Polymer principles of protein calorimetric two‐state cooperativity
Bibliographic record
Abstract
The experimental calorimetric two-state criterion requires the van't Hoff enthalpy ∆HvH around the folding/unfolding transition midpoint to be equal or very close to the calorimetric enthalpy ∆H cal of the entire transition.We use an analytical model with experimental parameters from chymotrypsin inhibitor 2 to elucidate the relationship among several different van't Hoff enthalpies used in calorimetric analyses.Under reasonable assumptions, the implications of these ∆HvH's being approximately equal to ∆H cal are equivalent: Enthalpic variations among denatured conformations in real proteins are much narrower than some previous lattice-model estimates, suggesting that the energy landscape theory "folding to glass transition temperature ratio" T f /Tg may exceed 6.0 for real calorimetrically two-state proteins.Several popular three-dimensional lattice protein models, with different numbers of residue types in their alphabets, are found to fall short of the high experimental standard for being calorimetrically two-state.Some models postulate a multiple-conformation native state with substantial pre-denaturational energetic fluctuations well below the unfolding transition temperature and/or predict a significant post-denaturational continuous conformational expansion of the denatured ensemble at temperatures well above the transition point.These scenarios either disagree with experiments on protein size and dynamics, or are inconsistent with conventional interpretation of calorimetric data.However, when empirical linear baseline subtractions are employed, the resulting ∆HvH/∆H cal 's for some models can be increased to values closer to unity; and baseline subtractions are found to correspond roughly to an operational definition of native-state conformational diversity.These results necessitate a re-assessment of theoretical models and experimental interpretations.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".