使用全方位多点突变生成管道的合理蛋白质工程
Lingxi Fan1, Hui Wang1, Han Gao2
1National Key Laboratory of Agricultural Microbiology, Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
iScience
|September 2, 2025
概括
这项研究引入了一个新的蛋白质工程管道,使用生成模型来创建和选择功能性蛋白质. 该方法成功增强了蛋白酶突变的热稳定性和工程酶的溶酶活性.
科学领域:
- 蛋白质工程
- 计算生物学
- 生物技术
背景情况:
- 生成模型通过创建大数据集来加速蛋白质设计.
- 识别这些数据集中的功能序列是一个关键挑战.
研究的目的:
- 使用生成模型开发蛋白质工程的新型管道.
- 增强蛋白质的特性,如热稳定性和酶活性.
主要方法:
- 基于预先训练的蛋白质BERT模型开发了全向多点变异 (ODM) 模型.
- 产生了10万个突变蛋白质序列.
- 使用突变效应预测排列序列,并开发了热稳定性和酶活性的特定模型.
主要成果:
- 62. 5% 的蛋白酶突变体在两个设计周期后显示出更好的热稳定性.
- 50% 的溶酶突变体表现出增强的细菌溶解活性.
- 这种管道有效地识别并设计了具有增强功能的蛋白质.
结论:
- 集成管道成功设计了具有所需功能增强的蛋白质.
- 这种方法为新的蛋白质设计和优化提供了强有力的策略.
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