Simple and versatile restraints for the accurate modeling of α‐helical coiled‐coil structures of multiple strandedness, orientation and composition
Bibliographic record
Abstract
We present a minimalist approach for the modeling of the three-dimensional structure of multistranded alpha-helical coiled coils. The approach is based on empirical principles introduced by F. H. C. Crick (F. H. C. Crick, Acta Crystallogr, 1953, Vol. 6, pp. 689-697). Crick hypothesized that keeping the distance between the residues at the interacting interface of alpha-helices constant would lead to supercoiling or the formation of a coiled coil through the knobs-into-holes mode of packing. We have implemented the latter hypothesis in a simulating annealing protocol in the simple form of interhelical distance restraints (two per heptad) between Calpha at the interfacial positions and. To demonstrate the authenticity of Crick's hypothesis and the precision and accuracy of our approach, we have modeled the crystal structures of six synthetic coiled coils in dimeric, trimeric, and tetrameric states. The mean root mean square deviations (RMSDs) between the backbone atoms of the ensemble of structures calculated and those of the corresponding geometric averages is always below 0.76 A, indicating that our protocol has an excellent degree of convergence and precision. The RMSDs between the backbone atoms of each of the six geometric average structures and the backbone of the corresponding crystal structures all range between 0.43 and 0.95 A, indicative of excellent accuracy and proving the authenticity of Crick's hypothesis. Moreover, without specifying any dihedral angles, we found that in 81% of the occurrences, the most populated conformer of the side chains at positions and in the ensembles calculated were identical to those observed in the crystal structures. This shows that our simple approach, which is the simplest reported so far, can generate accurate results for the backbone and side chains. Finally, as a test case for a wider application of our approach in the field of structural proteomics, we describe the successful modeling of the overall structure of SNARE and the organization of its interfacial ionic layer known to play an important functional role.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".