FRED Pose Prediction and Virtual Screening Accuracy

TLDR

FRED was employed in both a conventional docking mode and a hybrid mode that incorporates the structure of a bound ligand alongside the protein to screen molecules. The analysis revealed that while most docking programs perform well overall, they are highly inconsistent across systems, with statistically significant differences in mean DUD performance observed 61 % of the time using AUC, and early enrichment metrics showing limited discriminative power (only 14 % confidence at 0.5 % enrichment).

Abstract

Results of a previous docking study are reanalyzed and extended to include results from the docking program FRED and a detailed statistical analysis of both structure reproduction and virtual screening results. FRED is run both in a traditional docking mode and in a hybrid mode that makes use of the structure of a bound ligand in addition to the protein structure to screen molecules. This analysis shows that most docking programs are effective overall but highly inconsistent, tending to do well on one system and poorly on the next. Comparing methods, the difference in mean performance on DUD is found to be statistically significant (95% confidence) 61% of the time when using a global enrichment metric (AUC). Early enrichment metrics are found to have relatively poor statistical power, with 0.5% early enrichment only able to distinguish methods to 95% confidence 14% of the time.