arXiv:2605.00182cs.LG2026-05中稿 · ICML被引 1

提出可模拟蛋白质进化过程的生成模型,支持精准编辑与变长演化。

Towards A Generative Protein Evolution Machine with DPLM-Evo

论文配图:Towards A Generative Protein Evolution Machine with DPLM-Evo
图 1 · 摘自论文原文
  • 基于显式突变/插入/删除操作的扩散框架,更贴近生物进化机制。
  • 在ProteinGym上实现单序列突变预测新纪录,准确率提升显著。
  • 适合需要蛋白设计、定向优化或模拟进化的研究人员使用。

蛋白质在物理和功能约束下逐步演化。蛋白语言模型从海量序列中学习进化约束,基于离散扩散的蛋白语言模型(如DPLM)在理解与生成方面表现优异。然而,现有DPLM多依赖掩码扩散,违背了生物直觉:蛋白质通过累积编辑演化,而非从掩码中涌现。这导致其缺乏对替换与插入/删除(indel)操作的显式预训练目标,限制了优化式后编辑与灵活引导生成。为此,我们提出DPLM-Evo,一种显式预测替换、插入与删除操作的演化型离散扩散框架。DPLM-Evo将上采样长度的隐空间与可变长度观测序列空间解耦,使indel感知生成成为可能。为进一步契合真实进化,引入上下文感知的演化噪声核,生成具生物学意义的上下文依赖突变模式。在多个任务中,DPLM-Evo提升序列理解能力,并在ProteinGym单序列设置下达到最新突变效应预测性能。它还支持变长模拟进化及通过显式编辑轨迹对已有蛋白进行后编辑与优化。

原文摘要 · Abstract (English)

Proteins are shaped by gradual evolution under biophysical and functional constraints. Protein language models learn rich evolutionary constraints from large-scale sequences, and discrete diffusion-based protein language models~(\eg, DPLMs) are promising for both understanding and generation. However, existing DPLMs typically rely on masked diffusion that contradicts a simple biological intuition: proteins evolve through accumulated edits, not by emerging from masks. Consequently, these frameworks lack explicit pretraining objectives for substitution and insertion/deletion (indel) operations, limiting both optimization-style post-editing and flexible guided generation. To address these limitations, we present DPLM-Evo, an evolutionary discrete diffusion framework that explicitly predicts substitution, insertion, and deletion operations during denoising. DPLM-Evo decouples an upsampled-length latent alignment space from the variable-length observed sequence space, which makes indel-aware generation tractable. To better align substitutions with real evolution, we further introduce a contextualized evolutionary noising kernel that produces biologically informed, context-dependent mutation patterns. Across tasks, DPLM-Evo improves sequence understanding and achieves state-of-the-art mutation effect prediction performance on ProteinGym in the single-sequence setting. It also enables variable-length simulated evolution, and post-editing/optimization of existing proteins via explicit edit trajectories.

蛋白生成扩散模型演化建模序列编辑

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