Neuroreceptor Activation by Vibration-Assisted Tunneling
Ross D Hoehn, David Nichols, Hartmut Neven, Sabre Kais
A theoretical model suggests a molecule's vibration, not just its shape, may determine how it activates a neural receptor.
G protein-coupled receptors (GPCRs) constitute a large family of receptor proteinsthat sense molecular signals on the exterior of a cell and activate signaltransduction pathways within the cell. Modeling how an agonist activates such areceptor is fundamental for an understanding of a wide variety of physiologicalprocesses and it is of tremendous value for pharmacology and drug design. Inelasticelectron tunneling spectroscopy (IETS) has been proposed as a model for themechanism by which olfactory GPCRs are activated by a bound agonist. We apply thishyothesis to GPCRs within the mammalian nervous system using quantum chemicalmodeling. We found that non-endogenous agonists of the serotonin receptor share aparticular IET spectral aspect both amongst each other and with the serotoninmolecule: a peak whose intensity scales with the known agonist potencies. We proposean experiential validation of this model by utilizing lysergic acid dimethylamide(DAM-57), an ergot derivative and its deuterated isotopologues; we also providetheoretical predictions for comparison to experiment. If validated our theory mayprovide new avenues for guided drug design and elevate methods of in silicopotency/activity prediction.
Fascia as a flow is a new way of understanding the body and explaining the body’s function. All that lives has a flow. Each living cell or organism has a flow of water, energies,…
The episode was first published on the Swedish podcast Fasciaguiden on June 5, 2025. In this thought-provoking conversation, we meet Dr. Neil Theise — liver pathologist, fascia re…