Molecular modelling and models in the study of sweet and umami taste receptors : A review

The mechanism of action of tastants has been under investigation for many years. For the sweet taste several models have been developed to describe the nature and topological arrangement of the glucophores of ideal sweet compounds and/or the recognition sites of the sweet taste receptor. In less than a decade our knowledge about the mechanism of sweet taste chemoreception has grown enormously, following the identification and cloning of T1Rs. The observation that receptor cells co-expressing T1R2 and T1R3 respond to a great variety of sweet compounds has been generally interpreted as an inference that there is a single heterodimeric receptor for sweet taste. The three-dimensional structure of the receptor is not known and alternative methodologies are required to model the binding of sweet compounds. Therefore homology modelling and molecular modelling become indispensable tools to suggest point mutations which further define the binding regions. Only their cooperative effect allowed researchers to determine several molecular mechanisms of the sweet taste receptors, including the modality of action of blockers and positive allosteric modulators. For umami taste, despite the general appreciation of the meaty, mouth filling and rich taste found in many foods (and the great interest of the food industry thereof), the existence of an umami receptor has been accepted only after its cloning. Probably because of this, no umami taste receptor models have been developed, while the molecular mechanism for its synergism has been unravelled before that of the sweet taste receptor.