Kincore

Kincore classifies protein kinase structures from the Protein Data Bank by activation-loop conformation and annotates associated inhibitor types to support structural analysis and inhibitor design.

Key Features:

• Conformational Classification: Categorizes activation-loop conformations into eight classes based on dihedral angles that position the phenylalanine (Phe) side chain of the DFG motif at the N-terminus of the activation loop.
• Structural Correlations: Links conformational classes to the placement of the activation loop, the C-helix, and other structural elements of kinases.
• Inhibitor Type Annotation: Integrates conformational states with annotations for five inhibitor types: Type 1, Type 1.5, Type 2, Type 3, and allosteric inhibitors.
• PDB-based Dataset: Compiles and analyzes kinase structures derived from the Protein Data Bank (PDB).
• Conformational Labeling: Assigns conformational labels to kinase structures based on defined geometric criteria of the activation loop and DFG motif.

Scientific Applications:

• Conformational Dynamics Studies: Supports analysis of protein kinase conformational dynamics relevant to cellular signaling pathways.
• Rational Inhibitor Design: Informs design and development of kinase inhibitors targeting specific kinase conformations.
• Drug Discovery and Target Identification: Facilitates identification of conformation-specific therapeutic targets and optimization of inhibitor strategies.

Methodology:

Kinase structures from the PDB are clustered based on activation-loop dihedral angles that position the DFG Phe side chain to define eight conformational classes, and these conformational states are integrated with inhibitor-type annotations.