多维计算策略增强了α-galactosidase的热稳定性
Youfeng Zou1, Pu Zheng1, Pengcheng Chen1
1Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China.
International journal of biological macromolecules
|May 19, 2025
概括
蛋白质工程增强了阿斯伯吉路斯管道菌的热稳定性和催化效率alpha-galactosidase (AtWU_04653). 计算设计策略显著提高了酶的性能,减少了工业应用的实验选.
科学领域:
- 酶学和蛋白质工程 酶学和蛋白质工程
- 计算生物学和生物信息学
背景情况:
- 微生物α-galactosidases在工业上有价值,但受到热不稳定的影响.
- 在苛刻的应用中,蛋白质工程对于提高酶性能至关重要.
研究的目的:
- 通过使用双计算策略,提高阿斯伯吉路斯管道菌的热稳定性和催化效率 (AtWU_04653).
- 为高效的酶设计和优化提供框架.
主要方法:
- 战略I:用于图书馆建设的综合计算设计 (ABACUS2/PROSS/DBD2).
- 战略II:基于物理的计算方法,包括GROMACS分子动力学模拟,罗塞塔展开的自由能量计算和SPIRED机器学习预测.
- 使用了序列保存分析和展开的自由能量计算.
主要成果:
- 突变A169P (战略I) 的热半衰期增加了78.52%,催化效率提高了52.04%.
- 稳定变种E429I,N380L和T64P (战略II) 的延长半衰期分别为57.33%,67.17%和41.34%.
- 变种E429I和T64P也显示了显著的催化活性增强 (85.25%和65.90%).
结论:
- 双计算策略有效地提高了酶的热稳定性和催化活性.
- 开发的框架减少了实验选,使协同优化成为可能.
- 这项研究为计算酶设计和功能优化提供了有价值的技术参考.
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