[P450Diff2:一种基于扩散模型的方法,用于生成P450酶序列]
Xudong Han1,2,3, Xiaotong Shao1,2, Huimin Chen1,2
1School of Biological Engineering, Tianjin University of Science & Technology, Tianjin 300457, China.
Sheng wu gong cheng xue bao = Chinese journal of biotechnology
|December 29, 2025
概括
新的人工智能模型P450Diff2可以生成多样而准确的人工细胞染色体P450酶序列. 这种方法显著改进了以前的模型,显示了快速de novo酶工程的希望.
科学领域:
- 生物化学和分子生物学
- 生物信息学和计算生物学
- 酶工程是什么? 酶工程是什么?
背景情况:
- 细胞染色体P450酶是关键的氧化还原酶,参与药物代谢,二次代谢和污染物生物转化.
- 产生多样化和高保真度的人造P450序列对于推进酶工程至关重要.
- 现有的方法在实现序列生成的多样性和准确性方面面临挑战.
研究的目的:
- 引入P450Diff2,一种用于生成人工细胞染色体P450酶序列的新型扩散模型.
- 在序列忠实性和多样性方面,评估P450Diff2的性能与以前的模型相比.
- 证明P450Diff2在新酶工程和功能序列生成方面的潜力.
主要方法:
- 开发了P450Diff2,这是一个基于EvoDiff-Seq框架 (6400万参数) 的扩散模型.
- 在来自不同数据库的100多万个非冗余P450蛋白序列的大数据集上训练了P450Diff2.
- 使用诸如氨基酸组成,特征空间覆盖,相似性配置和结构合理性 (pLDDT分数) 等指标评估生成的序列.
主要成果:
- 在多个评估指标中,P450Diff2的表现优于P450Diffusion模型.
- 生成的序列具有很高的结构可信性,平均pLDDT得分为72.29.
- 60%的生成序列正确折叠成生物活性P450酶,显示功能潜力.
结论:
- P450Diff2有效地生成具有高保真性和多样性的人工P450序列,并保留结构特征.
- 该模型显示了功能序列生成的强大潜力,加速了新的酶工程.
- 这种方法为快速酶设计提供了一个可扩展的范式,减少了实验验证的时间和成本.
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