To compare generated conformers to the experimental crystal structure we use obrms from the Open Babel toolkit, 45 which properly handles internal symmetries by reporting the lowest possible root mean squared deviation (RMSD) of any valid atom matching. In all cases, the minimized RMSD (-m option) is reported (i.e., the structures are optimally aligned before calculating the RMSD). For a variety of ensemble sizes (number of samples of the specified method) we evaluate the fraction of the dataset where a conformer exists within the ensemble for a specified RMSD threshold. That is, we consider the best possible RMSD across the ensemble. Results for a variable threshold are shown in Figure with more ensemble sizes shown for two fixed thresholds, 1.0 Å and 2.0 Å in Figure . In general, we find that RDKit consistently matches or outperforms DMCG at conformer retrieval at every RMSD threshold (a more direct visual comparison is found in Figure ). This advantage is greater on the PDBbind dataset as RDKit better handles larger, more flexible ligands (Figure ). The larger, more flexible ligands in the PDBbind dataset result in consistently lower retrieval rates for both methods, but the trends between the two datasets are consistent. Energy minimization has a small, not always beneficial, effect that is more pronounced and generally beneficial for DMCG. Unless otherwise specified, we limit ourselves to evaluating minimized conformers for the remainder of our analysis.