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Protenix-v2: Broadening the Reach of Structure Prediction and Biomolecular Design

Zhang, Y.; Gong, C.; Sun, J.; Guan, J.; Ren, M.; Xue, S.; Zhang, H.; Ma, W.; Liu, Z.; Chen, X.; Xiao, W.

2026-04-11 molecular biology
10.64898/2026.04.10.717613 bioRxiv
Show abstract

Advances in biomolecular modeling have broadened the range of problems addressable by structure prediction and design models. Here, we present results from Protenix-v2, a system spanning high-accuracy structure prediction and biomolecular design. On the structure prediction side, Protenix-v2 achieves antibody-antigen success rates with up to 13-point gains over Protenix-v1, while 5-seed performance surpasses previous 1000-seed results. On the design side, Protenix-v2 demonstrates a 100% target-level success rate in novelty-controlled VHH-Fc campaigns, reaching hit rates up to 48%. Crucially, the model enables hit discovery on difficult GPCR targets with hit rates of 16%-88% (VHH-Fc) and up to 50% (mAb) under 16-30 testing budgets per target. Resulting hits show high developability and diversity. Beyond antibody tasks, we report improved ligand-related plausibility and successful cross-variant SARS-CoV-2 spike RBD mini-binder design. These results establish Protenix-v2 as a robust and powerful model for accelerated drug discovery.

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