DOMINO: Learning Domain Co-occurrence for Multidomain Protein Design (opens in new tab)

Multidomain proteins arise through the reuse and recombination of structural domains, yet natural architectures represent a sparse, structured sample of the possible domain-combination space. Here, we introduce DOMINO, a two-stage framework that learns domain co-occurrence from TED-annotated multidomain proteins and uses the learned patterns to generate new multidomain sequences. DOMIN, a contrastive retrieval model, embeds domains into a latent compatibility space and retrieves candidate par...