Docking and three-dimensional quantitative structure-activity relationship (3D QSAR) analyses of nonsteroidal progesterone receptor ligands.
J Med Chem
; 49(14): 4261-8, 2006 Jul 13.
Article
en En
| MEDLINE
| ID: mdl-16821785
ABSTRACT
We report a docking and comparative molecular similarity indices analysis (CoMSIA) study of progesterone receptor (PR) ligands with an emphasis on nonsteroids including tanaproget. The ligand alignment generation, a critical part of model building, comprised two stages. First, thorough conformational sampling of docking poses within the PR binding pocket was made with the program GOLD. Second, a strategy to select representative poses for CoMSIA was developed utilizing the FlexX scoring function. After manual replacement of five poses where this approach had problems, a significant correlation (r(2) = 0.878) between the experimental affinities and electrostatic, hydrophobic, and hydrogen bond donor properties of the aligned ligands was found. Extensive model validation was made using random-group cross-validations, external test set predictions (r(pred)(2) = 0.833), and consistency check between the CoMSIA model and the PR binding site structure. Robustness, predictive ability, and automated alignment generation make the model a potential tool for virtual screening.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Quinolinas
/
Receptores de Progesterona
/
Relación Estructura-Actividad Cuantitativa
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Finlandia