Invited
The taste of molecules: A bitter-sweet tale

Taste has a key impact on food acceptance and consumption, with a handful of basic taste modalities (bitter, sweet, umami, salty, sour) eliciting innate attractive or aversive reactions.

Aversive bitter taste is traditionally assumed to guard against toxicity, while attractive sweet taste is a sensor for carbohydrates. However, some bitter molecules are not toxic, and calorie-free compounds can elicit sweet taste.

We have recently expanded the free electronic resource of bitter ligands, the BitterDB¹, which holds information for over 1000 bitter molecules. Furthermore, we developed a machine learning classifier, BitterPredict², that predicts whether a molecule is bitter or not, based on its chemical structure only. Application of BitterPredict to large datasets of toxic and of pharmaceutical compounds showed that toxicity and bitterness are not as closely related as commonly assumed³, and highlighted the connection between bitterness and therapeutic potential. Finally, structure-based and ligand-based approaches, commonly used in drug discovery⁴ , will be highlighted as novel and useful tools towards rational design of tastants and taste-modifying compounds.

[1] Dagan-Wiener, A., Di Pizio, A., Nissim, I., Bahia, M. S., Dubovski, N., Margulis, E., and Niv, M. Y. (2018) BitterDB: taste ligands and receptors database in 2019, Nucleic acids research.

[2] Dagan-Wiener, A., Nissim, I., Ben Abu, N., Borgonovo, G., Bassoli, A., and Niv, M. Y. (2017) Bitter or not? BitterPredict, a tool for predicting taste from chemical structure, Sci Rep 7, 12074.

[3] Nissim, I., Dagan-Wiener, A., and Niv, M. Y. (2017) The taste of toxicity: A quantitative analysis of bitter and toxic molecules, IUBMB Life 69, 938-946.

[4] Bahia, M. S., Nissim, I., and Niv, M. Y. (2018) Bitterness prediction in-silico: A step towards better drugs, Int J Pharm 536, 526-529.