1.
J Chem Inf Model
; 54(2): 362-6, 2014 Feb 24.
Artigo
em Inglês
| MEDLINE
| ID: mdl-24444037
RESUMO
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.