Computational modeling study of functional microdomains in cannabinoid receptor type 1

Angel Gonzalez, Leonardo Sepulveda Duran, Raul Araya-Secchi, Jose A. Garate, C. David Pessoa-Mahana, Carlos F. Lagos, Tomas Perez-Acle

Resultado de la investigación: Contribución a una revistaArtículo

23 Citas (Scopus)

Resumen

The seven transmembrane helices (TMH) G-protein-coupled receptors (GPCRs) constitute one of the largest superfamily of signaling proteins found in mammals. Some of its members, in which the cannabinoid (CB) receptors are included, stand out because their functional states can be modulated by a broad spectrum of effector molecules. The relative ligand promiscuity exhibited by these receptors could be related with particular attributes conferred by their molecular architecture and represents a motivating issue to be explored. In this regard, this study represents an effort to investigate the cannabinoid receptor type 1 (CB1) ligand recognition plasticity, using comparative modeling, molecular dynamics (MD) simulations and docking. Our results suggest that a cooperative set of subtle structural rearrangements within the TMHs provide to the CB1 protein the plasticity to reach alternate configurations. These changes include the relaxation of intramolecular constraints, the rotations, translations and kinks of the majority of TMHs and the reorganization of the ligand binding cavities.

Idioma originalInglés
Páginas (desde-hasta)4378-4389
Número de páginas12
PublicaciónBioorganic and Medicinal Chemistry
Volumen16
N.º8
DOI
EstadoPublicada - 15 abr 2008

Áreas temáticas de ASJC Scopus

  • Bioquímica
  • Medicina molecular
  • Biología molecular
  • Ciencias farmacéuticas
  • Descubrimiento de medicamentos
  • Bioquímica clínica
  • Química orgánica

Huella Profundice en los temas de investigación de 'Computational modeling study of functional microdomains in cannabinoid receptor type 1'. En conjunto forman una huella única.

  • Citar esto

    Gonzalez, A., Duran, L. S., Araya-Secchi, R., Garate, J. A., Pessoa-Mahana, C. D., Lagos, C. F., & Perez-Acle, T. (2008). Computational modeling study of functional microdomains in cannabinoid receptor type 1. Bioorganic and Medicinal Chemistry, 16(8), 4378-4389. https://doi.org/10.1016/j.bmc.2008.02.070