ENZYME SPECIFICITY USING NORMAL MODE ANALYSIS

使用正态模式分析的酶特异性

• 批准号: 6280169
• 负责人: DAVID W MILLER
• 金额: $ 0.31万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6280169
• 关键词: biomedical resource; model design /development; proteins; technology /technique

We calculate normal modes of alpha-lytic protease, both for the wild type and for the M190A mutant, in order to investigate how internal vibrations in the enzyme might contribute to a characteristic feature of its catalytic specificity. While the wild type is highly specific for small substrates in its primary specificity pocket, the M190A mutant has a much broader specificity, catalyzing both large and small substrates. We hypothesize that for the atoms lining the walls of the specificity pocket, the wild-type normal modes have a more symmetric character, with the walls vibrating in phase, and the size of the pocket remaining relatively fixed. This is in agreement with previous X-ray crystallographic results. In contrast, we expect that the mutant modes have a more antiymmetric character, with the walls vibrating out of phase, and the pocket able to expand and contract. These results would suggest that the internal vibrations of a molecule may play a role in determining both binding and catalytic specificity. The use of resources has been very important for the detailed graphical analyses of our normal-mode results. An example of the types of calculations we make is that of the changes in active-site volume and surface area that take place as the protein structure is perturbed along each of its normal modes. These computationally-intensive calculations are made using an algorithm included in the Computer Graphics Labroatory's MidasPlus package. In addition to such calculations, we have used the CGL extensively for detailed three-dimensional rendering of both our crystallographic and modeled protein structures.

我们计算了α-裂解酶的正常模式，这两种模式都是 野生型和M190A突变体，以便研究 酶的内部振动可能会导致一种特征 它的催化专一性。而野生型的高度 对于其主要专一性口袋中的小底物， M190A突变体具有更广泛的特异性，既催化大分子和 小衬底。我们假设，对于排列在墙上的原子 在特异性口袋中，野生型正常模式有更多的 对称特征，墙壁同步振动，大小 口袋的位置保持相对固定。这一点与 先前的X射线结晶学结果。相比之下，我们预计 突变模式具有更反对称的特征，因为墙 异相振动，口袋能够膨胀和收缩。 这些结果表明，分子的内部振动 可能在决定结合和催化专一性方面发挥作用。 资源的使用一直是非常重要的详细 对我们的正常模式结果进行图形分析。这是一个示例 我们进行的计算类型是活动站点中的更改类型 当蛋白质结构发生时，体积和表面积 沿着它的每一种正常模式扰动。这些 使用一种算法进行计算密集型计算 包括在计算机图形实验室的MidasPlus包中。在……里面 除了这样的计算外，我们还广泛地使用CGL来 详细的三维渲染我们的结晶学和 模拟蛋白质结构。