Pressure-Dependent Properties of Elementary Hydrophobic Interactions: Ramifications for Activation Properties of Protein Folding
Bibliographic record
Abstract
Hydration effects on a pair of methane molecules are investigated by extensive constant-pressure (NPT) sampling using the TIP4P model of water under 1, 1000, 2000, and 3000 atm. The volume distributions of pure water and of methanes plus water are determined directly as functions of methane-methane distance ξ. The corresponding excess isothermal and adiabatic compressibilities are estimated from the pressure-dependent methane excess volume. The dependence of excess volume on ξ is oscillatory for small ξ. The maxima of excess volume and compressibility are seen near the desolvation barrier (db) of the potential of mean force (PMF). These features may be understood by the development, near the db, of a void volume encased by a molecular (Connolly) surface defined using a water-sized probe. These db properties for two methanes are consistent with well-corroborated experimental observations of positive activation volumes for protein folding and some experiments suggesting a slightly higher compressibility for the folding transition state than the unfolded state. At high pressures, the volumes at the PMF solvent-separated minimum and the contact-minimum configurations are both smaller than the volume at large ξ. This trend provides a rationalization for the compactness of pressure-denatured states of proteins. Taking the packing densities of pure nonpolar phases into consideration, our simulation results suggest that whether the activation volume of unfolding is positive or negative hinges on the packing compactness of the protein core. Volume change can be but is not necessarily monotonic along the folding pathway.
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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".