Development of gel and fluorescence based assays to monitor DNA cleavage, binding, and inhibition by the human cytomegalovirus terminase UL89-C
Bibliographic record
Abstract
The terminase enzyme of the Human Cytomegalovirus (HCMV) is responsible for the packaging and cleaving of concatameric viral DNA during viral replication. Due to its vital role in the viral life cycle, the terminase enzyme has the potential to become a strong candidate for anti-viral treatments. Furthermore, there is no mammalian equivalent; therefore, drugs targeted to terminase-like proteins should be safe and highly selective.In order to study and screen potential inhibitors to the terminase enzyme, we developed gel-based DNA cleavage assays with a resolution of a single nucleotide, which allowed us to detect the precise cleavage of DNA substrates via the C-terminal nuclease domain of the UL89 terminase subunit (UL89-C). We then utilized these assays to screen compound libraries provided by various collaborators. Furthermore, we then attempted to develop a DNA binding assay to characterize the DNA binding ability of UL89-C, and its T4 bacteriophage homolog gp17, using fluorescence anisotropy. Thus, our results have not only important implications with regards to drug discovery efforts, but also shed light on the mechanisms of DNA binding and cleavage, drug action, and potential drug resistance. Furthermore, due to the conserved nature of the terminase nuclease, these active site inhibitors may have broad-spectrum anti-herpetic properties.
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How this classification was reachedexpand
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".