Optimal Attachment Position and Linker Length Promote Native‐like Character of Cavitand‐Based Template‐Assembled Synthetic Proteins (TASPs)
Bibliographic record
Abstract
We have designed, synthesised and characterised a series of template-assembled de novo four-helix bundles, each differing in the linker length between the template and the peptides. The helix is based on an earlier peptide sequence: EELLKKLEELLKKLG (first-generation sequence), which was designed to link the hydrophilic/hydrophobic interface of the helices. Increasing or decreasing the linker length by one glycine residue had a significant effect on the structure and properties of the template-assembled synthetic proteins (TASPs). Here, the effect of the linker length is further probed by linking the peptides closer to the hydrophobic face by using the second-generation sequence, AEELLKKLEELLKKG, in an effort to improve the packing between the helices and to better understand the helical bundles. The peptides were synthesised with 0-4 Gly linker residues and linked onto a cavitand template. The proteins were found to be alpha-helical, stable to guanidine hydrochloride (GuHCl) and to unfold cooperatively. However, their stabilities toward GuHCl, propensity to self-aggregate and structural specificity differed. The two-glycine variant of the second-generation series demonstrated the highest stability and most native-like character of all the mononeric TASPs in both the first- and second-generation series. The structural specificity of this two glycine variant is comparable to that of other known native-like de novo proteins. Molecular dynamics simulations showed that the two-glycine variant contains helices that are tilted with respect to the cavitand template and may account for its unique properties.
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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 | 0.001 | 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".