{"schema":"pubphys.bundle/1","record":{"author":{"account_ref":null,"orcid":null},"builds_on":[],"content_schema":"pubphys.content.revision/1","content_sha256":"6edf0bba6fce695fb6efeb1f829ce390caabdc6389852dd65b2477d70f815f9e","created":"2026-10-03T07:17:57Z","files":[],"origin":{"assisted_by":[],"kind":"seed"},"parents":["5475cf5dc5b1a72283d26dc95dc6e00d7ea4e00096a7c6492e409a1816eeb011"],"salt":"527c3e750f679cd8d93e63b58a072702a2923fd7641cfdb41b43dc08e37a6257","schema":"pubphys.record/2","site":"pubphys.com","target":null,"type":"revision"},"content":{"answer_type":"mechanism","assisted_by":[],"external_id":"bio.protein-folding.speed-limit","kind":"well-posed","literature_status":"partially-resolved","n":"1","parents":[],"plain":"The fastest proteins fold in about a microsecond, and theory and experiment suggest a floor of roughly N/100 microseconds for a chain of N amino acids. The question is which physical process sets this floor: the chain moving through water, or friction inside the chain itself.","posed_since":"2004","precise":"For ultrafast folders (villin headpiece, WW domains; folding times $\\sim 1 \\text{ to } 10\\ \\mathrm{microseconds}$), determine the prefactor $k_0$ in the Kramers rate $k = k_0 \\exp(-dG/k_B T)$, with the empirical estimate $\\tau_{\\min} \\sim N/100\\ \\mathrm{microseconds}$ for $N$ residues (Kubelka, Hofrichter and Eaton, 2004), and separate solvent from internal friction through the viscosity dependence $\\tau = a\\eta + b$ at fixed stability ($\\eta = \\text{solvent viscosity}$). An answer gives $k_0$ and the internal-friction term $b$ with their molecular origin (backbone dihedral barriers, side-chain contacts) and reproduces measured $\\eta$-dependences.","problem_ref":null,"references":"","settled_by":"Viscosity-dependent single-molecule transition-path and folding-time measurements on ultrafast folders matched by all-atom or coarse-grained simulations that identify the friction source.","status_note":"Single-molecule measurements since 2012 bound transition-path times at microseconds; the molecular origin of internal friction is still disputed as of 2026, to this survey's knowledge.","title":"What sets the folding speed limit and internal 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