Structure-based docking is the most practical approach to leverage protein structure for ligand discovery, but the technique retains important liabilities that make it challenging to deploy on a large scale. We have therefore created an expert system, DOCK Blaster, to investigate the feasibility of full automation. The method requires a PDB code, sometimes with a ligand structure, and from that alone can launch a full screen of large libraries. A critical feature is self-assessment, which estimates the anticipated reliability of the automated screening results using pose fidelity and enrichment. Against common benchmarks, DOCK Blaster recapitulates the crystal ligand pose within 2� RMSD 50-60% of the time; inferior to an expert, but respectable. Half the time the ligand also ranked among the top 5% of 100 physically-matched decoys chosen on the fly. Further tests were undertaken culminating in a study of 7,755 eligible PDB structures. In 1,398 cases the re-docked ligand ranked in the top 5% of 100 property-matched decoys while also posing within 2� RMSD, suggesting that unsupervised prospective docking is viable. DOCK Blaster is available at http://blaster.docking.org.

Automated docking screens: A feasibility study

239th National Meeting (2010)

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