Figure 8.

Schematic of the informatics infrastructure used to automatically provide the GLR reference structure, if available, as one component of the refinement pipeline. Steps outlined with dashed lines are pre-calculated. Steps outlined with solid lines are calculated for the target ligand as part of the structure refinement. A procedure based on atom pairs was used to calculate the ligand fingerprints (Carhart et al., 1985 ▶). These digital fingerprints were then compared through their pairwise Tanimoto coefficient. A coefficient threshold of 0.7 was used because ligands with this degree of similarity were found to reliably bind in the expected fashion (i.e. with the same orientation and similar overall conformation). With diverse sets of ligands, it may be necessary to lower this threshold at the risk of false positives.