To accurately estimate residence time, we employ a multi-step workflow as outlined in Figure . In this workflow, following system preparation and equilibration, we generate an ensemble of unbinding trajectories with RAMD which explore various egress paths. Subsequently, we parametrize trajectories as paths composed of summary waypoints and apply clustering to identify the most frequently traversed path. This is used to define a custom set of CVs that capture the essential features of the ligand unbinding process. Finally, iMetaD utilizes the identified CVs to accelerate unbinding and provide an estimate of the residence time.