arXiv:2504.04453q-bio.BMcs.AI2025-04被引 4

用语言模型生成高亲和力蛋白结合剂,不依赖三维结构。

Prot42: a Novel Family of Protein Language Models for Target-aware Protein Binder Generation

  • 基于自回归解码器架构,从序列学习深层进化与功能信息。
  • 支持长达8192个氨基酸的序列建模,突破传统限制。
  • 适合快速设计靶向蛋白或特异性结合DNA的分子,开源可用。

解锁下一代生物技术和治疗创新需克服传统蛋白质工程方法固有的复杂性与资源密集性。当前基于生成式AI的计算方法通常依赖目标蛋白的三维结构和特定结合位点,如AlphaProteo和RFdiffusion所展示。本文探索使用蛋白质语言模型(pLMs)进行高亲和力结合剂的设计。我们提出Prot42,一个在海量未标注蛋白质序列上预训练的新一代pLM家族。通过借鉴自然语言处理中突破性进展的自回归、仅解码器架构,Prot42深刻捕捉蛋白质的演化、结构与功能信息,显著拓展了仅基于语言的计算蛋白质设计能力。其模型可处理最长达8,192个氨基酸的序列,远超常规限制,实现对大型蛋白及复杂多域序列的精准建模。实证表明,Prot42在生成高亲和力蛋白结合剂和序列特异性DNA结合蛋白方面表现卓越。本研究提出的模型已公开,为科学界提供高效、精准的快速蛋白质工程计算工具。

原文摘要 · Abstract (English)

Unlocking the next generation of biotechnology and therapeutic innovation demands overcoming the inherent complexity and resource-intensity of conventional protein engineering methods. Recent GenAI-powered computational techniques often rely on the availability of the target protein's 3D structures and specific binding sites to generate high-affinity binders, constraints exhibited by models such as AlphaProteo and RFdiffusion. In this work, we explore the use of Protein Language Models (pLMs) for high-affinity binder generation. We introduce Prot42, a novel family of Protein Language Models (pLMs) pretrained on vast amounts of unlabeled protein sequences. By capturing deep evolutionary, structural, and functional insights through an advanced auto-regressive, decoder-only architecture inspired by breakthroughs in natural language processing, Prot42 dramatically expands the capabilities of computational protein design based on language only. Remarkably, our models handle sequences up to 8,192 amino acids, significantly surpassing standard limitations and enabling precise modeling of large proteins and complex multi-domain sequences. Demonstrating powerful practical applications, Prot42 excels in generating high-affinity protein binders and sequence-specific DNA-binding proteins. Our innovative models are publicly available, offering the scientific community an efficient and precise computational toolkit for rapid protein engineering.

蛋白质设计生成模型语言模型生物工程

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