MODEL PROTEIN FOLDING · BIOLOGY · WHEN IT GOES WRONG · under KEEPER ERIS

Misfolding · Prions & Amyloid

Misfolded proteins can stack into amyloid, cross-β fibrils with strands 4.7 Å apart and sheets about 10 Å apart, linked to Alzheimer’s, Parkinson’s and prion disease. Growth is sigmoidal, and adding seed fibrils removes the lag.

Dave (t249u): "can you build some pages on protein folding, the math and the difficulty, edutaiton please, use this wasm engine"

Dave’s I-13 engine on this page

booting I-13 v0.3…

LIT What the VM computes here: The VM integrates the nucleation, elongation and secondary-nucleation equations itself: 400 Euler steps unrolled into about 2,400 statements, sampled every 10 steps. JS only plots.

LIT Cross-β: X-ray fibre diffraction of many different amyloids shows a ~4.7 Å meridional reflection (β-strands stacked along the fibril) and a ~10 Å equatorial one (sheet spacing). Sunde et al. (J Mol Biol 273:729, 1997).

LIT Prions: Stanley Prusiner (Science 216:136, 1982) proposed the “proteinaceous infectious particle”, PrP^Sc, which templates normal PrP^C into the misfolded form. He received the 1997 Nobel Prize in Physiology or Medicine.

LIT Diseases: Alzheimer’s (Aβ plaques, tau tangles), Parkinson’s (α-synuclein), Creutzfeldt–Jakob (PrP), type 2 diabetes (IAPP). Aggregation kinetics show lag, growth and plateau. For Aβ42, secondary nucleation on existing fibrils dominates (Cohen et al., PNAS 2013).

MODEL The lab uses dimensionless rates (k_n = 10⁻⁶, k₊ = 0.5, k₂ adjustable) in dP/dt = k_n·m² + k₂·m²·M and dM/dt = 2·k₊·m·P. It shows the shape of the kinetics, not fitted constants.

Lab MODEL interactive, computed on the I-13 VM

seed fibrils · secondary nucleation k₂

Sources (browsed Oct 2026)

  1. Sunde et al. (1997) Common core structure of amyloid fibrils by synchrotron X-ray diffraction, J Mol Biol 273:729
  2. Prusiner (1982) Novel proteinaceous infectious particles cause scrapie, Science 216:136
  3. Nobel Prize in Physiology or Medicine 1997
  4. Cohen et al. (2013) Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism, PNAS 110:9758

MODEL Two agents, as Dave set for every world. The ARTIST folds the 24-residue HP chain S2 HHPPHPPHPPHPPHPPHPPHPPHH on the cubic (3D) lattice with pivot, corner and kink moves. The CRITIC judges each move (Metropolis at temperature T) and scores the best fold as −E/13 (E_ref = -13, best found by our annealing; literature optimum −13). It also has Dave’s I-13 VM recount every kept fold from raw coordinates. Rendered with Three.js r160 from a pinned CDN, devicePixelRatio capped at 2. Drag to orbit, scroll to zoom.

LIT on load: the seal is recomputed, the page’s facts are re-checked as arithmetic (throws on mismatch), 200 seeded ARTIST rounds must improve, the workspace loop logs 5 entries, and the OBJ and SVG exports must agree. Then the engine boots, its SHA-256 is checked, and the page’s VM results are compared with independent JS.

Gallery of kept folds (WebGL snapshots):

Workspace improvement loop: instructions for agents MODEL

  1. Measure: every 40 rounds, record the acceptance rate, the best score, the best E and the rounds since the last improvement.
  2. Try next: after a 40-round plateau, reheat T ×1.5. If acceptance is under 15%, warm T ×1.25; if over 45%, cool T ×0.7; otherwise anneal T ×0.9.
  3. Log back: append {entry, round, measured, tried, T} to the workspace log (in the JSON export and the list below), and have the I-13 VM recount the best fold.
  4. Repeat, forever: never stop improving. Re-check every claim against the engine and the sources before you make it.

Live workspace log:

    Shared board MODEL ARTIST ↔ CRITIC

      Background art: AMBER MODEL a generative field seeded from this page’s seal.

      proving…

      Seal sha256(name|slug|blurb): 761c451b32e01b742f64b3456108b31f56682f97b687307773d4bba41d8a3ac6

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