Mutual Information in Protein Multiple Sequence Alignments Reveals Two Classes of Coevolving Positions
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Bibliographic record
Abstract
Information theory was used to identify nonconserved coevolving positions in multiple sequence alignments from a variety of protein families. Coevolving positions in these alignments fall into two general categories. One set is composed of positions that coevolve with only one or two other positions. These positions often display direct amino acid side-chain interactions with their coevolving partner. The other set comprises positions that coevolve with many others and are frequently located in regions critical for protein function, such as active sites and surfaces involved in intermolecular interactions and recognition. We find that coevolving positions are more likely to change protein function when mutated than are positions showing little coevolution. These results imply that information theory may be applied generally to find coevolving, nonconserved positions that are part of functional sites in uncharacterized protein families. We propose that these coevolving positions compose an important subset of the positions in an alignment, and may be as important to the structure and function of the protein family as are highly conserved positions.
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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 | 0.000 | 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) | 0.000 | 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 it