The taste of molecules: on bitterness, match-making and drugs
Masha Niv, The Institute of Biochemistry, Food Science and Nutrition and The Fritz Haber Center, The Hebrew University of Jerusalem
Taste is a major driver of food choice and consumption. Bitter (caffeine, quinine, strychnine and many more), sweet (sugars, sweet proteins, artificial sweeteners) and umami (glutamate, often consumed as MSG) molecules are recognized by taste receptors that belong to the GPCR family.
There are 25 subtypes of bitter taste receptors, which recognize over 1000 chemically diverse ligands . While some TAS2Rs are broadly tuned with more than 100 agonists, others are very selective with very few known ligands .
I will present a Netflix-inspired approach for matching ligands to their bitter taste receptors. The algorithm uses chemical and structural features of the ligands and the receptors. In addition, it uses known ligand-receptor (“customer-product”) associations and collaborative similarity features, similarly to recommendation systems used in e-commerce applications.
BitterMatch allows reduction of the number of in-vitro tests required for finding the cognate receptors. Testing of prospective predictions shows precision of ~80% and recall of ~50%. For some bitter taste receptors precision and recall are over 90% and 70%.
For one such receptor, T2R14, we design improved ligands by iteratively combining structure-based modeling with experiment , with potential implications for drug discovery .
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