FlexiFit
A binding pocket is often drawn as a rigid keyhole waiting for exactly one key. Real pockets are usually softer than that: a ligand is jostled in, and when a shape fits it sticks — and the pocket often reshapes around it (this is called induced fit). Predict, for each real enzyme, whether its pocket is a rigid keyhole or reshapes on contact, then watch the motion. Everything runs locally; nothing about you is collected.
This is the tool. The enzymes are listed below (works without JavaScript). A native version, when it ships, adds offline use; it never gates the web.
Loading the game… If it does not start, the guide below still works.
How to play. Press Start. Predict Rigid keyhole or Reshapes on contact (buttons or keys 1/R, 2/F). The real motion is revealed and your call is scored. Press Enter or Next. There is no way to lose.
Why the reshaping matters
When glucose binds hexokinase, the enzyme's two lobes close around it; the classic evidence came from yeast hexokinase, and it is the textbook case of Koshland's induced fit. Closing shuts water out of the active site, so ATP's phosphate is transferred to glucose rather than to water. Adenylate kinase shows the same idea: its LID domain closes over the bound ATP.
Why pockets are not rigid keyholes
The old "lock and key" picture says a pocket is a fixed slot for one exact key. Often it is closer to a hand closing around an object: a ligand is jostled into the neighbourhood, a shape fits and sticks, and the pocket reshapes to grip it (induced fit). Lock-and-key does happen, but the rigid-keyhole picture as a rule is the oversimplification this game corrects. Two of the six proteins here (carbonic anhydrase II and trypsin) do have a mostly preformed pocket, so read each pocket rather than guessing one answer.
The enzymes
Answer key — open it after you play
| Enzyme | Binds | How the pocket behaves |
|---|---|---|
| Hexokinase HK1 · P19367 | glucose | Two lobes close over glucose in the cleft. |
| Adenylate kinase AK1 · P00568 | ATP / AMP | LID + NMP domains fold down over the nucleotides. |
| Dihydrofolate reductase DHFR · P00374 | folate + NADPH | Active-site loops shift through the cycle. |
| Calmodulin CALM1 · P0DP23 | a target helix | Both lobes close around the target peptide. |
| Carbonic anhydrase II CA2 · P00918 | CO₂ and sulfonamide drugs | Mostly preformed: the zinc cleft is already shaped; drugs fit with small side-chain adjustments. |
| Trypsin PRSS1 · P07477 | a lysine or arginine side chain | Mostly preformed: the S1 pocket is already formed in the active enzyme. |
Methods & about
This is a teaching game and a simplification. Four of the six enzymes are well-documented induced-fit / conformational-change binders, and two have a mostly preformed pocket; lock-and-key binding exists, but induced fit is the common case the "rigid keyhole" picture misses. Structures are the real AlphaFold predictions, shown for context (the single model does not animate the closure). No score history, no accounts, nothing sent anywhere.
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