Proteome mining of Yersinia Enterocolitica for drug targets and computational inhibitor identification with ADMET, anti-inflammation potential and formulation characteristics
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Yersinia enterocolitica infection can manifest as self-limiting gastroenteritis and may lead to more severe conditions, such as mesenteric lymphadenitis, reactive arthritis, or rare systemic infections. Fluoroquinolones and third-generation cephalosporins are the most effective treatment options but tetracyclines and co-trimoxazole effectiveness may vary based on resistance patterns. To explore new therapeutic options in case of antibiotic resistance, we initially mined drug targets from the Yersinia enterocolitica proteome using a subtractive proteomics approach. Subsequently, we repurposed FDA approved & Traditional Chinese Medicinal (TCM) compounds against its cell wall synthesis mechanism by targeting DD-transpeptidase. DrugRep screening prioritized FDA-approved hits (Digitoxin, Irinotecan, Acetyldigitoxin; ≤ -9.4 kcal/mol) and TCM hits (Vaccarin, Narirutin, Hinokiflavone; ≤ -9.5 kcal/mol). Machine learning-based validation identified Hinokiflavone and Acetyldigitoxin as most potent binders. Molecular dynamics simulations (100 ns) revealed RMSD values < 1 nm for all complexes, indicating stable binding. ADMET profiling predicted all compounds as non-allergenic and TCM compounds having poor absorption. SBE-β-cyclodextrin coupling with FormulationAI showed improved compound solubility and oral bioavailability. InflamNat predicted strong anti-inflammatory potential for Hinokiflavone, highlighting its dual role in antibacterial and host-directed immunomodulatory activity. These computational insights mark an initial step in drug discovery, prompting comprehensive testing of prioritized compounds against Yersinia enterocolitica.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 it