Oxidative Protein Labeling with Analysis by Mass Spectrometry for the Study of Structure, Folding, and Dynamics
Bibliographic record
Abstract
SIGNIFICANCE: Analytical approaches that can provide insights into the mechanistic processes underlying protein folding and dynamics are few since the target analytes-high-energy structural intermediates-are short lived and often difficult to distinguish from coexisting structures. Folding "intermediates" can be populated at equilibrium using weakly denaturing solvents, but it is not clear that these species are identical to those that are transiently populated during folding under "native" conditions. Oxidative labeling with mass spectrometric analysis is a powerful alternative for structural characterization of proteins and transient protein species based on solvent exposure at specific sites. RECENT ADVANCES: Oxidative labeling is increasingly used with exceedingly short (μs) labeling pulses, both to minimize the occurrence of artifactual structural changes due to the incorporation of label and to detect short-lived species. The recent introduction of facile photolytic approaches for producing reactive oxygen species is an important technological advance that will enable more widespread adoption of the technique. CRITICAL ISSUES: The most common critique of oxidative labeling data is that even with brief labeling pulses, covalent modification of the protein may cause significant artifactual structural changes. FUTURE DIRECTIONS: While the oxidative labeling with the analysis by mass spectrometry is mature enough that most basic methodological issues have been addressed, a complete systematic understanding of side chain reactivity in the context of intact proteins is an avenue for future work. Specifically, there remain issues around the impact of primary sequence and side chain interactions on the reactivity of "solvent-exposed" residues. Due to its analytical power, wide range of applications, and relative ease of implementation, oxidative labeling is an increasingly important technique in the bioanalytical toolbox.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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 source (direct Gemma or distilled Codex), 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".