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 β-lactamase. Only one of the crystallographic binding poses was found to be thermodynamically favorable, however the ligand shows several binding poses within the pocket. We also identified a deeper binding pose with a residence time comparable to the crystal pose. This study demonstrates free-binding molecular simulations in the context of fragment-to-lead development and its potential application in drug design.