AbDiffuser: Full-Atom Generation of in vitro Functioning Antibodies

Karolis Martinkus, Jan Ludwiczak, Kyunghyun Cho, Wei Ching Liang, Julien Lafrance-Vanasse, Isidro Hotzel, Arvind Rajpal, Yan Wu, Richard Bonneau, Vladimir Gligorijevic, Andreas Loukas

Research output: Contribution to journalConference articlepeer-review


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.

Original languageEnglish (US)
JournalAdvances in Neural Information Processing Systems
StatePublished - 2023
Event37th Conference on Neural Information Processing Systems, NeurIPS 2023 - New Orleans, United States
Duration: Dec 10 2023Dec 16 2023

ASJC Scopus subject areas

  • Computer Networks and Communications
  • Information Systems
  • Signal Processing


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