<i>De Novo</i> Antibody Design with SE(3) Diffusion

We introduce <i>IgDiff</i>, an antibody variable domain diffusion model based on a general protein backbone diffusion framework, which was extended to handle multiple chains. Assessing the designability and novelty of the structures generated with our model, we find that <i>IgDiff</i> produces highly designable antibodies that can contain novel binding regions. The backbone dihedral angles of sampled structures show good agreement with a reference antibody distribution. We verify these designed antibodies experimentally and find that all express with high yield. Finally, we compare our model with a state-of-the-art generative backbone diffusion model on a range of antibody design tasks, such as the design of the complementarity determining regions or the pairing of a light chain to an existing heavy chain, and show improved properties and designability.