Residue patterning in helix interiorsThis paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process.
Bibliographic record
Abstract
The alpha-helix remains a focus of research because of its importance to protein folding and structure. Nevertheless, despite numerous empirical, computational, and theoretical studies, the fundamental structural properties governing their formation and stability are still unclear. We have examined the statistical occurrence of polar and apolar residue patterning in helical interiors in a large, non-redundant dataset, and compared these patterns with those found in other structural environments. While the familiar amphipathic distributions for both polar and apolar residues are evident, our analysis also finds significant differences between these distributions. Non-amphipathic signals can also be discerned within both distributions. Most interestingly, among various positional patterning, an analysis of immediate (i,i + 1) helical neighbours found: (i) clear neighbouring preferences, with high (low) occurrences of hydrophobics (hydrophilics) next to Gly, Pro, and short polar residues; (ii) high negative (positive) correlation between residue helical propensities and the degree of neighbouring hydrophobicity (hydrophilicity); and (iii) a preferred ordering among neighbours, implying an inherent helix directionality. Because (i,i + 1) helical pairs have limited side chain - side chain interactions, thermodynamic considerations cannot readily explain these observations, nor can evolutionary pressures that enhance tertiary interactions via amphipathicity, as this particular spacing does not segregate residues onto either the same or opposing helical faces. We suggest that the mechanism of helix formation may be partly responsible for these observations. In particular, the high negative correlation between residue helical propensities and neighbouring hydrophobicity suggests that hydrophobicity may play a more important role in helix formation than currently recognized.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.004 |
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".