Optimization of CAMD techniques 3. Virtual screening enrichment studies: a help or hindrance in tool selection?

@article{Good2008OptimizationOC,
  title={Optimization of CAMD techniques 3. Virtual screening enrichment studies: a help or hindrance in tool selection?},
  author={Andrew C. Good and Tudor I. Oprea},
  journal={Journal of Computer-Aided Molecular Design},
  year={2008},
  volume={22},
  pages={169-178}
}
  • A. Good, T. Oprea
  • Published 9 January 2008
  • Computer Science, Medicine
  • Journal of Computer-Aided Molecular Design
Over the last few years many articles have been published in an attempt to provide performance benchmarks for virtual screening tools. While this research has imparted useful insights, the myriad variables controlling said studies place significant limits on results interpretability. Here we investigate the effects of these variables, including analysis of calculation setup variation, the effect of target choice, active/decoy set selection (with particular emphasis on the effect of analogue… 
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References

SHOWING 1-10 OF 36 REFERENCES
Measuring CAMD technique performance: A virtual screening case study in the design of validation experiments
TLDR
This work addresses the issue for ligand-based virtual screening descriptors through design of validation experiments that better reflect the aims of real world application and Guidelines for optimal application of said descriptors are discussed.
Comparison of Topological, Shape, and Docking Methods in Virtual Screening
TLDR
Averaged over multiple targets, ligand-based methods outperformed docking algorithms, and Glide appears to be the best docking method among the three with FRED a close second.
Target-biased scoring approaches and expert systems in structure-based virtual screening.
Structure-based virtual screening followed by selection of a top fraction of the rank-ordered result list suffers from many false positives and false negatives because the general scoring functions
Analysis and optimization of structure-based virtual screening protocols. (3). New methods and old problems in scoring function design.
TLDR
An alternative method for scoring function design is presented that attempts to combine crystallographic structural information with data derived from directly within SVS calculations that utilizes a genetic algorithm to optimize functions based on binding property dataderived from multiple virtual screening calculations.
Comparison of shape-matching and docking as virtual screening tools.
TLDR
The results show that a shape-based, ligand-centric approach is more consistent than, and often superior to, the protein-focused approach taken by docking.
On Evaluating Molecular-Docking Methods for Pose Prediction and Enrichment Factors
TLDR
Four of the most well-known, commercially available docking programs, FlexX, GOLD, GLIDE, and ICM, have been examined for their ligand-docking and virtual-screening capabilities and the capability of the four programs to correctly rank-order target-specific active compounds over alternative binders and nonbinders and thereby enrich a small subset of a screening library is compared.
Comparison of automated docking programs as virtual screening tools.
TLDR
For a given docking method, hit rates were improved versus what would be expected for random selection for most protein targets, but the ability to prioritize known ligands on the basis of docking poses that resemble known crystal structures is both method- and target-dependent.
Ranking poses in structure-based lead discovery and optimization: current trends in scoring function development.
  • R. Rajamani, A. Good
  • Computer Science, Medicine
    Current opinion in drug discovery & development
  • 2007
TLDR
There is an abundance of new research in the field of scoring function design, from incorporation of novel descriptors (derived from first principles or empirical analysis) to function redesign based on improved data set handling.
Fast structure-based virtual ligand screening combining FRED, DOCK, and Surflex.
TLDR
The present protocol could process the entire bank for one receptor in less than a week on one processor, suggesting that VLS experiments could be performed even without large computer resources.
Docking and scoring in virtual screening for drug discovery: methods and applications
TLDR
Key concepts and specific features of small-molecule–protein docking methods are reviewed, selected applications are highlighted and recent advances that aim to address the acknowledged limitations of established approaches are discussed.
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1
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