Modelling of ORL1 receptor-ligand interactions
Apstrakt
An opioid receptor like (ORL1) receptor is one of a family of G-protein-coupled receptors (GPCR); it represents a new pharmaceutical target with extensive therapeutic potential for the regulation of important biological functions such as nociception, mood disorders, drug abuse, learning or cardiovascular control. Although the crystal structure of the inactive form of the ORL1 receptor has been determined, little is known about its activation. By using X-ray structures of the beta 2-adrenegic receptor in its inactive (2RH1) and active (3P0G) states as templates, inactive and active homology models of the ORL1 receptor were constructed. Structurally diverse sets of strongly binding antagonists and agonists were docked with both ORL1 receptor forms. The major receptor-ligand interactions responsible for antagonist and agonist binding were identified. Although both sets of ligands, agonists and antagonists, bind to the same region of the receptor, they occupy partially different binding po...ckets. Agonists bind to the inactive receptor in a slightly different manner than antagonists. This difference is more pronounced in binding to the active ORL1 receptor model and points to the amino acids at the extracellular end of TM6, suggesting that this region is important for receptor-activation. (C) 2014 Institute of Chemistry, Slovak Academy of Sciences
Ključne reči:
molecular modelling / ORL1 receptor / ligand-receptor interactions / docking simulation / molecular dynamicsIzvor:
CHEMICAL PAPERS, 2014, 68, 10, 1305-1316Izdavač:
- Springer International Publishing Ag, Cham
Finansiranje / projekti:
- Proučavanje odnosa strukture i aktivnosti novosintetisanih biološki aktivnih supstanci (RS-MESTD-Basic Research (BR or ON)-172032)
- Racionalni dizajn i sinteza biološki aktivnih i koordinacionih jedinjenja i funkcionalnih materijala, relevantnih u (bio)nanotehnologiji (RS-MESTD-Basic Research (BR or ON)-172035)
DOI: 10.2478/s11696-014-0577-z
ISSN: 2585-7290
WoS: 000338283600003
Scopus: 2-s2.0-84903700431
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Senćanski, Milan AU - Ivanović, Milovan AU - Došen-Mićović, Ljiljana PY - 2014 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1801 AB - An opioid receptor like (ORL1) receptor is one of a family of G-protein-coupled receptors (GPCR); it represents a new pharmaceutical target with extensive therapeutic potential for the regulation of important biological functions such as nociception, mood disorders, drug abuse, learning or cardiovascular control. Although the crystal structure of the inactive form of the ORL1 receptor has been determined, little is known about its activation. By using X-ray structures of the beta 2-adrenegic receptor in its inactive (2RH1) and active (3P0G) states as templates, inactive and active homology models of the ORL1 receptor were constructed. Structurally diverse sets of strongly binding antagonists and agonists were docked with both ORL1 receptor forms. The major receptor-ligand interactions responsible for antagonist and agonist binding were identified. Although both sets of ligands, agonists and antagonists, bind to the same region of the receptor, they occupy partially different binding pockets. Agonists bind to the inactive receptor in a slightly different manner than antagonists. This difference is more pronounced in binding to the active ORL1 receptor model and points to the amino acids at the extracellular end of TM6, suggesting that this region is important for receptor-activation. (C) 2014 Institute of Chemistry, Slovak Academy of Sciences PB - Springer International Publishing Ag, Cham T2 - CHEMICAL PAPERS T1 - Modelling of ORL1 receptor-ligand interactions VL - 68 IS - 10 SP - 1305 EP - 1316 DO - 10.2478/s11696-014-0577-z ER -
@article{ author = "Senćanski, Milan and Ivanović, Milovan and Došen-Mićović, Ljiljana", year = "2014", abstract = "An opioid receptor like (ORL1) receptor is one of a family of G-protein-coupled receptors (GPCR); it represents a new pharmaceutical target with extensive therapeutic potential for the regulation of important biological functions such as nociception, mood disorders, drug abuse, learning or cardiovascular control. Although the crystal structure of the inactive form of the ORL1 receptor has been determined, little is known about its activation. By using X-ray structures of the beta 2-adrenegic receptor in its inactive (2RH1) and active (3P0G) states as templates, inactive and active homology models of the ORL1 receptor were constructed. Structurally diverse sets of strongly binding antagonists and agonists were docked with both ORL1 receptor forms. The major receptor-ligand interactions responsible for antagonist and agonist binding were identified. Although both sets of ligands, agonists and antagonists, bind to the same region of the receptor, they occupy partially different binding pockets. Agonists bind to the inactive receptor in a slightly different manner than antagonists. This difference is more pronounced in binding to the active ORL1 receptor model and points to the amino acids at the extracellular end of TM6, suggesting that this region is important for receptor-activation. (C) 2014 Institute of Chemistry, Slovak Academy of Sciences", publisher = "Springer International Publishing Ag, Cham", journal = "CHEMICAL PAPERS", title = "Modelling of ORL1 receptor-ligand interactions", volume = "68", number = "10", pages = "1305-1316", doi = "10.2478/s11696-014-0577-z" }
Senćanski, M., Ivanović, M.,& Došen-Mićović, L.. (2014). Modelling of ORL1 receptor-ligand interactions. in CHEMICAL PAPERS Springer International Publishing Ag, Cham., 68(10), 1305-1316. https://doi.org/10.2478/s11696-014-0577-z
Senćanski M, Ivanović M, Došen-Mićović L. Modelling of ORL1 receptor-ligand interactions. in CHEMICAL PAPERS. 2014;68(10):1305-1316. doi:10.2478/s11696-014-0577-z .
Senćanski, Milan, Ivanović, Milovan, Došen-Mićović, Ljiljana, "Modelling of ORL1 receptor-ligand interactions" in CHEMICAL PAPERS, 68, no. 10 (2014):1305-1316, https://doi.org/10.2478/s11696-014-0577-z . .