Molecular Calipers for Highly Precise and Accurate Measurements of Single-Protein Mechanics
Bibliographic record
Abstract
Single-molecule atomic force spectroscopy (AFM) has evolved into a powerful technique toward elucidating conformational changes in proteins when exposed to applied force. AFM technologies that are currently available allow for precise measurements of proteins length changes during conformational transitions. However, because of systematic errors in piezo calibration as well as errors originating from fitting experimental data using a worm-like chain model of polymer elasticity, high-precision measurements of length changes do not necessarily translate into highly accurate measurements of length changes, resulting in uncertainty in obtaining structural information about protein conformational changes. Actually achieving highly precise and accurate force spectroscopy measurements remains a challenge. Here, we report a protein caliper method that eliminates systematic errors that occur during single-protein force spectroscopy measurements, and thus achieves highly precise and accurate length change measurements in protein mechanics studies. To do this, a series of loop elongation variants of the small protein GB1, which differ by 2, 5, 10, 15, and 24 amino acid residues, were engineered. Differential measurements of amino acid residue length obtained from different AFM setups result in a precise measure of the length of a single amino acid residue, which varies within different AFM setups because of systematic error between individual AFM piezoelectric calibrations. The measured length of a single amino acid residue from a given AFM setup is then used as a caliper for the given setup to eliminate systematic error, leading to highly accurate and precise measurements of the number of amino acid residues that are involved in a conformation change of a polypeptide chain. We further developed a more precise, robust, and model-free method to determine the apparent size of single amino acid residues and conformational changes of proteins. This method improves the accuracy of single protein force spectroscopy measurements, providing an accurate means of measuring force-induced protein conformational changes.
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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".