FoldAbS: Repurposing the Protein Folding Model as a Foundation Encoder for Antibody Screening
Jun WuiD, Fandi WuiD, Xinyuan ZhuiD, Dawei HuangiD, Kaiwen ChengiD, Jianzhu MaiD, Fuli FengiD, Jianhua YaoiD
Abstract
Therapeutic antibody screening requires prioritizing antibody candidates across specificity, affinity, and developability. Current pipelines typically silo these objectives and underuse structural information that governs antibody-antigen recognition. To address these inefficacies, we introduce FoldAbS, a unified supervised screening framework that reconceptualizes protein folding models as frozen foundation encoders, exploiting their internal representations to capture rich sequence, geometric, and interaction dynamics well beyond basic structure prediction. By coupling the folding model with lightweight, task-specific heads, FoldAbS seamlessly evaluates all three therapeutic criteria within a single architecture. Instantiating this framework with the open-source Protenix model (FoldAbS-Px) yields consistent improvements over baseline approaches, achieving significant performance gains of up to 13.1%, 9.2%, and 6.2% in specificity, affinity, and developability, respectively. Collectively, these results reposition protein folding models from structure predictors and confidence scorers into reusable foundation encoders for comprehensive and supervised antibody screening. Our code is available at https://github.com/nohandsomewujun/FoldAbS.
02 /Specification & Classification
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