Prediction of Bitter Taste Receptor’s Active Site

Non-steroidal anti-inflammatory drugs (NSAIDs) are considered as the best treatment for conditions
associated with pain, fever and inflammation. Non-steroidal anti-inflammatory drugs exert their
therapeutic effects by blocking prostaglandin synthesis from arachidonic acid, which inhibits the
activity of cyclooxygenases (COX-1 and COX-2). COX-1 is located in the stomach, kidney and other
tissues, while COX-2 is located at inflammation sites. One of the disadvantages of the NSAIDs is their
bitter sensation. This chapter discusses a novel approach to be used in the design of active sites of
bitter taste receptors, especially TAS2R14, by using the X-ray crystal structure of the enzyme COX-2
and chemical structures of commonly used non-steroidal anti-inflammatory drugs (NSAIDs) that bind
effectively to COX enzymes and activate the bitter taste receptor TAS2R14. The suggested approach
consists of docking calculations of the NSAIDs (ligands) to the active site of COX-2 and utilizing the
data obtained in better understanding the nature of the interactions between bitter tastants and the
chemical groups within the active site of TAS2R14 receptor.