CATALYTIC STRATEGIES OF CHOLINESTERASES & TRYPSIN MOLECULAR DYNAMICS STUDIES

在这个更新期，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 两个普遍存在的代谢血红素的蛋白质家族，过氧化物酶和 细胞色素P450s。将进行的具体研究包括 (1)继续描述转型中的步骤 这些酶的催化活性形式(2)继续 底物酶复合体预测产物的研究 这两种血红素蛋白对特定底物的选择性 (3)阐明结合水的作用、蛋白质结构和 调节酶P450同工酶的特异点突变 函数；(4)结合相对自由能的计算 P450cam抑制剂及(5)底物表征 两种辣根过氧化物酶的结合部位

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