Abstract: Lipase is a significant biocatalyst，because of its wide source and excellent catalytic activity and specificity in a great many reactions in water and even non-aqueous media. The research on catalytic mechanism and structure-function relationship of lipase becomes a hot point. Molecular simulation based on modern computer technology plays an increasingly important role in this area. In the paper，three stages of development and application of computer-aided molecular simulation on the research of properties and catalytic mechanism of lipases is reviewed. In the early stage，conformational changes of lipases were studied mainly by molecular dynamics. Flexible docking technology，which was developed afterwards，was mainly adopted to predict enantioselectivity and investigate the simplified catalytic mechanisms. Currently，more accurate molecular dynamics and QM/MM become the common research method for catalytic mechanism of lipase. By summarizing the development of computer-aided molecular simulation，together with the comparison of the three stages，it could be inferred that in the foreseeable future，the molecular simulation technology will play more and more important role in the research of properties and catalytic mechanism of enzymes. The comprehensive application of multiple simulation method and the fast maturity of ab initio calculation must also play irreplaceable role in the understanding of structure-activity relationship of protein.

Key words: molecular simulation, molecular dynamics, molecular docking, QM/MM, QSAR, lipase

摘要： 脂肪酶是一种重要的生物催化剂，其来源广泛，可在水相甚至非水介质中催化多种反应，并表现出很高的立体选择性和催化活性。有关脂肪酶的应用和基础研究备受重视，特别是脂肪酶催化机理和结构功能关系成为近年来研究热点，基于现代计算机技术的分子模拟计算在相关研究中扮演着越来越重要的角色。本文综述了计算机辅助分子模拟技术应用于脂肪酶性质及催化机理研究领域的3个发展阶段：早期的分子动力学模拟主要用于脂肪酶构象变化的研究；随后出现的柔性分子对接技术则可研究和预测脂肪酶的对映体选择性及简单的催化机理；近年来发展的运算时间更长的分子动力学和量子力学/分子力学（QM/MM）方法则可全面研究脂肪酶的酶学性质及催化机理。通过对上述技术发展的回顾与对比分析可以预见，分子模拟手段将在酶的性质及酶催化机理研究领域发挥更为重要的作用，并且多种模拟技术的综合应用和从头计算分子模拟技术的日益成熟，将为人们更加深入地认识蛋白质构效关系发挥不可替代的作用。

关键词: 分子模拟, 分子动力学, 分子对接, 量子力学/分子力学, 定量构效关系, 脂肪酶