arXiv:2507.19755cs.LGcs.AI2025-07被引 4

用片段化序列分析预测酶的耐热性,提升工业酶设计效率

Modeling enzyme temperature stability from sequence segment perspective

  • 基于蛋白序列片段构建深度学习模型,捕捉不同区域对耐热性的贡献
  • 在新数据集上实现RMSE 24.03、MAE 18.09,相关性达0.33
  • 成功指导仅17次突变使切聚酯酶耐热性提升1.64倍,适合酶工程研究

开发具有特定热性能的酶对工业与科研应用至关重要,而热稳定性测定是关键步骤。实验方法耗时费力且成本高,现有计算方法常受限于数据量不足和分布不均。为此,我们构建了一个专用于酶热建模的高质量温度稳定性数据集,并提出全新的Segment Transformer深度学习框架,可高效准确预测酶的热稳定性。该模型在测试中取得RMSE 24.03、MAE 18.09,Pearson与Spearman相关系数分别为0.33。结果表明,基于生物学观察——蛋白序列不同片段对热行为影响不一,引入片段级表征显著提升性能。作为概念验证,我们将该模型应用于切聚酯酶工程,经仅17次突变后,其热处理后的相对活性提高1.64倍,同时保持催化功能完整。

原文摘要 · Abstract (English)

Developing enzymes with desired thermal properties is crucial for a wide range of industrial and research applications, and determining temperature stability is an essential step in this process. Experimental determination of thermal parameters is labor-intensive, time-consuming, and costly. Moreover, existing computational approaches are often hindered by limited data availability and imbalanced distributions. To address these challenges, we introduce a curated temperature stability dataset designed for model development and benchmarking in enzyme thermal modeling. Leveraging this dataset, we present the \textit{Segment Transformer}, a novel deep learning framework that enables efficient and accurate prediction of enzyme temperature stability. The model achieves state-of-the-art performance with an RMSE of 24.03, MAE of 18.09, and Pearson and Spearman correlations of 0.33, respectively. These results highlight the effectiveness of incorporating segment-level representations, grounded in the biological observation that different regions of a protein sequence contribute unequally to thermal behavior. As a proof of concept, we applied the Segment Transformer to guide the engineering of a cutinase enzyme. Experimental validation demonstrated a 1.64-fold improvement in relative activity following heat treatment, achieved through only 17 mutations and without compromising catalytic function.

酶工程深度学习热稳定性

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