Evaluation of DOCK 6 as a pose generation and data

Authors: Scott R Brozell Sudipto Mukherjee Trent E Balius Daniel R Roe David A Case Robert C Rizzo

Publish Date: 2012/05/09

Volume: 26, Issue: 6, Pages: 749-773

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Abstract

In conjunction with the recent American Chemical Society symposium titled “Docking and Scoring A Review of Docking Programs” the performance of the DOCK6 program was evaluated through 1 pose reproduction and 2 database enrichment calculations on a common set of organizerspecified systems and datasets ASTEX DUD WOMBAT Representative baseline grid score results averaged over five docking runs yield a relatively high pose identification success rate of 725  symmetry corrected rmsd and sampling rate of 919  for the multi site ASTEX set N = 147 using organizersupplied structures Numerous additional docking experiments showed that ligand starting conditions symmetry multiple binding sites clustering and receptor preparation protocols all affect success Encouragingly in some cases use of more sophisticated scoring and sampling methods yielded results which were comparable Amber score ligand movable protocol or exceeded LMOD score analogous baseline gridscore results The analysis highlights the potential benefit and challenges associated with including receptor flexibility and indicates that different scoring functions have system dependent strengths and weaknesses Enrichment studies with the DUD database prepared using the SB2010 preparation protocol and native ligand pairings yielded individual area under the curve AUC values derived from receiver operating characteristic curve analysis ranging from 029 bad enrichment to 096 good enrichment with an average value of 060 27/38 have AUC ≥ 05 Strong early enrichment was also observed in the critically important 10–20  region Somewhat surprisingly an alternative receptor preparation protocol yielded comparable results As expected semirandom pairings yielded poorer enrichments in particular for unrelated receptors Overall the breadth and number of experiments performed provide a useful snapshot of current capabilities of DOCK6 as well as starting points to guide future development efforts to further improve sampling and scoringGreg Warren Neysa Nevins and Georgia McGauhey are thanked for organizing the special Docking and Scoring symposium William J Allen and Jiangyang Liu are thanked for code development and Steve Skiena is thanked for helpful discussions regarding implementation of symmetry corrected rmsd using the Hungarian matching algorithm This work was supported in part by NIH grants GM57513 DAC R01GM083669 RCR and F31CA134201 TEB as well as the Stony Brook University Office of the Vice President for Research and the New York State Office of Science Technology and Academic Research NYSTAR SRB gratefully acknowledges the use of computational facilities at the Ohio Supercomputer Center and thanks OpenEye Scientific Software for an academic license This work also used resources at the New York Center for Computational Sciences at Stony Brook University/Brookhaven National Laboratory supported by the US Department of Energy under Contract No DEAC0298CH10886 and by the State of New York Molecular graphics and analyses were performed with the UCSF Chimera package Chimera is developed by the Resource for Biocomputing Visualization and Informatics at the University of California San Francisco with support from the National Institutes of Health National Center for Research Resources grant 2P41RR001081 National Institute of General Medical Sciences grant 9P41GM103311

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