Variability in docking success rates due to dataset preparation

By Christopher R. Corbeil, C. Williams, Paul Labute. 2012

413 citations recorded by the source corpus.

The results of cognate docking with the prepared Astex dataset provided by the organizers of the “Docking and Scoring: A Review of Docking Programs” session at the 241st ACS national meeting are presented. The MOE software with the newly developed GBVI/WSA dG scoring function is used throughout the study. For 80 % of the Astex targets, the MOE docker produces a top-scoring pose within 2 Å of the X-ray structure. For 91 % of the targets a pose within 2 Å of the X-ray structure is produced in the top 30 poses. Docking failures, defined as cases where the top scoring pose is greater than 2 Å from the experimental structure, are shown to be largely due to the absence of bound waters in the source dataset, highlighting the need to include these and other crucial information in future standardized sets. Docking success is shown to depend heavily on data preparation. A “dataset preparation” error of 0.5 kcal/mol is shown to cause fluctuations of over 20 % in docking success rates.

Subfields: Radiation, Radiology, Nuclear Medicine and Imaging, Computational Chemistry & Drug Discovery

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Citations in the corpus

• Molecular Docking and Structure-Based Drug Design Strategies (2015, methodology): “…eHiTS [28] AutoDock [34] FRED [30] Gold [35] Surflex-Dock [31] PRO_LEADS [44] DOCK [32] EADock [45] GLIDE [37] ICM [46] EUDOC [38] LigandFit [47] FlexX [39] Molegro Virtual Docker [48] Hammerhead [40] CDocker [49] Flog [41] GlamDock [50] SLIDE [42] PLANTS [51] ADAM [43] MolDock [52] MOE_Dock [53]”
• Software for molecular docking: a review (2017, methodology): “> MOE-Dock (45.6%).”
• Bridging Molecular Docking to Molecular Dynamics in Exploring Ligand-Protein Recognition Process: An Overview (2018, background): “Examples of force field based scoring functions are GoldScore (Verdonk et al., 2003), AutoDock (Morris et al., 1998) (improved as a semiempirical version in AutoDock4, Huey et al., 2007), GBVI/WSA (Corbeil et al., 2012).”
• A practical guide to large-scale docking (2021, methodology): “There are by now multiple widely used and effective docking programs 23 – 31 , employing different strategies for sampling ligand orientations and ligand conformations in the protein site, for handling protein fl exibility, and for scoring ligand fi t once they have been docked.”
• Structure-Based Virtual Screening for Drug Discovery: Principles, Applications and Recent Advances (2014, positive): “Several protocols are considered and applied on the Directory of Useful Decoys (DUD) database [27, 28], showing that database enrichment is improved after proper receptor preparation and that neglecting certain steps of the preparation process produces a systematic degradation in enrichments, which ”