Good news! Impressive! This could be a breakthrough!
"An AI system has designed entire antibodies from scratch that can hit disease targets with atomic-level accuracy. Scientists in Nobel laureate David Baker’s lab used their RFdiffusion model to create antibodies that latch on to specific sites on viruses, bacterial toxins and cancer-linked proteins, with cryo-electron microscopy confirming the precise fits.
The advance cuts down the need for labour-intensive antibody screening. The early designs aren’t ready to be used in therapeutics, but is the first proof-of-concept that computers can build functional antibodies in silico, which has the potential to speed up drug discovery. The next step will be understanding how they work in the body."
From the abstract:
"Despite the central role of antibodies in modern medicine, no method currently exists to design novel, epitope-specific antibodies entirely in silico.
Instead, antibody discovery currently relies on immunization, random library screening or the isolation of antibodies directly from patients.
Here we demonstrate that combining computational protein design using a fine-tuned RFdiffusion network with yeast display screening enables the de novo generation of antibody variable heavy chains (VHHs), single-chain variable fragments (scFvs) and full antibodies that bind to user-specified epitopes with atomic-level precision.
We experimentally characterize VHH binders to four disease-relevant epitopes. Cryo-electron microscopy confirms the binding pose of designed VHHs targeting influenza haemagglutinin and Clostridium difficile toxin B (TcdB).
A high-resolution structure of the influenza-targeting VHH confirms atomic accuracy of the designed complementarity-determining regions (CDRs). Although initial computational designs exhibit modest affinity (tens to hundreds of nanomolar Kd), affinity maturation using OrthoRep enables production of single-digit nanomolar binders that maintain the intended epitope selectivity.
We further demonstrate the de novo design of scFvs to TcdB and a PHOX2B peptide–MHC complex by combining designed heavy-chain and light-chain CDRs.
Cryo-electron microscopy confirms the binding pose for two distinct TcdB scFvs, with high-resolution data for one design verifying the atomically accurate design of the conformations of all six CDR loops. Our approach establishes a framework for the computational design, screening and characterization of fully de novo antibodies with atomic-level precision in both structure and epitope targeting."
Fig. 1: Overview of RFdiffusion for antibody design.
Fig. 3: Cryo-EM structural characterization of de novo-designed VHH binding to influenza haemagglutinin and TcdB.
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