Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations.
Sci Rep
; 8(1): 13787, 2018 09 13.
Article
em En
| MEDLINE
| ID: mdl-30213978
ABSTRACT
Cannabinoid receptor 1 (CB1) is a promising therapeutic target for a variety of disorders. Distinct efficacy profiles showed different therapeutic effects on CB1 dependent on three classes of ligands agonists, antagonists, and inverse agonists. To discriminate the distinct efficacy profiles of the ligands, we carried out molecular dynamics (MD) simulations to identify the dynamic behaviors of inactive and active conformations of CB1 structures with the ligands. In addition, the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method was applied to analyze the binding free energy decompositions of the CB1-ligand complexes. With these two methods, we found the possibility that the three classes of ligands can be discriminated. Our findings shed light on the understanding of different efficacy profiles of ligands by analyzing the structural behaviors of intact CB1 structures and the binding energies of ligands, thereby yielding insights that are useful for the design of new potent CB1 drugs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dronabinol
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Canabinoides
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Desenho de Fármacos
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Receptor CB1 de Canabinoide
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Agonistas de Receptores de Canabinoides
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Antagonistas de Receptores de Canabinoides
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article