Kinetic characterization of fragment binding in AmpC ß-lactamase by high-throughput molecular simulations.
J Chem Inf Model
; 54(2): 362-6, 2014 Feb 24.
Article
em En
| MEDLINE
| ID: mdl-24444037
ABSTRACT
Small molecules used in fragment-based drug discovery form multiple, promiscuous binding complexes difficult to capture experimentally. Here, we identify such binding poses and their associated energetics and kinetics using molecular dynamics simulations on AmpC ß-lactamase. Only one of the crystallographic binding poses was found to be thermodynamically favorable; however, the ligand shows several binding poses within the pocket. This study demonstrates free-binding molecular simulations in the context of fragment-to-lead development and its potential application in drug design.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
3_ND
Problema de saúde:
3_neglected_diseases
/
3_zoonosis
Assunto principal:
Proteínas de Bactérias
/
Beta-Lactamases
/
Bibliotecas de Moléculas Pequenas
/
Simulação de Dinâmica Molecular
/
Ensaios de Triagem em Larga Escala
Idioma:
En
Revista:
J Chem Inf Model
Assunto da revista:
INFORMATICA MEDICA
/
QUIMICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Itália