REFINEMENT OF FOLDED PROTEIN STRUCTURES

在加州大学旧金山分校的Dill团队的合作下，我正在致力于 小分子蛋白质(&lt；100)的从头算蛋白质结构预测 氨基酸)，如CMTI和内皮素。从最低处开始 我们合作者折叠的解析终点结构 算法，我使用分子动力学来执行高分辨率 构象采样寻找天然结构，这是我们 预计将处于我们力场的全局最小值。虽然 同源建模和线程被认为是成功的 未来十年内的总体折叠预测，尽管 折叠算法显示出的前景，这些技术显然缺乏 在分子水平上有足够的细节，以使结构 预测具有重大的实际应用价值。值得关注的是 捆绑口袋和活动场所，在那里小型结构 差异会导致蛋白质活性的显著变化。给出了一个 成功的两步法，准确地确定了宏观和 蛋白质的微观结构，制药业将 在其生产治疗药物的努力中受益匪浅 是改变蛋白质活性所必需的。计算机图形学 实验室已被证明是一个宝贵的工具，使我能够更好地 分析我的数据。我经常使用可视化软件包 MidasPlus查看我的蛋白质结构。我还使用了 用于运行其他应用程序的硬件，这些应用程序显示我的 动力学模拟。CGL工作人员也是一个有用的资源 凭借他们的编程专业知识。

In a collaboration with the Dill group at UCSF, I am working on the ab initio protein structure prediction of small proteins (< 100 amino acids) such as CMTI and endothelin. Starting with the low resolution end point structure of our collaborators' folding algorithms, I use molecular dynamics to perform high resolution conformational sampling in search of the native structure, which we predict to be at the global minimum of our force field. Although homology modelling and threading are postulated to be successful in overall fold prediction within the next decade, and despite the great promise shown by folding algorithms, these techniques clearly lack sufficient detail at the molecular level that will allow structure prediction to have significant practical application. Of interest are the b inding pockets and active sites, where small structural differences lead to notable change in protein activity. Given a successful two-step method that accurately determines the macro- and microscopic structures of proteins, the pharmaceutical industry will benefit tremendously in its efforts to produce therapeutic drugs that are needed to modify protein activity. The Computer Graphics Laboratory has proven to be a valuable tool in enabling me to better analyze my data. I frequently use the visualization software package MidasPlus to look at my protein structures. I have also used the hardware to run other applications that display the trajectories of my dynamics simulations. The CGL staff is a helpful resource as well with their programming expertise.