Base-and-Sugar Dual-Frame Flow Matching for RNA Co-Design

Current frame-based RNA generative models represent each nucleotide with a single rigid coordinate frame. However, our analysis of seven nucleotide frame constructions across $11,497$ static RNA chains and $31,432$ multi-state relation groups reveals a clear trade-off: base-centered frames better preserve base-mediated relations, whereas sugar-centered frames better support sugar-phosphate backbone reconstruction. Motivated by this complementarity, we introduce DuetRNA, a joint sequence-structure generation model for RNA co-design that performs $\mathrm{SE}(3)$ flow matching over coupled base-and-sugar frames. Empirically, we evaluate DuetRNA under both the inverse-folded (IF) backbone-design protocol and generated-sequence (GS) co-design protocol. DuetRNA improves scTM-validity over the strongest matched baselines by 7.67 and 4.33 % under IF and GS, respectively. Controlled ablations further support the necessity of the dual-frame modeling in DuetRNA.