Towards Generative RNA Design With Tertiary Interactions

AO_SCPLOWBSTRACTC_SCPLOWThe function of an RNA molecule depends on its structure and a strong structure-to-function relationship is already achieved on the secondary structure level of RNA. Therefore, the secondary structure based design of RNAs is one of the major challenges in computational biology. A common approach to RNA design is inverse RNA folding. However, existing RNA design methods cannot invert all folding algorithms because they cannot represent all types of base interactions. In this work, we propose RNAinformer, a novel generative transformer based approach to the inverse RNA folding problem. Leveraging axial-attention, we directly model the secondary structure input represented as an adjacency matrix in a 2D latent space, which allows us to invert all existing secondary structure prediction algorithms. Consequently, RNAinformer is the first model capable of designing RNAs from secondary structures with all base interactions, including non-canonical base pairs and tertiary interactions like pseudoknots and base multiplets. We demonstrate RNAinformers state-of-the-art performance across different RNA design benchmarks and showcase its novelty by inverting different RNA secondary structure prediction algorithms.