KinaFrag

KinaFrag curates 31,464 fragments derived from reported kinase inhibitors and organizes structural, physicochemical, similarity, and substructure data to support fragment-based design of selective protein kinase inhibitors.

Key Features:

• Fragment collection: Contains 31,464 fragments derived from reported kinase inhibitors.
• Crystal fragment structures: Includes 3,244 crystal fragment structures and 7,783 crystal kinase-fragment complexes.
• Structural organization: Structures are organized by binding clefts and subpockets to enable inspection of three-dimensional fragment–kinase interactions.
• Physicochemical information: Provides detailed physicochemical profiles for each fragment.
• Similarity metrics and substructure relationships: Supplies similarity scores and substructure relationships to compare and relate fragments.
• Fragment-based design strategies: Supports fragment-based drug design analyses and workflows.
• Computational fragment growing: Implements a computational fragment growing strategy developed by the research group at Central China Normal University (CCNU).
• Demonstrated lead optimization: Has been used to develop a lead compound targeting c-Met kinase with an approximately ~1000-fold improvement in in vitro activity over the initial hit.

Scientific Applications:

• Fragment-based kinase inhibitor discovery: Identification of fragment starting points for selective protein kinase inhibitor development.
• Structure–activity analysis: Analysis of fragment–kinase interactions within defined binding clefts and subpockets to inform SAR interpretation.
• Lead optimization via fragment growing: Application of computational fragment growing to evolve fragments into optimized leads, exemplified by the c-Met kinase case.
• Comparative fragment analysis: Use of similarity metrics and substructure relationships to compare and prioritize fragments for medicinal chemistry follow-up.

Methodology:

Implementation and testing of a computational fragment growing strategy developed by the CCNU research group using the compiled fragment libraries.