In the case of MD, the simulations have a tendency to stabilize into a binding mode which is close to the crystal structure, rather than sampling close to the crystallographic structure. In general, we believe this may be due to the forcefield disagreeing with some of the crystal structure-particularly in the case of 6TZ. This discrepancy could also be because of differences in conditions (crystallographic structures being collected at cryogenic temperatures, for example, and in the environment of a crystal). Clusters for molecules which have a single binding mode have an overall average RMSD of 3.4 ± 0.9Å from MD and 3.0 ± 0.6Å from BLUES, while clusters for molecules with multiple binding modes have an overall average RMSD of 5.9 ± 0.5Å from MD and 5.0 ± 0.3Å . We believe that the higher average RMSD for multiple binding mode molecules (6TZ, GVG, KUF) may suggest that converged forcefield results disagree with the crystallographic binding modes. This may indicate deficiencies in the forcefield or differences in simulation conditions relative to crystallographic conditions, as discussed above.