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Updated: Aug 5, 2025
Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay
Published on: February 28, 2025
SCARdock: A Web Server and Manually Curated Resource for Discovering Covalent Ligands
Qi Song1,2, Lingyu Zeng1,2, Qiang Zheng1,2
1Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province) & Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, China.
Covalent drugs offer advantages like improved efficiency and specificity. A new web server and datasets, based on the steric-clashes alleviating receptor (SCAR) strategy, accelerate covalent ligand discovery.
Area of Science:
- Drug Discovery
- Medicinal Chemistry
- Computational Chemistry
Background:
- Covalent drugs, historically avoided due to side effect concerns, are experiencing a resurgence.
- Covalent ligands offer potential advantages over noncovalent ligands, including enhanced biochemical efficiency and specificity.
Purpose of the Study:
- To facilitate the discovery and repurposing of covalent inhibitors.
- To provide researchers with accessible tools and curated data for covalent drug design.
Main Methods:
- Development of the SCARdock web server implementing the steric-clashes alleviating receptor (SCAR) strategy.
- Creation of three comprehensive datasets for covalent ligand discovery.
Main Results:
- A manually curated dataset of 954 covalent ligand-protein complex structures.
- A dataset of 68 experimentally confirmed covalent warheads targeting 11 distinct residues.
- A prefiltered dataset of 690,018 purchasable virtual compounds with verified warheads.
Conclusions:
- The SCARdock server and associated datasets are valuable resources for advancing covalent ligand discovery.
- These resources are freely available to the scientific community to accelerate research.
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