Label-Free Assay for Thermodynamic Analysis of Protein−Ligand Interactions: A Multivariate Strategy for Allosteric Ligand Screening
Bibliographic record
Abstract
The binding of allosteric ligands to protein can induce changes to the holoprotein conformation, stability, and activity that have an impact on unfolding dynamics. Herein we report a label-free strategy for determining the dissociation constant of protein-ligand interactions over a wide dynamic range (>10(4), Kd from nano- to millimolar) using capillary electrophoresis that overcomes the constraints of an ideal two-state protein unfolding model. Multivariate analysis of thermodynamic parameters associated with holoprotein unfolding and ligand binding is demonstrated for the classification of cyclic nucleotide analogues that function as allosteric modulators of regulatory proteins, such as the exchange protein directly activated by cAMP (EPAC).
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".