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Molecular Scaffold Hopping via Holistic Molecular Representation
Francesca Grisoni1, Gisbert Schneider2
1Department of Chemistry and Applied Biosciences, RETHINK, ETH Zurich, Zurich, Switzerland. francesca.grisoni@pharma.ethz.ch.
Methods in Molecular Biology (Clifton, N.J.)
|March 24, 2021
Summary
This study introduces Weighted Holistic Atom Localization and Entity Shape (WHALES) descriptors for computer-assisted drug discovery. These descriptors aid in virtual screening and scaffold hopping by capturing molecular shape and charge.
Area of Science:
- Computational chemistry
- Cheminformatics
- Drug discovery
Background:
- Molecular descriptors are crucial for computer-assisted drug discovery.
- Existing methods may not fully capture essential molecular properties for scaffold hopping.
- Natural products offer rich scaffolds but require translation to synthetic molecules.
Purpose of the Study:
- To introduce and explain the Weighted Holistic Atom Localization and Entity Shape (WHALES) descriptors.
- To demonstrate the application of WHALES descriptors in virtual compound screening.
- To facilitate scaffold hopping from natural products to synthetic molecules using WHALES.
Main Methods:
- Utilizing WHALES descriptors that encode molecular shape and partial charges simultaneously.
- Applying WHALES descriptors for virtual compound screening workflows.
- Implementing a step-by-step guide for scaffold hopping with WHALES.
Main Results:
- WHALES descriptors effectively capture both shape and electronic properties.
- Successful application demonstrated for virtual screening and scaffold hopping tasks.
- Reproducible results achieved using freely available code.
Conclusions:
- WHALES descriptors provide a powerful tool for molecular representation in drug discovery.
- The method enhances scaffold hopping strategies, bridging natural products and synthetic chemistry.
- Open-source code availability promotes wider adoption and further research.
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