arXiv:2505.12511cs.CL2025-05被引 4

DS-ProGen通过融合骨架与表面信息,提升蛋白质序列设计精度。

DS-ProGen: A Dual-Structure Deep Language Model for Functional Protein Design

  • 结合骨架坐标与表面化学几何特征进行氨基酸预测
  • 在PRIDE数据集上达到61.47%的序列恢复率,领先现有方法
  • 擅长预测与配体、离子、RNA等分子的相互作用,适合功能蛋白设计

逆向蛋白质折叠(IPF)是蛋白质设计中的关键任务,旨在设计出能正确折叠为指定三维结构的氨基酸序列。尽管近年取得进展,现有方法多仅依赖骨架坐标或分子表面特征之一,难以充分捕捉精确序列预测所需的复杂化学与几何约束。为此,我们提出DS-ProGen,一种用于功能蛋白质设计的双结构深度语言模型,融合骨架几何与表面层次表征。通过将骨架坐标及表面化学和几何描述符引入下一氨基酸预测范式,DS-ProGen能够生成具有功能性且结构稳定的序列,同时满足全局与局部构象约束。在PRIDE数据集上,DS-ProGen达到当前最优的61.47%序列恢复率,表明多模态结构编码的协同优势。此外,其在预测与多种生物伙伴(包括配体、离子、RNA)相互作用方面表现优异,验证了其强大的功能保留能力。

原文摘要 · Abstract (English)

Inverse Protein Folding (IPF) is a critical subtask in the field of protein design, aiming to engineer amino acid sequences capable of folding correctly into a specified three-dimensional (3D) conformation. Although substantial progress has been achieved in recent years, existing methods generally rely on either backbone coordinates or molecular surface features alone, which restricts their ability to fully capture the complex chemical and geometric constraints necessary for precise sequence prediction. To address this limitation, we present DS-ProGen, a dual-structure deep language model for functional protein design, which integrates both backbone geometry and surface-level representations. By incorporating backbone coordinates as well as surface chemical and geometric descriptors into a next-amino-acid prediction paradigm, DS-ProGen is able to generate functionally relevant and structurally stable sequences while satisfying both global and local conformational constraints. On the PRIDE dataset, DS-ProGen attains the current state-of-the-art recovery rate of 61.47%, demonstrating the synergistic advantage of multi-modal structural encoding in protein design. Furthermore, DS-ProGen excels in predicting interactions with a variety of biological partners, including ligands, ions, and RNA, confirming its robust functional retention capabilities.

蛋白质设计深度学习多模态建模

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