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Benchmarking antigen-aware inverse folding methods for antibody design.

Janusz, B.; Chomicz, D.; Wrobel, S.; Dudzic, P.; Polasa, A.; Martin, K.; Darnell, S.; Comeau, S. R.; Krawczyk, K.

2025-08-07 bioinformatics
10.1101/2025.08.05.668698 bioRxiv
Show abstract

Computational antibody design has seen many recent advances pioneered via the use of language models and advanced structure prediction tools. Developing a de novo antibody against a specific antigen requires structural awareness that most language models lack. A prominent class of machine learning methods combining the best of language model and structural worlds is inverse folding. This approach aims to predict a sequence that would fit a given structure. Such methods are now increasingly used to predict alternate sequences given a structure of a binder. It is known that, just like language models, such methods have certain predictive power in identifying binders. Here we performed a set of tests to reveal where, if at all, such methods provide value in the realistic setting of antibody discovery.

Published in Bioinformatics Advances (predicted rank #3) · training set

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