Molecular Surface Analysis: A Computer Assisted Search for Structure-Odor Relationship

The techniques used in isolation and identification of the components of flavor and fragrance materials have so improved over the years that we can produce almost any desired reconstituted facsimile, often of excellent quality. And yet we know very little about what is going on at the molecular level, of how molecules interact with olfactory receptors, or what governs the specificity and intensity of the response.

If we were to gain greater understanding of the basic mechanism of olfaction it would be a tremendous aid in our efforts to develop new and improved flavors and fragrances. There are two main reasons why this is so. First, we would then be able to quantitatively correlate olfactory response with physiochemical parameters, i.e., we could predict the type of odor or flavor and its strength from measurable data. This would allow mathematical description of olfactory nuances and permit optimization of recipes. Secondly, we would then be able to design new molecules with predicted organoleptic properties. Such a rational approach would likely result in a higher success rate in the synthesis of new and useful flavors and fragrances. Consider that at present the usual operation is guided by the philosophy “let’s make and evaluate every synthetic analog we can think of.”

The most prevalent olfactory theory invokes the “key in lock” model of reception. A receptor site is stimulated when it can be effectively occupied by a molecule. Stimulation would then correlate with those parameters relating to the ability of the molecule to be transported to the receptor site, to its chemical affinity for the site, and to its physical dimensions, or shape, which would regulate its ability to enter the site. Since physiological experiments have been unable to show high specificity of respnse in olfactory receptors, the interaction mechanism is probably more complex, perhaps involving the fit of a molecule into several different receptors.

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