RiboWeave: Integrating Secondary and Tertiary Structure Knowledge into Sequence Representations for RNA Aptamer Design

RNA aptamers are single-stranded nucleic acid molecules that bind targets with high affinity and specificity, with applications in diagnostics, targeted therapeutics, and drug delivery. High-throughput screening yields aptamer candidates, but validating screened sequences is time-consuming and labor-intensive, motivating computational models to accelerate aptamer discovery. Screening data provide a natural source of supervision, yet typically contain only sequences and enrichment measurements without matched structural information. Moreover, modeling RNA-protein interactions requires integrating information across modalities and granularities, as sequence, secondary structure, and tertiary structure contribute at both local and whole-molecule levels. We present RiboWeave, a framework that transfers structural knowledge into sequence representations through nucleotide-level pairing and geometry prediction and molecule-level contrastive alignment with structural representations. Its Hybrid version combines the resulting representations through task-specific fusion, and all RiboWeave models require only RNA sequences at inference. Cross-modal evaluation reveals both shared and modality-specific structural information, while joint supervision balances the two structural modalities. For downstream activity prediction, RiboWeave Hybrid achieves the highest macro $R^2$ across CD3 and cMYC under cluster-disjoint splits, outperforming both single-modality cross-granularity variants and single-granularity capacity controls. In a common generation framework, RiboWeave Hybrid achieves the highest novel-sequence fractions while maintaining strong predicted activity and high sequence diversity across CD3 and cMYC. These results support the utility of multimodal and multigranular structural supervision for sequence-only aptamer activity prediction and computational design.