Computational studies of smell and taste receptors

Antonella Di Pizio, Masha Y. Niv

Research output: Contribution to journalReview articlepeer-review

Abstract

Smell and taste are among the basic senses with which we perceive the world around us. In addition to enabling recognition of chemical moieties that provide social or nutritional clues, taste and smell receptors are expressed in many extraoral tissues, including the gastrointestinal, respiratory, and reproductive systems. It is, therefore, likely that taste and smell receptors have additional physiological roles, which are currently under intensive study. Most of the taste modalities, as well as olfaction, are mediated by G-protein coupled receptors (GPCRs). Recent breakthroughs in crystallography and signaling studies of GPCRs (celebrated by the 2012 Nobel Prize in Chemistry to Robert Lefkowitz and Brian Kobilkprovide excellent opportunities for applying this information towards furthering our understanding of taste and smell signaling. No crystal structures of odorant or taste receptors are currently available. However, computational techniques, many of which stem from the pioneering contributions of the 2013 Nobel Prize in Chemistry laureates, Martin Karplus, Michael Levitt, and Arieh Warshel, can shed light on the function of taste and olfactory GPCRs. In this review, we highlight examples of iterative combinations of simulation and experiment that were successfully applied toward delineating binding modes of tastants and odorants and toward predicting additional ligands. Further studies are required in order to answer remaining questions regarding receptor promiscuity versus selectivity, the details of receptor coupling to G-proteins, and the roles of oligomerization and of allosteric modulation in taste and smell transduction.

Original languageAmerican English
Pages (from-to)1205-1218
Number of pages14
JournalIsrael Journal of Chemistry
Volume54
Issue number8-9
DOIs
StatePublished - 2014

Keywords

  • Odorant
  • Proteins
  • Receptors
  • Tastant
  • Theoretical chem

All Science Journal Classification (ASJC) codes

  • General Chemistry

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