Plasmodium falciparum Neutral Aminopeptidases: Development of Novel Anti-Malarials by Understanding Enzyme Structure
Bibliographic record
Abstract
Malaria is the world's most prevalent human parasitic disease. Because of the rapid spread of drug resistance in the parasite, there is an urgent need to identify new diverse drug targets. Within the complex intra-erythrocytic life-cycle of the parasite, the activity of two neutral metalloaminopeptidases is essential to the parasite's growth and development. Inhibition of the combined activity of the m1 alanyl aminopeptidase and the m17 leucyl aminopeptidase prevents the growth of Plasmodium falciparum parasites in culture, and protects mice from infection with the rodent malaria species P. c. chabaudi, providing strong support for considering them as targets for which a new class of anti-malarial drugs can be developed. The high-resolution X-ray crystal structures of both enzymes have been elucidated and provide valuable structural and mechanistic detail to facilitate the development of compounds in future rational drug-design programs.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.011 | 0.012 |
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".