R3Design: deep tertiary structure-based RNA sequence design and beyond
Bibliographic record
Abstract
The rational design of Ribonucleic acid (RNA) molecules is crucial for advancing therapeutic applications, synthetic biology, and understanding the fundamental principles of life. Traditional RNA design methods have predominantly focused on secondary structure-based sequence design, often neglecting the intricate and essential tertiary interactions. We introduce R3Design, a tertiary structure-based RNA sequence design method that shifts the paradigm to prioritize tertiary structure in the RNA sequence design. R3Design significantly enhances sequence design on native RNA backbones, achieving high sequence recovery and Macro-F1 score, and outperforming traditional secondary structure-based approaches by substantial margins. We demonstrate that R3Design can design RNA sequences that fold into the desired tertiary structures by validating these predictions using advanced structure prediction models. This method, which is available through standalone software, provides a comprehensive toolkit for designing, folding, and evaluating RNA at the tertiary level. Our findings demonstrate R3Design's superior capability in designing RNA sequences, which achieves around $44\%$ in terms of both recovery score and Macro-F1 score in multiple datasets. This not only denotes the accuracy and fairness of the model but also underscores its potential to drive forward the development of innovative RNA-based therapeutics and to deepen our understanding of RNA biology.
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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 | 0.000 | 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 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".