Particularly, we compute the minimum RMSD to the crystallographic structure, as well as the average RMSD of the selected representative frames of the macrostate or remaining (MDS-RMSD filtered) docked poses. Here, our reported average RMSD is calculated by averaging over 10,000 randomly drawn (with replacement) values from the remaining docked poses or 50 simulation frames which we saved to represent each binding mode. We believe our reported 'average' RMSD best represents random selection of a single docked pose from a pool of poses or a single representative frame of a macrostate to compare against the crystallographic structure. Dominant binding modes observed in simulations may disagree with crystallographic binding modes for multiple reasons; in this work, our main focus is on sampling, but force field errors can also lead to disagreements. Our data can help distinguish between disagreements caused by insufficient sampling and those caused by force field errors. Particularly, the reported average RMSD from our simulations for the binding mode closest to the crystallographic one helps us diagnose the source of error. That is, if we see a low average RMSD, the binding mode determined by our clustering approach is not only well defined but also closely agrees with the binding mode found within the crystal structure. On the other hand, a higher average RMSD -with a minimum RMSD which is low -may indicate that the binding mode determined from clustering is poorly defined or does not precisely correspond with the crystallographic binding mode, even though it is close. For example, in Figure we see that from the 2nd to last simulation, the cyan cluster has a minimum RMSD of 0.3Å to the crystallographic structure but the average RMSD of this cluster is 3.0Å (Fig. , Table ). This suggests that clustering of this binding mode may not be well defined or does not precisely correspond with the crystallographic binding mode, but we are still able to sample close to the crystallographic binding mode. In such cases, this may mean that there is a force field or model error not directly related to sampling -though we are sampling the crystallographic binding mode, our predicted dominant binding mode is not that close to it, so perhaps crystal conditions or temperature alter the preferred binding mode slightly, or our force field does not adequately represent reality.