Atomically accurate de novo design of antibodies with RFdiffusion.

ABSTRACT: Despite the central role that antibodies play in modern medicine, there is currently no method to design novel antibodies that bind a specific epitope entirely in silico. Instead, antibody discovery currently relies on animal immunization or random library screening approaches. Here, we demonstrate that combining computational protein design using a fine-tuned RFdiffusion network alongside yeast display screening enables the generation of antibody variable heavy chains (VHHs) and single chain variable fragments (scFvs) that bind user-specified epitopes with atomic-level precision. To verify this, we experimentally characterized VHH binders to four disease-relevant epitopes using multiple orthogonal biophysical methods, including cryo-EM, which confirmed the proper Ig fold and bindin

SUBMITTER: Bennett NR 

PROVIDER: S-EPMC10983868 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature