Experimental evaluation of the generalized vibrational theory of G protein-coupled receptor activation

Ross Hoehn, David E. Nichols, John D. McCorvy, Hartmut Neven, Sabre Kais

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5 Citations (Scopus)

Abstract

Recently, an alternative theory concerning the method by which olfactory proteins are activated has garnered attention. This theory proposes that the activation of olfactory G protein-coupled receptors occurs by an inelastic electron tunneling mechanism that is mediated through the presence of an agonist with an appropriate vibrational state to accept the inelastic portion of the tunneling electron's energy. In a recent series of papers, some suggestive theoretical evidence has been offered that this theory may be applied to nonolfactory G protein-coupled receptors (GPCRs), including those associated with the central nervous system (CNS). [Chee HK, June OS (2013) Genomics Inform 11(4):282-288; Chee HK, et al. (2015) FEBS Lett 589(4):548-552; Oh SJ (2012) Genomics Inform 10(2):128-132]. Herein, we test the viability of this idea, both by receptor affinity and receptor activation measured by calcium flux. This test was performed using a pair of well-characterized agonists for members of the 5-HT2 class of serotonin receptors, 2,5-dimethoxy-4-iodoamphetamine (DOI) and N,N-dimethyllysergamide (DAM-57), and their respective deuterated isotopologues. No evidence was found that selective deuteration affected either the binding affinity or the activation by the selected ligands for the examined members of the 5-HT2 receptor class.

Original languageEnglish
Pages (from-to)5595-5600
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number22
DOIs
Publication statusPublished - 30 May 2017
Externally publishedYes

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Keywords

  • Electron tunneling
  • Mechanism of action
  • Pharmacology
  • Protein
  • Quantum biology

ASJC Scopus subject areas

  • General

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