La-Ribo: RNA Co-Design via Geometry-Latent Flow Matching
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Abstract (arXiv)
RNA function arises from the coupling of nucleotide sequence and three-dimensional structure, motivating their joint design. Coordinating global folding with nucleotide-level detail remains challenging under limited structural supervision. We introduce La-Ribo, a generative framework for RNA sequence-structure co-design via geometry-latent flow matching. La-Ribo retains a sparse phosphate-sugar--base scaffold and encodes nucleotide identity and local conformation in residue-wise latents. A shared flow network generates both jointly, and an RNA-specific decoder then reconstructs all heavy atoms. To expand supervision, we construct a quality-controlled corpus of 168,561 RNA structures, integrating experimental data with predictions from three folding models, including 10,631 MSA-supported structures generated in this work. La-Ribo improves designability and codesignability over the evaluated baselines across sampling budgets and two refolding models, and the same prior supports scaffold-conditioned inverse folding without additional training.
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- 2024RNAFlow: RNA Structure & Sequence Design via Inverse Folding-Based Flow Matching
- 2026RiboSphere: Learning Unified and Efficient Representations of RNA Structures
- 2026TANGO: RNA Topology and Geometry Co-Design
- 2025RiboGen: RNA Sequence and Structure Co-Generation with Equivariant MultiFlow
- 2026RNA Design via Conditioned Flow Matching and Finite-Policy Reinforcement Learning
- 2026Structure-based RNA Design by Step-wise Optimization of Latent Diffusion Model
- 2026RIDER: 3D RNA Inverse Design with Reinforcement Learning-Guided Diffusion