Weihenstephan-Triesdorf University of Applied Sciences

RNA inverse folding has long relied on iterative optimization scored by an external folding algorithm, which is sensitive to initialization and prone to local optima. This work defines multinomial diffusion directly over nucleotide sequences, guides denoising with a target secondary structure, and compares a 2D contact-map projection with a purely 1D pairing-aware architecture. On the in-distribution test set, the 2D and 1D models reach median normalized RNAforester similarities of 0.82 and 0.79, while generated sequences stay close to random-sequence diversity.

RNA inverse folding has long relied on iterative optimization scored by an external folding algorithm, which is sensitive to initialization and prone to local optima. This work defines multinomial diffusion directly over nucleotide sequences, guides denoising with a target secondary structure, and compares a 2D contact-map projection with a purely 1D pairing-aware architecture. On the in-distribution test set, the 2D and 1D models reach median normalized RNAforester similarities of 0.82 and 0.79, while generated sequences stay close to random-sequence diversity.