Sweet Taste and Chirality – Interactions of Sugars with the Human Sweet Taste Receptor

Sweet taste is one of the primary determinants of food preference and intake and has a huge impact on health and global economy, leading to constant search for cost effective, healthy, novel sweeteners. Here we analyze the molecular recognition of ligands by the sweet taste receptor, focusing on the role of chirality in the sweetness of sugars and amino acids. The sweet taste receptor is comprised of Tas1R2 and Tas1R3 monomers. Homology modeling of the extracellular Venus Fly Trap (VFT) domain of the receptors was based on the metabotropic glutamate receptors (mGluR) Xray structures. Next, an automated docking campaign to screen the models against their known ligands (and decoys with similar physicochemical properties but dissimilar 2D topologies) was carried out. After establishment of a good computational model to work with, we analyzed the interactive residues in the binding site. The predicted interactions are unique as sugar-binding, stereospecific and enhancer-binding residues. Our results successfully predicted the interacting residues of the sweet taste VFT domain. We also suggest newly identified interacting-residues with specific information about the role of the residues in the activation of the sweet taste receptor.