Single molecule force spectroscopy reveals engineered metal chelation is a general approach to enhance mechanical stability of proteins
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Bibliographic record
Abstract
Significant mechanical stability is an essential feature shared by many elastomeric proteins, which function as molecular springs in a wide variety of biological machinery and biomaterials of superb mechanical properties. Despite the progress in understanding molecular determinants of mechanical stability, it remains challenging to rationally enhance the mechanical stability of proteins. Using single molecule force spectroscopy and protein engineering techniques, we demonstrate that engineered bi-histidine metal chelation can enhance the mechanical stability of proteins significantly and reversibly. Based on simple thermodynamic cycle analysis, we engineered a bi-histidine metal chelation site into various locations of the small protein, GB1, to achieve preferential stabilization of the native state over the mechanical unfolding transition state of GB1 through the binding of metal ions. Our results demonstrate that the metal chelation can enhance the mechanical stability of GB1 by as much as 100 pN. Since bi-histidine metal chelation sites can be easily implemented, engineered metal chelation provides a general methodology to enhance the mechanical stability of a wide variety of proteins. This general approach in protein mechanics will enable the rational tuning of the mechanical stability of proteins. It will not only open new avenues toward engineering proteins of tailored nanomechanical properties, but also provide new approaches to systematically map the mechanical unfolding pathway of proteins.
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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 | 0.001 |
| 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 it