We implemented a stopping criterion for both RAMD and iMetaD using the "MinDist" descriptor defined as the minimal distance between the protein atoms and the ligand atoms. In order to improve performance during the simulation, we approximate MinDist by measuring distances between four maximally spaced ligand atoms and all protein C ɑ atoms. Throughout the simulation, the MinDist is monitored and when it surpasses an 8 Å cutoff the ligand is deemed to be unbound and the simulation is terminated. This distance cutoff was selected to avoid false positives when labeling the unbound state while measuring a subset of protein-ligand distances.