arXiv:2511.10056cs.LG2025-11被引 1

用结构词汇的冗余性生成蛋白质构象多样性,快速建模蛋白动态。

From Static Structures to Ensembles: Studying and Harnessing Protein Structure Tokenization

  • 利用序列预训练嵌入弥合序列与结构语言的语义鸿沟。
  • 发现结构词汇存在大量几何相似的'同义词',可直接用于构象扰动。
  • 仅通过同义词替换即可生成高保真构象集合,适合快速分子动力学研究。

蛋白质结构分词将三维结构转化为离散或向量表示,实现结构与序列数据的融合。尽管近年已有诸多结构分词工作,但其离散表示的本质特性仍不清晰。本研究首先表明,语言模型在结构预测中成功应用结构标记,依赖于使用丰富的预训练序列嵌入来弥合序列与结构‘语言’之间的语义差距。对结构词汇本身的分析揭示出显著的语义冗余:多个不同标记对应几乎相同的局部几何,形成‘结构同义词’。这种冗余并非缺陷,反而可通过简单的‘同义词替换’策略,通过扰动预测结构生成多样化的构象集合。该计算成本极低的方法能准确再现蛋白质柔性,性能媲美当前最先进模型。本研究揭示了离散蛋白质结构表示的本质,并提出一种近乎即时的蛋白质动态建模方法。源代码见 https://github.com/IDEA-XL/TokenMD。

原文摘要 · Abstract (English)

Protein structure tokenization converts 3D structures into discrete or vectorized representations, enabling the integration of structural and sequence data. Despite many recent works on structure tokenization, the properties of the underlying discrete representations are not well understood. In this work, we first demonstrate that the successful utilization of structural tokens in a language model for structure prediction depends on using rich, pre-trained sequence embeddings to bridge the semantic gap between the sequence and structural "language". The analysis of the structural vocabulary itself then reveals significant semantic redundancy, where multiple distinct tokens correspond to nearly identical local geometries, acting as "structural synonyms". This redundancy, rather than being a flaw, can be exploited with a simple "synonym swap" strategy to generate diverse conformational ensembles by perturbing a predicted structure with its structural synonyms. This computationally lightweight method accurately recapitulates protein flexibility, performing competitively with state-of-the-art models. Our study provides fundamental insights into the nature of discrete protein structure representations and introduces a powerful, near-instantaneous method for modeling protein dynamics. Source code is available in https://github.com/IDEA-XL/TokenMD.

蛋白质结构结构分词构象生成动态建模

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