Structural Basis for Inhibitor Potency and Selectivity of <i>Plasmodium falciparum</i> Phosphatidylinositol 4-Kinase Inhibitors
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
Plasmodium falciparum phosphatidylinositol 4-kinase ( Pf PI4K) has emerged as a promising new drug target for novel antimalarial therapeutics. In the absence of a reliable high-resolution three-dimensional structure, a homology model of Pf PI4K was built as a tool for structure-based drug design. This homology model has been validated against three distinct chemical series of potent inhibitors using docking and energy minimizations to elucidate the interactions crucial for PI4K inhibition and potent antiplasmodium activity. Despite its potential as an antimalarial target, the similarity between Pf PI4K and structurally related human kinases poses a risk for human off-target kinase activity and associated toxicity. Comparative docking between Pf PI4K and human phosphoinositide kinases (PIKs) presents compelling evidence for the origins of selectivity. This in-depth analysis of the Pf PI4K homology model, the binding modes of the inhibitors, and the interactions responsible for selectivity over human kinases provides a powerful template for future optimization of Plasmodium PI4K inhibitors.
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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 | 0.001 |
| 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