Single-molecule assays for investigating protein misfolding and aggregation
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Bibliographic record
Abstract
Protein misfolding and aggregation are relevant to many fields. Recently, their investigation has experienced a revival as a central topic in the research of numerous human diseases, including Parkinson's and Alzheimer's. Much has been learned from ensemble biochemical approaches, but the inherently heterogeneous nature of the underlying processes has obscured many important details. Single-molecule techniques offer unique capabilities to study heterogeneous systems, while providing high temporal and structural resolution to characterize them. In this Perspective, we give an overview of the single-molecule assays that have been applied to protein misfolding and aggregation, which are mainly based on fluorescence and force spectroscopy. We describe some of the technical challenges involved in studying aggregation at the single-molecule level and discuss what has been learned about aggregation mechanisms from the different approaches.
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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) | 0.000 | 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