Structural Interpretation of the Protein Interactome

蛋白质相互作用组的结构解释

• 批准号: 1021785
• 负责人: Robert Jernigan
• 金额: $ 58.2万
• 依托单位: Iowa State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1021785&HistoricalAwards=false
• 关键词: Structural; Interpretation; Protein; Interactome

The large volume of data available for protein-protein interaction networks has not been fully comprehended or validated. This project will combine protein structural modeling with these data to significantly enhance their value, and to develop a deeper understanding of these data. The aim is to test the data and discover missing interactions, to develop molecular models of most pairs of interactions, and in this way to learn about the compatibilities of the pairs of interactions. The molecular modeling will rely on available protein structures, comparative modeling for those not available in the PDB and docking of the individual protein pairs using software presently provided by others. Physical overlaps in binding sites will be used to determine whether interaction sites overlap and are thus incompatible or whether they can coexist in assemblages of multiple proteins. Clustering the proteins for related functions is important to limit the number of combinations of interactions to be considered and will compensate for some uncertainties in the modeling. The overall objective is to fully investigate all pairs of interactions and their interdependences. Validation of some newly predicted interactions will be carried out by mass spectrometry. Higher order assemblages will be constructed that are consistent with the structural models of the binding sites, leading to structural assemblages for specific functions, on the same pathway. These analyses are important for investigating the details of functional clusters of proteins. In this project, all of the individual clusters will be investigated for their functional relationships, for their molecular structures, and as an important way to annotate the protein-protein interaction networks. Broader ImpactsThe protein-protein interaction annotation server will permit large numbers of users to access the whole body of information that will be generated during the project. Research-based graduate student training will be provided, and the student's educational experiences will be enhanced by this project. Native American, Hispanic and African-American students particularly will be sought for engagement in this project through collaborations at other Universities, having large populations of these students. All students for recruitment to this project will be targeted from these sources, enhancing the continuing search for more diverse future scientists from multiple programs and multiple institutions.

蛋白质-蛋白质相互作用网络的大量数据尚未得到充分理解或验证。该项目将联合收割机蛋白质结构建模与这些数据相结合，以显着提高其价值，并发展对这些数据的更深入的理解。目的是测试数据并发现缺失的相互作用，开发大多数相互作用对的分子模型，并以这种方式了解相互作用对的相容性。分子建模将依赖于可用的蛋白质结构，PDB中不可用的那些蛋白质结构的比较建模，以及使用目前由其他人提供的软件对单个蛋白质对进行对接。结合位点的物理重叠将用于确定相互作用位点是否重叠，从而不相容，或者它们是否可以共存于多种蛋白质的集合体中。对相关功能的蛋白质进行聚类对于限制要考虑的相互作用组合的数量是重要的，并且将补偿建模中的一些不确定性。总体目标是充分调查所有对的相互作用和它们的相互依赖性。一些新预测的相互作用的验证将通过质谱法进行。将构建与结合位点的结构模型一致的更高阶集合体，从而在相同途径上产生特定功能的结构集合体。这些分析对于研究蛋白质功能簇的细节非常重要。在这个项目中，将研究所有单个簇的功能关系，它们的分子结构，并作为注释蛋白质-蛋白质相互作用网络的重要方式。 更广泛的影响蛋白质相互作用注释服务器将允许大量用户访问项目期间生成的全部信息。 将提供以研究为基础的研究生培训，学生的教育经验将通过该项目得到加强。美洲原住民，西班牙裔和非洲裔美国学生，特别是将寻求通过在其他大学的合作，在这个项目的参与，这些学生的人口众多。该项目招募的所有学生都将从这些来源中挑选，从而加强对来自多个项目和多个机构的更多样化的未来科学家的持续寻找。