Read about KinFragLib in JCIM
2020.11.06 · By Dominique Sydow
Our KinFragLib project is now published in the Journal of Chemical Modeling and Information: “KinFragLib: Exploring the Kinase Inhibitor Space Using Subpocket-Focused Fragmentation and Recombination” (DOI: 10.1021/acs.jcim.0c00839).
Kinases are one of the most studied drug targets, resulting in an amount of available data too large to be analyzed manually. In the KinFragLib project, a precise cartography of the ATP-binding site guides the fragmentation of cocrystallized kinase ligands by subpockets. The resulting kinase-focused fragment library allows the analysis of the chemical space by subpocket and is a rich source of inspiration for building novel kinase inhibitors.
Subpocket-guided recombination of a divers subset of fragments generated a combinatorial library of over 6 million molecules with over 99.99% of novel chemical matter (compared to ChEMBL 25). The rare exceptions of known compounds include predominately known kinase inhibitors. These results clearly highlight the enormous potential of this fragment library for the design of novel kinase inhibitors.
All KinFragLib resources at a glance:
- KinFragLib project website: The project overview.
- KinFragLib publication: The methodology and results.
- KinFragLib GitHub repository: The fragment and combinatorial libraries including all analyses notebooks.
Thanks again to Dominique Sydow and Paula Schmiel (co-first authors) as well as Jérémie Mortier and Andrea Volkamer for their work on this project!