arXiv:2603.18505cs.CV2026-03被引 1

AI从预测蛋白质静态结构,转向生成动态行为和多模态交互。

From Snapshots to Symphonies: The Evolution of Protein Prediction from Static Structures to Generative Dynamics and Multimodal Interactions

  • 用多模态融合序列、几何与文本信息统一建模蛋白质
  • 生成模型捕捉热力学一致的构象分布,支持动态模拟
  • 适合生物物理、药物设计与蛋白质工程研究者

蛋白质折叠问题因人工智能而彻底变革,从静态结构预测演进为动态构象集合与复杂生物分子互作的建模。本文系统审视人工智能驱动的蛋白质科学在五个维度的范式转变:统一多模态表征(整合序列、几何与文本知识);无需多序列比对的架构提升静态预测精度并实现全原子复合物建模;基于扩散模型与流匹配的生成框架,可捕捉符合热力学系综的构象分布;对蛋白-配体、蛋白-核酸及蛋白-蛋白复合物等异质互作的预测;以及功能推断,包括适应度景观、突变效应与文本引导的性质预测。文章批判性分析当前瓶颈,如数据分布偏差、机制可解释性不足、几何度量与生物物理现实的脱节,并提出未来方向:物理一致的生成模型、多模态基础架构与实验闭环系统。这一方法论演进标志着人工智能已从结构分析工具转变为能理解甚至重写生命动态语言的通用模拟器。

原文摘要 · Abstract (English)

The protein folding problem has been fundamentally transformed by artificial intelligence, evolving from static structure prediction toward the modeling of dynamic conformational ensembles and complex biomolecular interactions. This review systematically examines the paradigm shift in AI driven protein science across five interconnected dimensions: unified multimodal representations that integrate sequences, geometries, and textual knowledge; refinement of static prediction through MSA free architectures and all atom complex modeling; generative frameworks, including diffusion models and flow matching, that capture conformational distributions consistent with thermodynamic ensembles; prediction of heterogeneous interactions spanning protein ligand, protein nucleic acid, and protein protein complexes; and functional inference of fitness landscapes, mutational effects, and text guided property prediction. We critically analyze current bottlenecks, including data distribution biases, limited mechanistic interpretability, and the disconnect between geometric metrics and biophysical reality, while identifying future directions toward physically consistent generative models, multimodal foundation architectures, and experimental closed loop systems. This methodological transformation marks artificial intelligence's transition from a structural analysis tool into a universal simulator capable of understanding and ultimately rewriting the dynamic language of life.

蛋白质结构生成模型多模态生物物理

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