PREDICTING THE TASTE OF MOLECULES

Bitter taste is essential for survival, as it protects against consuming poisonous compounds, which are often bitter. Bitter taste perception can be elicited by numerous chemically dissimilar compounds(Wiener, et al., 2012) and is mediated by bitter taste receptors (TAS2Rs), a subfamily of GPCRs(Di Pizio and Niv, 2014). Some TAS2Rs are still orphan, while others can be activated by numerous, structurally dissimilar compounds(Levit, et al., 2014).

We use ligand-based, structure-based and machine learning approaches to identify bitter compounds based on structure, compatibility to receptor, and molecular properties of the candidate molecules(Levit, et al., 2014). Some bitter compounds are selective towards a single TAS2R, while others activate multiple TAS2Rs. Interestingly, selective TAS2Rs are typically activated by promiscuous compounds, which are already recognized by additional TAS2Rs. Thus, if unique ligands have been the evolutionary driving force for the development of selective TAS2Rs, they still need to be unraveled(Di Pizio and Niv, 2015). This is of particular interest not only because of the role of taste receptors in regulating food consumption, but also due to the recently discovered expression of taste receptors in various extra-oral tissues, and the emerging role of TAS2Rs as novel therapeutic targets.

Di Pizio, A. and Niv, M.Y. Promiscuity and selectivity of bitter molecules and their receptors. Bioorganic & medicinal chemistry 2015;23(14):4082-4091.

Di Pizio, A. and Niv, M.Y. Computational Studies of Smell and Taste Receptors. Israel Journal of Chemistry 2014;54(8-9):1205-1218.

Levit, A., et al. The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14. FASEB journal 2014;28(3):1181-1197.

Wiener, A., et al. BitterDB: a database of bitter compounds. Nucleic Acids Res 2012;40(Database issue):D413-419.