KinFragLib

KinFragLib constructs kinase-focused fragment libraries and recombination libraries from KLIFS structural data (over 2,500 kinase DFG-in complexes) to enable fragment-based exploration and design of protein kinase inhibitors.

Key Features:

• Data-driven fragmentation: Fragments co-crystallized non-covalent kinase inhibitors are generated by three-dimensional proximity to six predefined subpocket centers.
• Subpocket-focused fragment library: The library comprises over 7,000 fragments distributed across six subpocket pools derived from KLIFS data.
• Chemical space exploration: Enables analysis of subpocket characteristics and connections to probe the chemical space of kinase inhibitors.
• Subpocket-informed recombination: Recombines a subset of 624 representative fragments to generate approximately 6.7 million molecules, of which >99% are novel relative to ChEMBL and 63% comply with Lipinski's rule of five.

Scientific Applications:

• Kinase inhibitor discovery: Aids identification of novel protein kinase inhibitors by expanding chemical space through subpocket-specific fragment recombination.

Methodology:

Utilizing structural data from the KLIFS database.
Fragmenting co-crystallized non-covalent inhibitors based on spatial proximity to six predefined subpocket centers.
Recombining fragments to explore new chemical entities and potential drug candidates.