计算机辅助糖苷酶分子设计与改造研究进展

糖苷酶作为一种重要的生物催化剂，在工业生物催化领域有着广阔的应用前景。但天然糖苷酶存在催化活性低、热稳定性和底物选择性差等缺点，严重限制了它在规模化生产中的推广应用。近年，有关糖苷酶催化机制与结构功能关系的研究备受关注，特别是计算机辅助酶设计在相关研究领域发挥着越来越重要的作用。本文综述了糖苷酶分子设计改造过程中应用的计算机辅助方法：包括同源比对、分子对接以及动力学模拟；系统阐述了这些计算方法在糖苷酶的结构与功能关系解析、酶催化分子机制、酶催化性能改造方面的应用现状。通过对上述方法的深入分析可以预见，计算机辅助方法将成为糖苷酶分子设计改造的重要手段，并且开发智能精准的计算分析方法将成为加快酶分子定向改造的新发展趋势。

Recent Progress in Computer-aided Design and Engineering of Glycosidases

Glycosidase is a significant biocatalyst to produce high value chemicals for promising industrial and biotechnological applications. However, there are still many problems in large-scale application of the natural glycosidases, such as low catalytic activity, poor thermostability and substrate selectivity. In recent years, the research on catalytic mechanism and structure-function relationship of glycosidase becomes a hot topic. The utilization of in silico techniques to aid enzyme design and modification are creating new opportunities for enzyme engineering. In the paper, commonly used in silico methods such as homology alignment, molecular docking and molecular dynamics simulation are reviewed. The different roles that in silico methods play in related research of glycosidases are systematically summarized, including understanding the relationship between structure and function of glycosidases, investigating catalytic processes and catalytic mechanisms, as well as designing and engineering glycosidases for improving performance. Through in-depth analysis of the above methods, it is foreseeable that computer-aided methods will become an important means of glycosidase molecule design and engineering. This paper also prospects that the development of intelligent and accurate in silico methods will become a new trend to accelerate the directed evolution of enzyme molecules.