CATALYTIC STRATEGIES OF CHOLINESTERASES & TRYPSIN MOLECULAR DYNAMICS STUDIES

在这个更新时期，我们将使用量子力学方法， 分子动力学模拟和自由能微扰方法， 继续探索结构与功能之间的关系， 两个家族的普遍存在的代谢血红素蛋白，过氧化物酶和 细胞色素P450 具体研究内容包括 (1)继续描述在转变的步骤， 将这些酶转化为它们的催化活性形式（2） 用于产物预测的底物酶复合物的研究 这两种血红素蛋白对特定底物的选择性 (3)阐明结合水、蛋白质结构和 调节酶中P450同工酶的特异性点突变 （4）结合相对自由能的计算 P450cam的抑制剂和（5）底物的表征 两种辣根过氧化物酶的结合位点

In this renewal period, we shall use quantum mechanical methods, molecular dynamics simulations and free energy perturbation methods to continue to probe the relationship between structure and function of two families of ubiquitous metabolizing heme proteins, peroxidases and the cytochrome P450s. The specific studies that will be made include (1) Continued characterization of the steps in the transformation of these enzymes to their catallytically active form (2) Continued Studies of Substrate enzyme complexes for prediction of product selectivity by specific substrates by these two types heme proteins (3) Elucidation of role of bound water, protein architecture and specific point mutations of P450 isozymes in modulating enzyme function; (4) Calculations of the relative free energies of binding inhibitors to P450cam and (5) Characterization of the substrate binding sites of two horseradish peroxidases