Mostrar el registro sencillo del ítem
dc.contributor.author
Alvarez, Lautaro Damian
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Alves, Norma Roxana Carina
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.date.available
2023-08-29T18:03:09Z
dc.date.issued
2022-10
dc.identifier.citation
Alvarez, Lautaro Damian; Alves, Norma Roxana Carina; Molecular determinants of tetrahydrocannabinol binding to the glycine receptor; Wiley-liss, div John Wiley & Sons Inc.; Proteins: Structure, Function And Genetics; 91; 3; 10-2022; 400-411
dc.identifier.issn
0887-3585
dc.identifier.uri
http://hdl.handle.net/11336/209813
dc.description.abstract
The recognition of Cannabis as a source of new compounds suitable for medical use has attracted strong interest from the scientific community in its research, and substantial progress has accumulated regarding cannabinoids' activity; however, a thorough description of their molecular mechanisms of action remains a task to complete. Highlighting their complex pharmacology, the list of cannabinoids' interactors has vastly expanded beyond the canonical cannabinoid receptors. Among those, we have focused our study on the glycine receptor (GlyR), an ion channel involved in the modulation of nervous system responses, including, to our interest, sensitivity to peripheral pain. Here, we report the use of computational methods to investigate possible binding modes between the GlyR and Δ9-tetrahydrocannabinol (THC). After obtaining a first pose for the THC binding from a biased molecular docking simulation and subsequently evaluating it by molecular dynamic simulations, we found a dynamic system with an identifiable representative binding mode characterized by the specific interaction with two transmembrane residues (Phe293 and Ser296). Complementarily, we assessed the role of membrane cholesterol in this interaction and positively established its relevance for THC binding to GlyR. Lastly, the use of restrained molecular dynamics simulations allowed us to refine the description of the binding mode and of the cholesterol effect. Altogether, our findings contribute to the current knowledge about the GlyR-THC mode of binding and propose a new starting point for future research on how cannabinoids in general, and THC in particular, modulate pain perception in view of its possible clinical applications.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley-liss, div John Wiley & Sons Inc.
![Confianza no establecida para este valor](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
BINDING MODE
dc.subject
CANNABINOIDS
dc.subject
DOCKING
dc.subject
GLYCINE RECEPTORS
dc.subject
MOLECULAR DYNAMICS SIMULATION
dc.subject
∆9-TETRAHYDROCANNABINOL
dc.subject.classification
Otras Ciencias Químicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
Ciencias Químicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.title
Molecular determinants of tetrahydrocannabinol binding to the glycine receptor
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-06-30T10:46:29Z
dc.identifier.eissn
1097-0134
dc.journal.volume
91
dc.journal.number
3
dc.journal.pagination
400-411
dc.journal.pais
Estados Unidos
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.journal.ciudad
Nueva York
dc.description.fil
Fil: Alvarez, Lautaro Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
dc.description.fil
Fil: Alves, Norma Roxana Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
dc.journal.title
Proteins: Structure, Function And Genetics
![Confianza no establecida para este valor](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/prot.26438
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1002/prot.26438
Archivos asociados