Structure-based virtual screening of bitter taste receptors

Abstract

International audienceUnderstanding how chemicals code for a certain type of taste is fundamental for the development of a rational method to create new taste modulators. The identification of these new candidates is important for the food industry and would also be beneficial for the pharmacology industry. In humans, the bitter taste depends on a large family of 25 taste receptors type 2 (TAS2Rs) belonging to the G protein-coupled receptor (GPCR) family. They are classified distantly related to class A GPCR and, to date, the experimental structures have not been determined for any TAS2Rs. Here we present a new structure-based virtual screening strategy to expand the chemical space of bitter taste receptors. Combining molecular modeling (based on a recent general approach for modeling all mammal TAS2Rs1) and in vitro functional assays, we identified new active compounds as activators of human TAS2R10. Such agonists will be of broad interest beyond food science since TAS2Rs are ectopically expressed in other parts of the human body besides the tongue