Mechanical Activation Drastically Accelerates Amide Bond Hydrolysis, Matching Enzyme Activity
Why this work is in the frame
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Bibliographic record
Abstract
Abstract Amide bonds, which include peptide bonds connecting amino acids in proteins and polypeptides, give proteins and synthetic polyamides their enormous strength. Although proteins and polyamides sustain mechanical force in nature and technology, how forces affect amide and peptide bond stability is still unknown. Using single‐molecule force spectroscopy, we discover that forces of only a few hundred pN accelerate amide hydrolysis 10 9 ‐fold, an acceleration hitherto only known from proteolytic enzymes. The drastic acceleration at low force precedes a moderate additional acceleration at nN forces. Quantum mechanochemical ab initio calculations explain these experimental results mechanistically and kinetically. Our findings reveal that, in contrast to previous belief, amide stability is strongly force dependent. These calculations provide a fundamental understanding of the role of mechanical activation in amide hydrolysis and point the way to potential applications from the recycling of macromolecular waste to the design of bioengineered proteolytic enzymes.
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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 | 0.000 |
| 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) | 0.002 | 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