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

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 structure prediction and CDR sequence–structure co-design. For structure prediction, IgGM2 models receptor monomers from sequence and receptor–target complexes conditioned on fixed target structures and epitope context. For CDR design, a two-stage sampler first jointly generates CDR sequences and backbone conformations, then refines full-atom receptor structures with the generated sequences fixed. This allows receptor frameworks to adapt to designed CDRs without separate inverse folding or external side-chain packing. On structure prediction benchmarks, IgGM2 achieves strong performance on FoldBench and in TCR–pMHC modeling. On sequence design benchmarks, IgGM2 achieves competitive amino-acid recovery and improves 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.