Ultimate Molecular Theory of Bitter Taste

More than thirty years ago, I proposed a theory about sweet and bitter molecules’ recognition by protein helical structures. Unfortunately the papers could not go to public platform until now. Inspired by the sweet taste theory^1,2, this bitter taste theory conveys that bitter molecules are recognized by receptor protein helical structures. The recognition process is a dynamic action, in which the receptor protein helices have a torsion-spring-like oscillation between helical structures of 3.6 and 4 amino acids per turn. Based on the characteristics of the bitter receptor protein helix oscillation, it perfectly explains why in bitter molecules, only one unit of hydrogen donor (DH) or hydrogen acceptor (B) is enough in helping molecules to elicit bitter taste. The potential DH and B in bitter receptor are any NH or O of receptor’s peptide NHs and Os, which are the ones forming intramolecular H-bonds responsible for the formation of receptor protein helical structures. Furthermore, only one unit of DH or B is allowed for structurally simple ligands. As recognition sites are only associated with a small fraction – helix structure of whole bitter receptor, multiple binding sites or multiple receptors are well expected. As the oscillation may have different extent, it translates to bitterness intensity. According to ligand-receptor binding motion, bitter receptor could be divided into two kinds of spaces, which are similar to the situation in sweet taste receptor: main and side grooves. These have been discussed in context and especially great details in paper titled deciphering aspartyl peptide sweeteners ².