快速准确的蛋白质结构数据库搜索使用反向折叠模型和对比学习.
Qiuyi Lyu1, Hong Wei2, Shuaishuai Chen3
1MOE Frontiers Science Center for Nonlinear Expectations, Research Center for Mathematics and Interdisciplinary Sciences, Shandong University, Qingdao 266237, China.
Journal of chemical information and modeling
|November 26, 2025
概括
我们开发了mTM-align2,一种快速而准确的蛋白质结构搜索方法. 它使用先进的嵌入和对齐来快速在大型数据库中找到类似的蛋白质结构.
科学领域:
- 结构生物学是结构生物学.
- 生物信息学是一种生物信息学.
- 计算化学是一种计算化学.
背景情况:
- 由于大量可用的结构,搜索蛋白质结构数据库越来越困难.
- 现有的方法在进行大规模蛋白质结构比较时,难以达到速度和准确性.
研究的目的:
- 引入mTM-align2,一种新的两步方法,用于快速准确的蛋白质结构数据库搜索.
- 为识别结构相似的蛋白质提供一个计算高效的工具.
主要方法:
- 使用预训练的逆折叠模型 (ESM-IF) 和3D泽尼克多项式来生成蛋白质结构嵌入.
- 通过在数百万个结构对上训练的对比学习网络优化嵌入.
- 采用快速结构调整程序来完善顶级候选结构.
主要成果:
- 在蛋白质结构数据库搜索中,mTM-align2实现了与领先的方法相比具有竞争力的性能.
- 该方法在几秒钟内以超过90%的精度对前10个结果进行单体结构搜索.
- 由mTM-align2生成的嵌入是结构上有信息的,捕获全球蛋白质特征.
结论:
- mTM-align2在快速准确的蛋白质结构数据库搜索方面取得了重大进展.
- 开发的嵌入物有效地代表了蛋白质的全球结构特征.
- 有一个Web服务器可以访问mTM-align2工具.
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