title: Automated docking screens: a feasibility study.
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 .
authors.affiliation: Department of Pharmaceutical Chemistry, Byers Hall, Box 2550, University of California San Francisco, San Francisco, California 94158-2330, USA. jji@cgl.ucsf.edu
authors.forename: John J
authors.initials: JJ
authors.lastname: Irwin
authors.forename: Brian K
authors.initials: BK
authors.lastname: Shoichet
authors.forename: Michael M
authors.initials: MM
authors.lastname: Mysinger
authors.forename: Niu
authors.initials: N
authors.lastname: Huang
authors.forename: Francesco
authors.initials: F
authors.lastname: Colizzi
authors.forename: Pascal
authors.initials: P
authors.lastname: Wassam
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Cao
mesh_terms: D001331:Automation; D019985:Benchmarking; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005240:Feasibility Studies; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D008024:Ligands; D011506:Proteins