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J Med Chem. 2009 Sep 24;52(18):5712-20. doi: 10.1021/jm9006966.

Automated docking screens: a feasibility study.

Author information

1
Department of Pharmaceutical Chemistry, Byers Hall, Box 2550, University of California San Francisco, San Francisco, California 94158-2330, USA. jji@cgl.ucsf.edu

Abstract

Molecular 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 A rmsd 50-60% of the time; inferior to an expert, but respectrable. 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 7755 eligible PDB structures. In 1398 cases, the redocked ligand ranked in the top 5% of 100 property-matched decoys while also posing within 2 A rmsd, suggesting that unsupervised prospective docking is viable. DOCK Blaster is available at http://blaster.docking.org .

PMID:
19719084
PMCID:
PMC2745826
DOI:
10.1021/jm9006966
[Indexed for MEDLINE]
Free PMC Article

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