Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein-Ligand Binding.
J Chem Theory Comput
; 17(4): 2630-2639, 2021 Apr 13.
Article
en En
| MEDLINE
| ID: mdl-33779166
ABSTRACT
We present a reliable and accurate solution to the induced fit docking problem for protein-ligand binding by combining ligand-based pharmacophore docking, rigid receptor docking, and protein structure prediction with explicit solvent molecular dynamics simulations. This novel methodology in detailed retrospective and prospective testing succeeded to determine protein-ligand binding modes with a root-mean-square deviation within 2.5 Å in over 90% of cross-docking cases. We further demonstrate these predicted ligand-receptor structures were sufficiently accurate to prospectively enable predictive structure-based drug discovery for challenging targets, substantially expanding the domain of applicability for such methods.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas
/
Simulación del Acoplamiento Molecular
Idioma:
En
Revista:
J Chem Theory Comput
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos