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IgGM2: An All-Atom Foundation Model for Adaptive Immune Receptor Design

Created on 10 Jul 2026

Authors

Ma, J., Wu, F., Yao, L., Gao, J., Wang, R., Li, Q., Yang, N., Jiang, S., Huang, D., Pan, X., Zhu, Y., Hou, T., Yao, J., Yan, J.

Abstract

Accurate immune receptor design requires modeling the coupled variation of amino-acid sequence, full-atom conformation, and target-binding geometry across antibodies, nanobodies, and T-cell receptors (TCRs). Existing methods often address only part of this problem, either by separating structure generation from sequence design, relying on fixed-backbone inverse folding, or focusing on a single receptor class. We introduce IgGM2, a unified all-atom generative framework for immune receptor structure prediction and CDR sequence-structure co-design. IgGM2 follows a structure-to-design strategy: it first learns how immune receptors are positioned around fixed target structures, and then transfers this target-conditioned structural prior to CDR design. Unlike modular design pipelines, IgGM2 jointly generates CDR residue identities and full-atom receptor structures, allowing framework geometry to adapt to designed CDRs without separate inverse folding or external sidechain packing. Unlike continuous residue encodings based on virtual-atom geometry, IgGM2 keeps sequence prediction explicit while using atom14 placeholders only for full-atom representation. On structure prediction benchmarks, IgGM2 better captures receptor-target spatial relationships than AlphaFold3 on FoldBench and achieves strong performance on TCR-pMHC modeling. On sequence design benchmarks, IgGM2 improves amino-acid recovery and Rosetta-based interface preference metrics, suggesting more favorable generated binding interfaces. These results support IgGM2 as a unified all-atom framework for adaptive immune receptor structure prediction and design.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 10 Jul 2026.

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