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Updated: Jun 19, 2026
10:58
Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Bioactive conformational biasing: a new method for focusing conformational ensembles on bioactive-like conformers
Boaz Musafia1, Hanoch Senderowitz
1Epix Pharmaceuticals Ltd., 3 Hayetzira St., Ramat Gan 52521, Israel.
Journal of Chemical Information and Modeling
|October 15, 2009
Summary
A new filtration tool efficiently reduces ligand conformations for drug discovery. It prioritizes bioactive-like conformations, saving computational resources and improving lead optimization.
Area of Science:
- Computational chemistry
- Medicinal chemistry
- Drug discovery
Background:
- Ligand-based computational approaches require extensive analysis of numerous compound conformations.
- Reducing the computational burden in lead discovery and optimization is crucial.
Purpose of the Study:
- To develop a novel filtration tool to reduce the number of ligand conformations analyzed.
- To retain bioactive-like conformations while decreasing computational resources.
Main Methods:
- A two-step filtration process: prefiltration and filtration using 2D/3D ligand properties.
- Development and testing of multiple filtration models on training and independent test sets of drug compounds.
Main Results:
- The best models achieved an 80% success rate on the test set.
- Reduced total conformations by 36% while preserving bioactive-like conformations.
- Decreased nonbioactive conformations by 39%.
Conclusions:
- The filtration tool effectively reduces computational costs in drug discovery.
- Prefiltration significantly impacts model performance.
- The tool successfully prioritizes relevant ligand conformations for optimization.
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