Specific interactions between 2-trans enoyl-acyl carrier protein reductase and its ligand: Protein-ligand docking and ab initio fragment molecular orbital calculations.
J Mol Graph Model
; 88: 299-308, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30826710
ABSTRACT
2-trans enoyl-acyl carrier protein reductase (InhA) has been identified as a promising target for the development of novel chemotherapy for tuberculosis. In the present study, a series of heteroaryl benzamide derivatives were selected as potent inhibitors against InhA, and their binding properties with InhA were investigated at atomic and electronic levels by ab initio molecular simulations based on protein-ligand docking, classical molecular mechanics optimizations and ab initio fragment molecular orbital (FMO) calculations. The results evaluated by FMO highlight some key interactions between InhA and the derivatives, indicating that the most potent derivative has strong hydrogen bonds with the Met98 side chain of InhA and strong electrostatic interactions with the nicotinamide adenine dinucleotide cofactor. These findings provide informative structural concepts for designing novel heteroaryl benzamide derivatives with higher binding affinity to InhA.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxirredutases
/
Proteína de Transporte de Acila
/
Simulação de Dinâmica Molecular
/
Simulação de Acoplamento Molecular
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Mol Graph Model
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Tailândia