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Structure-based Antibody Renumbering

Created on 22 Sep 2026

Authors

del Alamo, D.

Abstract

Antibody numbering schemes like IMGT and Chothia assign each residue in the variable domain a consistent index based on substructural position. These annotations standardize sequences with different lengths, facilitating tasks ranging from engineering of individual molecules during drug development to large-scale curation of training data for de novo antibody design. Yet existing algorithms for performing this annotation process, termed renumbering, rely exclusively on amino acid sequence for inference. Consequently, these can fail when presented with unnatural or unusual features such as long CDRs or engineered insertions. To address this gap, this work introduces Structure-based Antibody Renumbering, abbreviated SAbR, a method that assigns these annotations from structure alone. SAbR shows comparable performance to sequence-based renumbering methods on held-out expert-annotated structures, as well as high agreement with sequence-based methods in a larger benchmark of diverse structures. It also outperforms peer methods on de novo-designed molecules, and shows higher success rates than renumbering by structural alignment. However, limited generalization performance is observed in more distantly related systems. Overall, these results establish structure-based renumbering as a robust alternative for natural and engineered antibodies when such data is available. Code and model weights are available on GitHub.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 22 Sep 2026.

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