Most yeast SH3 domains bind peptide targets with high intrinsic specificity
Bibliographic record
Abstract
A need exists to develop bioinformatics for predicting differences in protein function, especially for members of a domain family who share a common fold, yet are found in a diverse array of proteins. Many domain families have been conserved over large evolutionary spans and representative genomic data during these periods are now available. This allows a simple method for grouping domain sequences to reveal common and unique/specific binding residues. As such, we hypothesize that sequence alignment analysis of the yeast SH3 domain family across ancestral species in the fungal kingdom can determine whether each member encodes specific information to bind unique peptide targets. With this approach, we identify important specific residues for a given domain as those that show little conservation within an alignment of yeast domain family members (paralogs) but are conserved in an alignment of its direct relatives (orthologs). We find most of the yeast SH3 domain family members have maintained unique amino acid conservation patterns that suggest they bind peptide targets with high intrinsic specificity through varying degrees of non-canonical recognition. For a minority of domains, we predict a less diverse binding surface, likely requiring additional factors to bind targets specifically. We observe that our predictions are consistent with high throughput binding data, which suggests our approach can probe intrinsic binding specificity in any other interaction domain family that is maintained during evolution.
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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 | 0.000 | 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) | 0.002 | 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".