Here, we find that no method always correctly identifies the crystallographic binding mode (as evidenced by average RMSD) but both MD and BLUES substantially outperform docking at sampling binding modes near the crystallographic one, and of these, BLUES performs better. From Table , we see that docking was only able to generate poses which were within 2Å of the crystallographic structure in 2/29 (7%) cases and was close (within 4Å ) in 12/29 (41%) cases. To remind the reader, when we evaluate the sampling proficiency for MD and BLUES, we consider the method successful when the top two most populated binding modes (or top three if there are 3 or more crystallographic binding modes) contain a sample which is within 2Å of the crystal structure (Table ). Across the all the molecules used in this study, Averaged across all of the ligands in this study, the minimum RMSDs for docking (pink), MD (lime), and BLUES (cyan) were 3.9 ± 0.2Å, 1.4 ± 0.2Å, and 1.0 ± 0.1Å respectively;