Single Molecules of Highly Purified Bacterial Alkaline Phosphatase Have Identical Activity
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Bibliographic record
Abstract
The central paradigm of chemistry is that molecular structure determines molecular function. Details of this paradigm can be tested with single-molecule enzymology, where the activity of individual molecules is studied. In all cases reported thus far, there is a large molecule-to-molecule heterogeneity in activity and activation energy. This heterogeneity must arise from differences in structure. Replicate incubations on the same molecule yield consistent results; the structural heterogeneity must be stable over the time period of the experiment, which can extend over several hours. In this paper, we demonstrate that highly purified molecules of bacterial alkaline phosphatase generate identical activity; structurally identical molecules behave identically. In contrast, the glycosylated mammalian enzyme demonstrates a complex isoelectric focusing pattern and has a dramatic molecule-to-molecule variation in activity and activation energy. Glycosylation affects both the kinetics and energetics of this enzymatically catalyzed reaction.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 it