Automated Docking Screens: A Feasibility Study

By John J. Irwin, Brian K. Shoichet, Michael M. Mysinger, Niu Huang, Francesco Colizzi, Pascal Wassam, Yiqun Cao. 2009

267 citations recorded by the source corpus.

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 Å 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 Å rmsd, suggesting that unsupervised prospective docking is viable. DOCK Blaster is available at http://blaster.docking.org.

Subfields: Computational Theory and Mathematics, Materials Chemistry, Molecular Biology

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Citations in the corpus

Reactome: a database of reactions, pathways and biological processes (2010, background): “This year, additional crossreferences to RSCB Protein Data Bank (34), Comparative Toxicogenomics Database (35), DockBlaster (36), BioGPS (37) and dbSNP (38) have been added to the protein pages.”
Structure-based drug screening for G-protein-coupled receptors. (2012, methodology): “Widely used docking programs include AutoDock,[47] ICM,[48] FlexX,[49] Glide,[50] and DOCK.[51, 52] A web-based, automated version of the last is available at http://blaster.”
Ligand Pose and Orientational Sampling in Molecular Docking (2013, methodology): “Target preparation for docking proceeded in a new protocol derivative of the DOCK Blaster pipeline[89].”
Challenges and advances in computational docking: 2009 in review (2011, unknown): “(129) have investigated the feasibility of such automation using their DOCK Blaster server (blaster.docking.org) and tested it for pose ﬁdelity and enrichment.”
Advances and Challenges in Protein-Ligand Docking (2010, unknown): “org/) [167,168]”
Pharmit: interactive exploration of chemical space (2016, background): “Those that exist, such as DockBlaster (2), iDrug (3), iStar (4), e-LEA3D (5) and MTiOpenScreen (6), are typically batch-processing services where the user sub-mits a virtual screening job and receives the results hours or days later.”
Rosetta FlexPepDock web server—high resolution modeling of peptide–protein interactions (2011, background): “While a plethora of web servers is available for the docking of a pair of globular proteins [e.g. RosettaDock (16), HADDOCK (17), PatchDock (18), ClusPro (19) and more; see CAPRI (20)], these are not intended for the docking of peptides.”
Theory and Applications of Covalent Docking in Drug Discovery: Merits and Pitfalls (2015, unknown): “sg/ Gold [41] Dockovalent (Covalent Docking Server) [57] http://covalent.”
SwissDock, a protein-small molecule docking web service based on EADock DSS (2011, unknown): “A large interest for docking web servers has emerged recently, as can be seen through the growing list of similar web services currently available, such as DockingServer (http://www.dockingserver.com/web), Blaster (18), DockingAtUTMB (http://docking.utmb.edu/), Pardock (http://www.scfbio-iitd.res.in”