the alkane tail of the olfactant, are close enough to interact with the F155 and L158 residues of OR51E2 . It may be that strong noncovalent interactions with the carboxylate group lead to recognition of propionate in general, while weaker couplings to the alkyl vibrational modes allow distinguishing of isotopic composition. For a more complete understanding of olfactant recognition, both electronic and vibrational interactions should be modeled; for isotopic differentiation, our work suggests that simulating highfrequency modes be prioritized.