DisorderDuty
When AlphaFold draws part of a protein in pale, low-confidence colour, it is easy to read it as “wrong” or “unfinished”. Usually it means the opposite kind of thing: that stretch is intrinsically disordered — genuinely floppy — and that floppiness is often exactly how it works. Some pale stretches are something else again: pieces the cell cuts off before the protein is finished. Tag each low-pLDDT stretch Broken, Working or Cut off, then see the live UniProt annotation prove what it does. Everything runs locally; nothing about you is collected.
This is the tool. Your call is scored against the region’s live UniProt functional annotations, fetched in your browser. The regions are listed in full 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 full region guide below still works.
How to play. Press Start. A pale, low-pLDDT stretch is highlighted — decide Broken, Working or Cut off (buttons or keys 1/B, 2/W, 3/C). The stretch’s name appears after your call, because a name like “signal peptide” would give the answer away. The live UniProt annotation is revealed and your call is scored. Press Enter or Next to continue.
Why the floppy parts are working parts
The working regions you tagged are flexible in the living cell too, and that flexibility is part of the job. p53's N-terminal stretch binds MDM2 and other partners, folding differently onto each one; its C-terminal end carries chemical marks that tune its activity, and histone H3's tail is marked and unmarked by enzymes that change how tightly DNA is packed. The cut-off pieces are different: signal peptides and propeptides guide a protein's making and are then removed, so the model has no fixed place to put them. Neither kind is a drawing error.
Low confidence is not the same as wrong
AlphaFold’s pLDDT is a per-residue confidence. Very low pLDDT often flags a region that is intrinsically disordered — it has no single fixed shape because it does not need one. Those regions do real work: they wrap onto partners, carry chemical marks, and fold up only when they touch the right surface. Other pale stretches are signal peptides and propeptides: they guide a protein’s making and are then removed, so the model has no fixed place to put them. Reading “pale” as “error” is a common misreading, and this game trains the opposite reflex: pale usually means flexible and working, or cut away.
The regions
Answer key — open it after you play
| Protein | Region | What it does |
|---|---|---|
| p53 TP53 · P04637 | N-terminal transactivation domain (TAD) (1–61) | Disordered, yet the business end — binds MDM2 and the transcription machinery. |
| p53 TP53 · P04637 | C-terminal regulatory domain (363–393) | Disordered and heavily modified; tunes DNA binding, a hub of post-translational marks. |
| Histone H3.1 H3C1 · P68431 | N-terminal tail (1–40) | The disordered canvas of the histone code — its modifications switch genes on and off. |
| Serum albumin ALB · P02768 | Signal peptide (1–18) + propeptide (19–24) (1–24) | Cut off: they send albumin out of the cell, then are removed. The finished protein starts after them. |
| Insulin INS · P01308 | C-peptide (a propeptide) (57–87) | Cut off: it links the two chains while proinsulin folds, then is cut out and released alongside insulin. |
| Lysozyme C LYZ · P61626 | Signal peptide (1–18) | Cut off: it gets lysozyme exported, then is removed from the finished enzyme. |
Methods & about
This is a teaching game, honest about being a simplification. In this deck no region is “Broken”. That is the lesson: a low-confidence stretch is usually floppy and doing a job, or a piece the cell cuts away; it is rarely a drawing error. Rarely is not never: the model can also be unsure about a part that is actually ordered, for example when it has few related sequences to learn from. Every stretch here reads low in the AlphaFold Database (checked at every build), and the reveal fetches its live UniProt features (regions, binding sites, modified residues, motifs, or the signal peptide / propeptide) as evidence. Structures are the real AlphaFold predictions; annotations are live from UniProt. The game keeps no score history, uses no accounts, and sends nothing anywhere.
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