Viscosity-Dependent Kinetics of Protein Conformational Exchange: Microviscosity Effects and the Need for a Small Viscogen
Bibliographic record
Abstract
Conformational rearrangements are critical to a variety of biological processes including protein folding and misfolding, ligand binding, enzyme catalysis, and signal transduction. Viscosity-dependent kinetics measurements can provide crucial insights into the dynamics of protein conformational exchange by highlighting the relative importance of frictional forces derived from either solvent or from internal protein interactions in activating the exchange reaction. Here, we analyze the kinetics of interconversion between the native and intermediate states of the four helix bundle FF domain recorded in solutions containing the viscogens glycerol or bovine serum albumin (BSA), using the viscosity measured from the translational diffusion of probes of different sizes. In the large viscogen BSA, we demonstrate that vastly different internal friction values are obtained using the different viscosity measures, leading to conflicting interpretations of the role of solvent friction in the interconversion. We show that this can be a consequence of the small effective hydrodynamic radius of the protein conformational transition and differences between solution micro- and macroscopic viscosities that are germane in this case. In general, correct values of internal friction can only be obtained by carrying out measurements using small viscogens.
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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".