Determining Structural Ensembles for Intrinsically Unstructured Proteins

确定本质上非结构化蛋白质的结构整体

• 批准号: 0744839
• 负责人: Gary Daughdrill
• 金额: $ 57.89万
• 依托单位: Regents of the University of Idaho
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2009-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0744839&HistoricalAwards=false
• 关键词: Determining; Structural; Ensembles; Intrinsically; Unstructured

The objective of this project to is study structural variations in a family of intrinsically unstructured proteins (IUP). Based on the PI's previous work, and the work of others, it is now clear that IUPs form a diverse set of protein families that can elicit biological function using a variety of mechanisms. This project has two aims: (I) Determine structural ensembles for a set of homologous proteins that are intrinsically unstructured. In this specific aim, paramagnetic relaxation enhancement will be used to estimate long-range interatomic distances that can be used to restrain structure calculations. The structural ensembles will then be validated using residual dipolar couplings and small angle x-ray scattering. (II) Determine the relationship between sequence identity and structural similarity for a set of homologous proteins that are intrinsically unstructured. In this specific aim, eigenvector decomposition of protein contact maps will be used to identify similarities between the structural ensembles. This data will then be correlated with genetic distance matrices to determine the percent sequence identity necessary for structural similarity. Experiments in this specific aim will also test the importance of amino acid composition for specifying the structural ensemble. Successful completion of both specific aims will facilitate the development of models of protein evolution for intrinsically unstructured proteins that can be used to estimate their dynamic structures based on sequence identity. The PI has a strong record of advancing discovery and understanding while promoting teaching, training, and learning. This is evidenced by the three peer reviewed publications that have undergraduate students as authors and five peer reviewed publications that have authors from underrepresented groups. The PI is also very committed in disseminating scientific information to general public. In the summer of 2004, the PI participated in a state funded workshop for secondary education to science teachers. The PI gave lectures on the general principles of protein structure and function as well as a tutorial for using molecular graphics programs in the classroom. This project will involve two undergraduate students and a female research technician and the PI will continue his efforts to involve science teachers in basic scientific research by holding an annual workshop whose purpose would be to introduce science teachers to the latest breakthroughs and make them aware of new web-based tools for scientific discovery.

该项目的目标是研究本质上非结构化蛋白质 (IUP) 家族的结构变异。根据 PI 之前的工作以及其他人的工作，现在很清楚 IUP 形成了一组多样化的蛋白质家族，可以利用多种机制引发生物学功能。该项目有两个目标：（I）确定一组本质上非结构化的同源蛋白质的结构整体。在这个具体目标中，顺磁弛豫增强将用于估计可用于限制结构计算的长程原子间距离。然后，将使用残余偶极耦合和小角度 X 射线散射来验证结构整体。 (II) 确定一组本质上非结构化的同源蛋白质的序列同一性和结构相似性之间的关系。在这个特定目标中，蛋白质接触图的特征向量分解将用于识别结构整体之间的相似性。然后将该数据与遗传距离矩阵相关联，以确定结构相似性所需的序列同一性百分比。这一特定目标的实验还将测试氨基酸组成对于指定结构整体的重要性。这两个具体目标的成功完成将促进本质上非结构化蛋白质的蛋白质进化模型的开发，该模型可用于根据序列同一性估计其动态结构。 PI 在推动发现和理解、同时促进教学、培训和学习方面有着良好的记录。三份由本科生作为作者的同行评审出版物和五份由来自代表性不足群体的作者组成的同行评审出版物就证明了这一点。 PI 还非常致力于向公众传播科学信息。 2004 年夏天，PI 参加了国家资助的中等教育科学教师讲习班。 PI 就蛋白质结构和功能的一般原理进行了讲座，并提供了在课堂上使用分子图形程序的教程。该项目将涉及两名本科生和一名女性研究技术员，PI 将继续努力通过举办年度研讨会，让科学教师参与基础科学研究，其目的是向科学教师介绍最新的突破，并让他们了解新的知识。基于网络的科学发现工具。