  We introduce AbDiffuser, an equivariant and physics-informed diffusion model
for the joint generation of antibody 3D structures and sequences. AbDiffuser is
built on top of a new representation of protein structure, relies on a novel
architecture for aligned proteins, and utilizes strong diffusion priors to
improve the denoising process. Our approach improves protein diffusion by
taking advantage of domain knowledge and physics-based constraints; handles
sequence-length changes; and reduces memory complexity by an order of
magnitude, enabling backbone and side chain generation. We validate AbDiffuser
in silico and in vitro. Numerical experiments showcase the ability of
AbDiffuser to generate antibodies that closely track the sequence and
structural properties of a reference set. Laboratory experiments confirm that
all 16 HER2 antibodies discovered were expressed at high levels and that 57.1%
of the selected designs were tight binders.
