{"record":{"author":{"account_ref":null,"orcid":null},"builds_on":[],"content_schema":"pubphys.content.revision/1","content_sha256":"e888351e54b6b0729791b33239a1339c5dbe73423d78262cb66495a7179e9512","created":"2026-10-15T23:43:22Z","files":[],"origin":{"assisted_by":["ai:gpt-5.5"],"kind":"seed"},"parents":["af6cb084a5ea68e61c06cca518806c6355e88e46df12158859b365fd3b000d37","ce59fb6cd812fc05906d0c60a71c75ea22bc686bcf38e7c3ef7010834d98ee7b"],"salt":"19ba3405ee7a1acb787d013150cb43d9de703bfe6dcd56bf5a643f1501c9711e","schema":"pubphys.record/2","site":"pubphys.com","target":null,"type":"revision"},"content":{"answer_type":"mechanism","assisted_by":["ai:gpt-5.5"],"external_id":"bio.protein-folding.amyloid-nucleation","kind":"well-posed","literature_status":"open","n":"2","parents":[],"plain":"Some proteins stack into long fibers called amyloids, and the surface of an existing fiber speeds up the birth of new ones, which drives the self-amplifying aggregation seen in neurodegenerative disease. How the fiber surface does this, molecule by molecule, is unknown.","posed_since":"2013","precise":"For A-beta42 at neutral pH and $\\alpha$-synuclein at mildly acidic pH (about 5 to 6) in vitro, aggregation kinetics fit a master equation in which secondary nucleation on fibril surfaces, at rate $k_{2}$ m^$n_{2}$ M (m = monomer concentration, M = fibril mass concentration), dominates the formation of new aggregates. Determine the microscopic steps (adsorption, conformational conversion on the surface, detachment) and compute $k_{2}$ and the reaction order $n_{2}$ from a molecular model, matching measured values within a factor of 3.","problem_ref":"af6cb084a5ea68e61c06cca518806c6355e88e46df12158859b365fd3b000d37","references":"","settled_by":"A molecular simulation or structural-kinetic model that predicts $k_{2}$ and $n_{2}$ and their dependence on sequence mutations, confirmed by bulk kinetics and single-fibril imaging.","status_note":"Kinetic analysis established secondary nucleation as the dominant source of new A-beta42 aggregates in 2013; its molecular steps remain unresolved.","title":"Molecular mechanism of secondary nucleation on amyloid fibrils","topic_ref":null},"attested":{"attestation":{"batch":null,"client_id":null,"id_token_sha256":null,"kind":"platform"},"record_hash":"fdfa8c626608512c588c37013c91f9be3ac22bd76f0cee542686c67f0e767d5e","schema":"pubphys.attested/1"},"envelope":{"attested_hash":"19a6d25c3bf48d2d5530f78259d9a32c72751fc498dab830076d85c9031fac52","platform_signature":{"key_id":"c6afc19b31429869751f06879c75cd64ea92654423d15b44be775bf1310a60da","sig":"y3Au2qbpUEiV7IvOELEjwoeBcZbjSkkqCaDRnQH_0hgyfGzGSOFYThUEAOd6Y7Y3C60i_GSa54jeSJQ7oPKyCA"},"schema":"pubphys.envelope/1"},"record_hash":"fdfa8c626608512c588c37013c91f9be3ac22bd76f0cee542686c67f0e767d5e","leaf_index":2620}