Computational Antibody Papers

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protein design
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2026
TitleKey points

  • 2026-01-20

    Origin-1: a generative AI platform for de novo antibody design against novel epitopes

    • protein design
    • De novo platform for epitope-specific antibody design against “zero-prior” targets, i.e. antigen sites with no known antibody–antigen or protein–protein complex structures and limited homology to previously solved interfaces.
    • The method combines three tightly integrated components: AbsciDiff, an all-atom diffusion model fine-tuned from Boltz-1 to generate epitope-conditioned antibody–antigen complex structures; IgDesign2, a structure-conditioned paired heavy–light CDR sequence design model; and AbsciBind, a modified AF-Unmasked / AlphaFold-Multimer–based scoring protocol using ipTM-derived interface confidence to rank and filter designs.
    • The platform was evaluated on 10 zero-prior protein targets, with fewer than 100 antibody designs per target advanced to experimental testing; specific binders were successfully identified for 4 targets (COL6A3, AZGP1, CHI3L2, IL36RA).
    • Experimental validation demonstrated both structural and functional accuracy, including cryo-EM confirmation at near-atomic resolution (DockQ 0.73–0.83) for two targets and AI-guided affinity maturation yielding a functional IL36RA antagonist with ~100 nM potency.

  • 2026-01-09

    Drug-like antibodies with low immunogenicity in human panels designed with Latent-X2

    • protein design
    • All-atom, zero-shot generative model that designs antibody sequence and structure directly in complex with a target from epitope-conditioned prompts.
    • One specifies target, epitope, modality and the algorithm produces designs.
    • They tested 4–24 designs per target, achieving 50% target-level success, producing VHHs and scFvs with pico- to nanomolar affinities (best ≈ 26 pM).
    • Designed antibodies show therapeutic-grade developability (expression, aggregation, hydrophobicity, polyreactivity, stability) without optimization via wetlab validation.
    • Human PBMC assays (10 donors) show no detectable immunogenicity for representative de novo nanobodies.