Neuroreceptor Activation by Vibration-Assisted Tunneling
<p dir="ltr">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 under...
محفوظ في:
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| مؤلفون آخرون: | , , |
| منشور في: |
2015
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| _version_ | 1864513505663647744 |
|---|---|
| author | Ross D. Hoehn (1836382) |
| author2 | David Nichols (3527624) Hartmut Neven (19651873) Sabre Kais (1409968) |
| author2_role | author author author |
| author_facet | Ross D. Hoehn (1836382) David Nichols (3527624) Hartmut Neven (19651873) Sabre Kais (1409968) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ross D. Hoehn (1836382) David Nichols (3527624) Hartmut Neven (19651873) Sabre Kais (1409968) |
| dc.date.none.fl_str_mv | 2015-04-24T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/srep09990 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Neuroreceptor_Activation_by_Vibration-Assisted_Tunneling/27001933 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Medical biochemistry and metabolomics Medical physiology Neurosciences Pharmacology and pharmaceutical sciences Information and computing sciences Theory of computation Biophysical chemistry Mechanism of action Drug design Serotonin receptor Deuterated isotopologues Neurobiology Quantum chemical modeling |
| dc.title.none.fl_str_mv | Neuroreceptor Activation by Vibration-Assisted Tunneling |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/srep09990" target="_blank">https://dx.doi.org/10.1038/srep09990</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_d846c3126eacb3b149e58959b63d2d42 |
| identifier_str_mv | 10.1038/srep09990 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/27001933 |
| publishDate | 2015 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Neuroreceptor Activation by Vibration-Assisted TunnelingRoss D. Hoehn (1836382)David Nichols (3527624)Hartmut Neven (19651873)Sabre Kais (1409968)Biomedical and clinical sciencesMedical biochemistry and metabolomicsMedical physiologyNeurosciencesPharmacology and pharmaceutical sciencesInformation and computing sciencesTheory of computationBiophysical chemistryMechanism of actionDrug designSerotonin receptorDeuterated isotopologuesNeurobiologyQuantum chemical modeling<p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Scientific Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/srep09990" target="_blank">https://dx.doi.org/10.1038/srep09990</a></p>2015-04-24T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/srep09990https://figshare.com/articles/journal_contribution/Neuroreceptor_Activation_by_Vibration-Assisted_Tunneling/27001933CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/270019332015-04-24T06:00:00Z |
| spellingShingle | Neuroreceptor Activation by Vibration-Assisted Tunneling Ross D. Hoehn (1836382) Biomedical and clinical sciences Medical biochemistry and metabolomics Medical physiology Neurosciences Pharmacology and pharmaceutical sciences Information and computing sciences Theory of computation Biophysical chemistry Mechanism of action Drug design Serotonin receptor Deuterated isotopologues Neurobiology Quantum chemical modeling |
| status_str | publishedVersion |
| title | Neuroreceptor Activation by Vibration-Assisted Tunneling |
| title_full | Neuroreceptor Activation by Vibration-Assisted Tunneling |
| title_fullStr | Neuroreceptor Activation by Vibration-Assisted Tunneling |
| title_full_unstemmed | Neuroreceptor Activation by Vibration-Assisted Tunneling |
| title_short | Neuroreceptor Activation by Vibration-Assisted Tunneling |
| title_sort | Neuroreceptor Activation by Vibration-Assisted Tunneling |
| topic | Biomedical and clinical sciences Medical biochemistry and metabolomics Medical physiology Neurosciences Pharmacology and pharmaceutical sciences Information and computing sciences Theory of computation Biophysical chemistry Mechanism of action Drug design Serotonin receptor Deuterated isotopologues Neurobiology Quantum chemical modeling |