The ten structures used in this study were initially re-refined using PHENIX-AFITT for two reasons. The first was to generate ligand bond lengths, angles and torsions fit using energetics from a small molecule force field -in this case MMFF94s. The second was to assess whether additional low occupancy conformations or binding modes existed. While the depositors were very careful and thorough in fitting the ligands for these structures there is prior evidence, from the recent qFit publication by G. C. P. van Zundert et al., that up to 29% of protein-ligand complexes could have ligand heterogeneity or unmodeled alternate binding modes. Our initial analysis suggested some of the ten structures had evidence of alternate binding modes, making them an ideal test cases for a method geared towards sampling of binding modes. We used a method based on AFITT but similar in principle to qFit and found three cases of previously unmodeled heterogeneity. They were a missing alternate conformation for TGX, a different binding conformation for 6N6, and an additional binding mode for GVG. For 6N6 the new conformation rotates the thiodiazol-2-amine ring by 180 • into an orientation with better interactions with the protein but the thiophene ring is left in a higher energy conformation (see Figure ). This new conformation had the highest RMSD difference (1.4 Å) to the deposited structure for all the ligands in this set. For 6N6 an alternate and possibly better model would have rotated the thiophene ring or added an alternate conformation for the thiophene. It is interesting to note that the amount of heterogeneity was for this small data set was 30%, which is very similar to the 29% reported by G. C. P. van Zundert et al.