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bioRxiv · 10.1101/2025.08.18.670959

Conditional Protein Structure Generation with Protpardelle-1c

Lu, T.·Shuai, R. W.·Kouba, P.·Li, Z.·Chen, Y.·Shirali, A.·Kim, J.·Huang, P.
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Abstract

We present Protpardelle-1c, a collection of protein structure generative models with robust motif scaffolding and support for multi-chain complex generation under hotspot-conditioning. Enabling sidechain-conditioning to a backbone-only model increased Protpardelle-1cs MotifBench score from 4.97 to 28.16, outperforming RFdiffusions 21.27. The crop-conditional all-atom model achieved 208 unique solutions on the La-Proteina all-atom motif scaffolding benchmark, on par with La-Proteina while having ~10 times fewer parameters. At 22M parameters, Protpardelle-1c enables rapid sampling, taking 40 minutes to sample all 3000 MotifBench backbones on an NVIDIA A100-80GB, compared to 31 hours for RFdiffusion.

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Lu, T., Shuai, R. W., Kouba, P., Li, Z., Chen, Y., Shirali, A., Kim, J., Huang, P.. 2025-08-18. Conditional Protein Structure Generation with Protpardelle-1c. https://doi.org/10.1101/2025.08.18.670959

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