Structure-based chemical probe development of the PWWP domain containing proteins
Bibliographic record
Abstract
The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. PWWP domain-containing proteins are often involved in chromatin-associated biological processes, such as transcriptional regulation and DNA repair, and recent studies have shown that the PWWP domain specifies chromatin localization. Mutations in the PWWP domain, a 100-150 amino acid motif, have been linked to various human diseases, emphasizing its importance. Structural studies reveal that PWWP domains possess a conserved aromatic cage for histone methyl-lysine recognition, and synergistically bind both histone and DNA, which contributes to their nucleosome-binding ability and chromatin localization. Furthermore, the PWWP domain often cooperates with other histone and DNA 'reader' or 'modifier' domains to evoke crosstalk between various epigenetic marks. In recent years, we systematically studied the human PWWP domain proteins in terms of histone and DNA binding abilities and the development of specific chemical probes. The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. PWWP domain-containing proteins are often involved in chromatin-associated biological processes, such as transcriptional regulation and DNA repair, and recent studies have shown that the PWWP domain specifies chromatin localization. Mutations in the PWWP domain, a 100-150 amino acid motif, have been linked to various human diseases, emphasizing its importance. Structural studies reveal that PWWP domains possess a conserved aromatic cage for histone methyl-lysine recognition, and synergistically bind both histone and DNA, which contributes to their nucleosome-binding ability and chromatin localization. Furthermore, the PWWP domain often cooperates with other histone and DNA 'reader' or 'modifier' domains to evoke crosstalk between various epigenetic marks. In recent years, we systematically studied the human PWWP domain proteins in terms of histone and DNA binding abilities and the development of specific chemical probes.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 |
| Open science | 0.001 | 0.000 |
| 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".