Rationally Designed Allosteric Variants of Hammerhead Ribozymes Responsive to the HIV-1 Tat Protein
Bibliographic record
Abstract
Hammerhead ribozymes that are subject to allosteric control by small molecule and oligonucleotide effectors have been reported recently. Rational design has been an effective strategy for the creation of these ribozymes, which incorporate structurally interdependent hammerhead motifs and effector-binding sequences. In this paper we report the rational design of the first protein-responsive allosteric ribozymes that are regulated by the HIV-1 Tat. The TAR-Tat interaction of HIV-1 has the interesting feature that both Tat and arginine are able to bind to and bring about comparable conformational changes in the TAR loop. Here we describe the construction of two classes of TAR-modified hammerhead ribozymes and their response to Tat protein and to its derivatives. Instances of both allosteric activation and inhibition were found. Interestingly, the activation response was stimulated by both Tat and argininamide while the inhibitory response was stimulated by Tat and by its derivative peptide, ADP1, but not by argininamide. Overall, the extent of allosteric response in our ribozymes was modest relative to those reported for ribozymes with small molecule effectors. Future work utilizing combinatorial approaches along with elements of rational design should reveal the means by which highly efficient, protein-mediated allostery of ribozymes may be achieved.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.001 | 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".