ImmuneBuilder: Deep-Learning models for predicting the structures of immune proteins

Immune receptor proteins play a key role in the immune system and have shown great promise as biotherapeutics. The structure of these proteins is critical for understanding their antigen binding properties. Here, we present ImmuneBuilder, a set of deep learning models trained to accurately predict the structure of antibodies (ABodyBuilder2), nanobodies (NanoBodyBuilder2) and T-Cell receptors (TCRBuilder2). We show that ImmuneBuilder generates structures with state of the art accuracy while being far faster than AlphaFold2. For example, on a benchmark of 34 recently solved antibodies, ABodyBuilder2 predicts CDR-H3 loops with an RMSD of 2.81 angstrom, a 0.09 angstrom improvement over AlphaFold-Multimer, while being over a hundred times faster. Similar results are also achieved for nanobodies, (NanoBodyBuilder2 predicts CDR-H3 loops with an average RMSD of 2.89 angstrom, a 0.55 angstrom improvement over AlphaFold2) and TCRs. By predicting an ensemble of structures, ImmuneBuilder also gives an error estimate for every residue in its final prediction. ImmuneBuilder is made freely available, both to download (https://github.com/oxpig/ImmuneBuilder) and to use via our webserver (http://opig.stats.ox.ac.uk/webapps/newsabdab/sabpred). We also make available structural models for similar to 150 thousand non-redundant paired antibody sequences (https://doi.org/10.5281/zenodo.7258553).

Automated summary

Immune receptor proteins are important in the immune system and have potential as biotherapeutics. A deep learning model called ImmuneBuilder is presented, which accurately predicts the structure of antibodies, nanobodies, and T-cell receptors. ImmuneBuilder outperforms AlphaFold2 in terms of accuracy and speed.