How KinaDB classifies kinase activation state
KinaDB brings together 8,626 kinase structures, their predicted activation states, and 85 kinase-inhibitor drugs. Every structure carries an Active / Inactive call derived from its conformation — here is how that call is made.
The activation segment as a switch
Every protein kinase has an activation segment — a short, flexible stretch that acts like a molecular switch. When a kinase is "on," this segment folds into a specific shape that lines up the machinery needed to transfer a phosphate group from ATP; when it's "off," the segment collapses into a different, incompatible shape.
We represent the activation segment as a simple path through 3D space, one point per residue, and compute the vectors and angles between consecutive residues — describing how the backbone bends and twists at each step. A model trained on this geometric fingerprint, rather than manual inspection, produces the Active / Inactive call shown on every structure page.
Two structural markers: DFG and the αC-helix
The DFG motif (Asp-Phe-Gly) sits at the start of the activation loop. In the DFG-in state the aspartate points into the ATP pocket, ready for catalysis; in DFG-out it swings away, a hallmark of inactive and Type-II-inhibitor-bound structures.
The αC-helix is a second, independent marker. In the αC-in state a conserved Lys–Glu salt bridge forms and the catalytic residues align; αC-out breaks that arrangement. KinaDB reports both the consensus DFG and αC-helix conformation, and — following the KinCore method — whether the regulatory salt bridge is present.
Because both markers vary independently, they combine into the 2×2 above: only DFG-in and αC-in is confidently active; the opposite corner is inactive; the mixed corners are intermediate.
Across the current database
You can see the call, the confidence, and both conformation markers on any structure page, or read the field-by-field definitions in the documentation.