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Evaluation of a novel shape-based computational filter for lead evolution: application to thrombin inhibitors
Jayashree Srinivasan1, Angelo Castellino, Erin K Bradley
1Deltagen Research Laboratories, 4570 Executive Drive, Suite 400, San Diego, CA 92121, USA. jsrinivasan@deltagen.com
Journal of Medicinal Chemistry
|May 31, 2002
Summary
A new computational method uses molecular shapes and features to quickly screen compound libraries. This approach efficiently identifies promising novel drug scaffolds with improved hit rates.
Area of Science:
- Computational chemistry
- Drug discovery
- cheminformatics
Background:
- Drug discovery relies on efficient screening of large compound libraries.
- Identifying novel scaffolds with high hit rates is crucial for lead optimization.
Purpose of the Study:
- To develop and validate a novel shape-feature-based computational method for rapid compound library filtering.
- To assess the method's efficiency in identifying novel scaffolds with enhanced hit rates.
Main Methods:
- A computational model was developed using 3D conformations of active and inactive molecules.
- The model incorporates whole molecule shapes and chemical feature positions, ranked by activity correlation.
- A small ensemble of these features was used to filter virtual compound libraries.
Main Results:
- The method was applied to two thrombin data sets.
- It demonstrated efficiency in identifying novel scaffolds.
- Enhanced hit rates were observed in the filtered libraries.
Conclusions:
- The described shape-feature-based computational method is effective for rapid compound library screening.
- This approach facilitates the identification of novel scaffolds with improved drug discovery potential.