Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations

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 profile...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sang Won Jung, Art E. Cho, Wookyung Yu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Cannabinoid Receptor (CB1) Ligand Efficacy Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) Binding Free Energy Active Conformation Medicine R Science Q
Acceso en línea:	https://doaj.org/article/29d497457f834dadb0833af41d4d3654
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:29d497457f834dadb0833af41d4d3654
record_format	dspace
spelling	oai:doaj.org-article:29d497457f834dadb0833af41d4d36542021-12-02T15:08:17ZExploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations10.1038/s41598-018-31749-z2045-2322https://doaj.org/article/29d497457f834dadb0833af41d4d36542018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31749-zhttps://doaj.org/toc/2045-2322Abstract 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.Sang Won JungArt E. ChoWookyung YuNature PortfolioarticleCannabinoid Receptor (CB1)Ligand EfficacyMolecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA)Binding Free EnergyActive ConformationMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cannabinoid Receptor (CB1) Ligand Efficacy Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) Binding Free Energy Active Conformation Medicine R Science Q
spellingShingle	Cannabinoid Receptor (CB1) Ligand Efficacy Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) Binding Free Energy Active Conformation Medicine R Science Q Sang Won Jung Art E. Cho Wookyung Yu Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations
description	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.
format	article
author	Sang Won Jung Art E. Cho Wookyung Yu
author_facet	Sang Won Jung Art E. Cho Wookyung Yu
author_sort	Sang Won Jung
title	Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations
title_short	Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations
title_full	Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations
title_fullStr	Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations
title_full_unstemmed	Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations
title_sort	exploring the ligand efficacy of cannabinoid receptor 1 (cb1) using molecular dynamics simulations
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/29d497457f834dadb0833af41d4d3654
work_keys_str_mv	AT sangwonjung exploringtheligandefficacyofcannabinoidreceptor1cb1usingmoleculardynamicssimulations AT artecho exploringtheligandefficacyofcannabinoidreceptor1cb1usingmoleculardynamicssimulations AT wookyungyu exploringtheligandefficacyofcannabinoidreceptor1cb1usingmoleculardynamicssimulations
_version_	1718388174002061312

Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations

Ejemplares similares