Figure 5.

(a) Enrichment differences between the standard scoring function and optimized scoring function comparing the new DUDE-Z benchmarks, charge extrema decoys, and the Goldilocks benchmarks, with a focus on the enrichment changes in specific targets (b). Comparison of net charge of ligands and benchmark decoys for AmpC β-lactamase (AmpC, c), GAR transformylase (PUR2, d), trypsin I (TRY1, e), peroxisome proliferator-activated receptor alpha (PPARA, f), urokinase-type plasminogen activator (UROK, g), and epidermal growth factor receptor (EGFR, h). For systems whose ligands have more extreme charges, there is a typically small overlap in ligand charges and decoy charges, providing an advantage to the extreme charged ligands with the optimized scoring function. However, in systems where the ligand charges overlap more significantly with the decoy charges, the standard scoring function begins to perform better as there are no extreme charged ligands to exploit the lower desolvation cost and rank more favorably.