| --- |
| tags: |
| - Biology |
| - RNA Design |
| - Inverse Folding |
| - Geometric Deep Learning |
| license: agpl-3.0 |
| library_name: ofoldx |
| pipeline_tag: other |
| --- |
| |
| # gRNAde |
|
|
| Geometric RNA inverse folding with a multi-conformation GVP encoder and |
| autoregressive nucleotide decoder. |
|
|
| ## Disclaimer |
|
|
| This is an unofficial OFoldX implementation of |
| [gRNAde](https://github.com/chaitjo/geometric-rna-design). The upstream authors |
| did not write, review, or endorse this implementation or model card. |
|
|
| ## Model Details |
|
|
| gRNAde predicts RNA identities from one-dimensional sequence order, explicit |
| secondary-structure base pairs, and optional three-dimensional backbone |
| geometry. `GrnadeProcessor` lowers one canonical RNA chain or aligned |
| conformations to P, C4', and base-nitrogen features, sequence, base-pair, and |
| spatial edges, native identities, and a design mask. The secondary structure is |
| a dot-bracket string read by MultiMolecule; further bracket types represent |
| pseudoknots. `GrnadeModel` applies the released multi-conformation |
| geometric-vector encoder and masked autoregressive decoder over the 72 canonical |
| classes (classes the checkpoint does not predict have logit `-inf`), while |
| `GrnadePipeline` builds each sampled sequence's final target with the shared |
| design producer. |
|
|
| The implementation follows gRNAde v1.0.0 revision |
| `2453b18778a1981ac25f314790e5395f1e9ab218` and v0.3.2 revision |
| `e473636bef037be1e1b2516cf00af71e3334bd4f`. PyTorch Geometric carriers and |
| structure-file parsing do not cross the Model boundary. |
|
|
| ### Variants |
|
|
| Distinct explicit artifact identifiers select the ODesign `grnade.h5`, the |
| independently released v1 checkpoint, and all ten released v0.3.2 |
| autoregressive checkpoints. The latter retain their released one-, two-, |
| three-, or five-conformation Processor setting; split names do not change the |
| Model equation. |
|
|
| ### Links |
|
|
| - **Code**: [ofoldx.models.grnade](https://github.com/OTeam-AI4S/OFoldX/tree/main/ofoldx/models/grnade) |
| - **Method paper**: [gRNAde: Geometric Deep Learning for 3D RNA inverse design](https://arxiv.org/abs/2305.14749) |
| - **Experimental study**: [Generative inverse design of RNA structure and function with gRNAde](https://www.biorxiv.org/content/10.1101/2025.11.29.691298) |
| - **Developed by**: Chaitanya K. Joshi, Arian R. Jamasb, Ramon Viñas, Charles |
| Harris, Simon V. Mathis, Alex Morehead, Rishabh Anand, and Pietro Liò |
| - **Original repository**: [chaitjo/geometric-rna-design](https://github.com/chaitjo/geometric-rna-design) |
|
|
| ## Usage |
|
|
| Load the concrete design Pipeline from a converted repository: |
|
|
| ```python |
| from ofoldx.io import read_structure |
| from ofoldx.models.grnade import GrnadePipeline |
| |
| structure, report = read_structure("rna.cif") |
| pipeline = GrnadePipeline.from_repository("oteam/grnade") |
| result = pipeline.design(structure, secondary_structure="((((....))))", num_candidates=4, temperature=0.2) |
| ``` |
|
|
| `structure` holds one RNA instance, or `instance_id=` selects the target RNA |
| chain; the dot-bracket covers its RNA residues. `design=PositionSelection(...)` |
| restricts which residue identities may change. Each candidate reports total and |
| mean log probability, perplexity, and native recovery, and `result.records` |
| holds each candidate's design record. |
|
|
| Pass a sequence of aligned `Structure` values to condition one design on |
| multiple conformations: |
|
|
| ```python |
| result = pipeline.design((open_conformation, closed_conformation), secondary_structure="((((....))))") |
| ``` |
|
|
| The first conformation is the design target; later conformations contribute |
| structural features only and must contain the same RNA sequence. |
|
|
| For the v1 Pipeline, the dot-bracket's pairs are the secondary-structure pairs |
| supplied to the released graph; base-pair edges have higher priority than |
| overlapping spatial or sequence edges. Set `use_coordinates=False` to build the |
| released v1 1D+2D-only graph. |
|
|
| Released v0.3.2 repositories load through the paired legacy Pipeline: |
|
|
| ```python |
| from ofoldx.models.grnade import GrnadeV032Pipeline |
| |
| pipeline = GrnadeV032Pipeline.from_repository("oteam/grnade-v0.3.2-3state-all") |
| result = pipeline.design((first_conformation, second_conformation)) |
| ``` |
|
|
| The legacy graph has no base-pair or sequence-edge channel. |
| `use_coordinates=False` therefore produces zero geometric features and no |
| spatial edges. File parsing never enters the Model. |
|
|
| ## Training Details |
|
|
| OFoldX preserves the released model graph and differentiable teacher-forced |
| `forward` operation. `criterion(..., label_smoothing=...)` exposes the training |
| choice directly; the released training value was `0.05`. Dataset |
| construction, screening models, experiment tracking, and the upstream |
| training executable remain caller-owned. The raw teacher-forced Model output |
| is also available to custom training loops. |
|
|
| ## Citation |
|
|
| ```bibtex |
| @inproceedings{joshi2025grnade, |
| title={g{RNA}de: Geometric Deep Learning for 3D RNA inverse design}, |
| author={Joshi, Chaitanya K and Jamasb, Arian R and Vi{\~n}as, Ramon and |
| Harris, Charles and Mathis, Simon V and Morehead, Alex and |
| Anand, Rishabh and Li{\`o}, Pietro}, |
| booktitle={International Conference on Learning Representations}, |
| year={2025} |
| } |
| ``` |
|
|
| If OFoldX supports your research, also cite the OFoldX software: |
|
|
| ```bibtex |
| @software{chen2026ofoldx, |
| author = {Chen, Zhiyuan}, |
| title = {OFoldX}, |
| year = {2026}, |
| url = {https://github.com/OTeam-AI4S/OFoldX}, |
| } |
| ``` |
|
|
| ## Contact |
|
|
| Please use [OFoldX GitHub issues](https://github.com/OTeam-AI4S/OFoldX/issues) |
| for questions about this implementation or model card. Questions about the |
| original model should be directed to the gRNAde authors. |
|
|
| ## License |
|
|
| This model implementation is licensed under the |
| [GNU Affero General Public License](https://www.gnu.org/licenses/agpl-3.0.en.html). |
| The inspected upstream gRNAde source is MIT-licensed. |
|
|
| ```spdx |
| SPDX-License-Identifier: AGPL-3.0-or-later |
| ``` |
|
|
| The Pipeline is callable and supports staged execution with `prepare`, `forward`, |
| and `postprocess`. Prepared values retain the source and correspondence needed by |
| the scientific result; the concrete signatures describe each stage's controls. |
|
|
|
|
| ## Converted checkpoint |
|
|
| This repository contains converted model parameters under mit; the original terms and notices are preserved in `LICENSE`. OFoldX implementation licensing is described separately in `license.md` and `license-faq.md`. Conversion changes parameter names and native tensor layout; the upstream authors do not endorse this implementation. |
|
|
| - https://huggingface.co/chaitjo/gRNAde |
| - https://github.com/chaitjo/geometric-rna-design/blob/main/LICENSE |
| - https://huggingface.co/The-Institute-for-AI-Molecular-Design/ODesign |
|
|
