Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
J Comput Aided Mol Des ; 31(8): 755-775, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28712038

RESUMEN

The knowledge of the free energy of binding of small molecules to a macromolecular target is crucial in drug design as is the ability to predict the functional consequences of binding. We highlight how a molecular dynamics (MD)-based approach can be used to predict the free energy of small molecules, and to provide priorities for the synthesis and the validation via in vitro tests. Here, we study the dynamics and energetics of the nuclear receptor REV-ERBα with its co-repressor NCoR and 35 novel agonists. Our in silico approach combines molecular docking, molecular dynamics (MD), solvent-accessible surface area (SASA) and molecular mechanics poisson boltzmann surface area (MMPBSA) calculations. While docking yielded initial hints on the binding modes, their stability was assessed by MD. The SASA calculations revealed that the presence of the ligand led to a higher exposure of hydrophobic REV-ERB residues for NCoR recruitment. MMPBSA was very successful in ranking ligands by potency in a retrospective and prospective manner. Particularly, the prospective MMPBSA ranking-based validations for four compounds, three predicted to be active and one weakly active, were confirmed experimentally.


Asunto(s)
Co-Represor 1 de Receptor Nuclear/agonistas , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/agonistas , Sitios de Unión , Células HEK293 , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Co-Represor 1 de Receptor Nuclear/química , Co-Represor 1 de Receptor Nuclear/metabolismo , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/química , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/metabolismo , Unión Proteica , Conformación Proteica , Solventes , Relación Estructura-Actividad , Propiedades de Superficie , Termodinámica
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA