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

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