SeedProteo: Accurate De Novo All-Atom Design of Protein Binders

Fuente: arXiv
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Autores principales: Qu, Wei, Ma, Yiming, Ye, Fei, Lu, Chan, Zhou, Yi, Zhang, Kexin, Wang, Lan, Gui, Minrui, Gu, Quanquan
Formato: Preprint
Publicado: 2025
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author Qu, Wei
Ma, Yiming
Ye, Fei
Lu, Chan
Zhou, Yi
Zhang, Kexin
Wang, Lan
Gui, Minrui
Gu, Quanquan
author_facet Qu, Wei
Ma, Yiming
Ye, Fei
Lu, Chan
Zhou, Yi
Zhang, Kexin
Wang, Lan
Gui, Minrui
Gu, Quanquan
contents We present SeedProteo, a diffusion-based model for de novo all-atom protein design. We demonstrate how to repurpose a cutting-edge folding architecture into a powerful generative design framework by effectively integrating self-conditioning features. Extensive benchmarks highlight the model's capabilities across two distinct tasks: in unconditional generation, SeedProteo exhibits superior length generalization and structural diversity, maintaining robustness for long sequences and complex topologies; in binder design, it achieves state-of-the-art performance among open-source methods, attaining the highest in-silico design success rates, structural diversity and novelty. Finally, we validate SeedProteo through wet-lab assays on two therapeutic targets, achieving hit rates of 70%-80% and picomolar-level binding affinities, establishing leading results. To facilitate community adoption, we provide public access to SeedProteo via a webserver (https://seedfold.io/proteinDesign).
format Preprint
id arxiv_https___arxiv_org_abs_2512_24192
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle SeedProteo: Accurate De Novo All-Atom Design of Protein Binders
Qu, Wei
Ma, Yiming
Ye, Fei
Lu, Chan
Zhou, Yi
Zhang, Kexin
Wang, Lan
Gui, Minrui
Gu, Quanquan
Biomolecules
We present SeedProteo, a diffusion-based model for de novo all-atom protein design. We demonstrate how to repurpose a cutting-edge folding architecture into a powerful generative design framework by effectively integrating self-conditioning features. Extensive benchmarks highlight the model's capabilities across two distinct tasks: in unconditional generation, SeedProteo exhibits superior length generalization and structural diversity, maintaining robustness for long sequences and complex topologies; in binder design, it achieves state-of-the-art performance among open-source methods, attaining the highest in-silico design success rates, structural diversity and novelty. Finally, we validate SeedProteo through wet-lab assays on two therapeutic targets, achieving hit rates of 70%-80% and picomolar-level binding affinities, establishing leading results. To facilitate community adoption, we provide public access to SeedProteo via a webserver (https://seedfold.io/proteinDesign).
title SeedProteo: Accurate De Novo All-Atom Design of Protein Binders
topic Biomolecules
url https://arxiv.org/abs/2512.24192