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Evaluation of library ranking efficacy in virtual screening
Maria Kontoyianni1, Glenn S Sokol, Laura M McClellan
1Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Computer Assisted Drug Discovery, Welsh and McKean Roads, P.O. Box 776, Spring House, Pennsylvania 19477, USA. mkontoyi@yahoo.com
Journal of Computational Chemistry
|November 5, 2004
Summary
We evaluated how docking procedures impact virtual screening performance, finding that specific docking/scoring combinations effectively identify active compounds. Accurate poses improve scoring function accuracy, reducing false positives in drug discovery.
Area of Science:
- Computational chemistry
- Drug discovery
- Bioinformatics
Background:
- Virtual screening is crucial for identifying drug candidates.
- The accuracy of docking procedures significantly influences virtual screening efficacy.
- Optimizing docking and scoring functions is essential for reliable hit identification.
Purpose of the Study:
- To investigate the impact of docking procedures on virtual screening performance.
- To compare the effectiveness of different docking engines and scoring functions.
- To assess the role of pose accuracy in compound ranking.
Main Methods:
- Utilized four docking engines and ten scoring functions.
- Applied methods to seeded databases against six target proteins.
- Compared the ranking efficacy of various docking/scoring combinations using experimental poses.
Main Results:
- LigandFit/Ligscore1 and LigandFit/GOLD combinations showed superior performance in retrieving active compounds.
- Scoring functions ranked experimental poses higher than inaccurate poses.
- Pose accuracy enhances the discriminatory ability of scoring algorithms.
Conclusions:
- Specific docking and scoring function combinations significantly improve virtual screening success rates.
- The availability of accurate ligand poses is critical for reliable compound ranking.
- Improving pose prediction accuracy can reduce false positives in virtual screening campaigns.