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Fast retrieval of structurally similar antibodies from large sequence databases with AbSLang

Wang, E. J. D.; Spoendlin, F. C.; Greenshields-Watson, A.; Taylor, C. R.; Deane, C. M.

2026-08-11 bioinformatics
10.64898/2026.08.05.742817 bioRxiv
Show abstract

The first steps in antibody therapeutic discovery involve identification of sequences with desirable binding properties. A way of finding these lead molecules is through the search of large sequence databases. Current methods, due to the size of databases, rely on germline or complementarity-determining-region (CDR) sequence identities, overlooking structurally similar antibodies with divergent sequences which can have identical binding properties . To address this, we introduce AbSLang, a model trained for pairwise CDR RMSD prediction using a contrastive learning approach. We demonstrate that AbSLang has comparable accuracy to exact RMSD calculation after explicit structure prediction with state-of-the-art models. Building on this model, we implemented AbSLang-search, a pipeline for retrieval of structurally similar antibodies from large sequence databases. AbSLang-search is highly compute efficient and allows to search datasets with 10 million sequences in less than 2 seconds.

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