Soft agonist receptor interactions: Theoretical and experimental simulation of the active site of the receptor of sweet molecules

The structure‐activity relationship of sweet molecules is chosen as an example to illustrate a mechanistic approach of soft agonist‐receptor interactions. It is shown that an essentially geometric model of the receptor site can explain the activity of most sweet molecules, both rigid and flexible. The relevant conformations of flexible molecules in solution are extracted from a combination of NMR data and of energy calculations. A possible experimental simulation of the receptor environment in solution is illustrated by the complex of a dipeptide sweetener with a crown‐ether.