中文摘要
酶的三维结构及其催化反应机理研究是目前理论化学的前沿研究领域之一。本项目利用分子力学、分子动力学及量子化学计算方法，对细胞色素P450酶、水解酶等几类重要酶的三维结构及催化反应机理进行理论研究。通过同源模建和分子力学优化及分子动力学模拟，结合相关实验数据，得到了可靠的酶的三维结构。对三维结构表面性质进行分析，确定了酶的活性位点的构型和氨基酸组成，并进行了底物分子与底酶的对接。根据底物分子与活性位点中氨基酸的互相作用能指认出活性位点中起重要催化作用的氨基酸。在此基础上，建立理论化学计算模型，通过量子化学计算并与相关的酶催化活性实验相结合，探索酶催化反应机理，得到了变体酶结构与催化活性之间的一些关系，为深入了解变体酶的结构与生物功能的关系，寻求具有特定生物功能的新变体酶提供了可靠的理论依据。本项目共发表论文18 篇，其中17篇为SCI 杂志，1篇为国内核心期刊。
英文摘要
The study of the 3D structure and catalytic reaction mechanism of enzymes is a very active research field. The aim of this project is that by means of the theoretical chemistry calculation methods, the 3D structure and the catalytic reaction mechanism have been investigated for some kinds of important enzymes such as P450 mutase and hydrolase etc. The homology modeling, MM optimization, MD simulation and the corresponding experimental data are used to obtain the reliable 3D structures for the studied enzymes. By determining the configurations and component of amino acids in the active site, the docking study of ligand to the receptor is carried out to identify the amino acids in the active site which play important role for the catalytic reactions. On the base of the results obtained above, we set up the reasonable quantum chemical calculation model. Furthermore, by comparing the theoretical computational results with the corresponding experimental date about the catalytic activity, the catalytic reaction mechanism and relation between the structure of mutant enzyme and catalytic activity have been revealed. The theoretical results obtained from this project provide the basis for searching and designing new mutase which will have special biological function..In this project, 18 papers have been published in which 17 papers published in SCI journal.
结题摘要
酶的三维结构及其催化反应机理研究是目前理论化学的前沿研究领域之一。本项目利用分子力学、分子动力学及量子化学计算方法，对细胞色素P450酶、水解酶等几类重要酶的三维结构及催化反应机理进行理论研究。通过同源模建和分子力学优化及分子动力学模拟，结合相关实验数据，得到了可靠的酶的三维结构。对三维结构表面性质进行分析，确定了酶的活性位点的构型和氨基酸组成，并进行了底物分子与底酶的对接。根据底物分子与活性位点中氨基酸的互相作用能指认出活性位点中起重要催化作用的氨基酸。在此基础上，建立理论化学计算模型，通过量子化学计算并与相关的酶催化活性实验相结合，探索酶催化反应机理，得到了变体酶结构与催化活性之间的一些关系，为深入了解变体酶的结构与生物功能的关系，寻求具有特定生物功能的新变体酶提供了可靠的理论依据。本项目共发表论文18 篇，其中17篇为SCI 杂志，1篇为国内核心期刊。