Bioinformatics linkage of protein disorder and function

蛋白质紊乱与功能的生物信息学联系

• 批准号: 7034317
• 负责人: ALAN KEITH DUNKER
• 金额: $ 1.26万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7034317
• 关键词: Bioinformatics; linkage; protein; disorder; function

DESCRIPTION (provided by applicant): The overall goal is to understand the relationships between intrinsic disorder and protein function. Databases of ordered and disordered proteins provided the starting point for this work. Lack of acomplete annotation limited the previous research, so the first goal will be to exhaustively annotate the current databases of ordered and disordered protein. Even with the incomplete annotation, 28 functions from more than 100 disordered proteins have been identified. These functions fall into four categories: molecular recognition, protein modification, entropic chains, and molecular assembly and disassembly. Bioinformatics and datamining methods will be used to extend ourknowledge of the roles that intrinsic protein disorder plays in the first three of these four broad set of functions. 1. Molecular recognition: the hypothesis to be tested is that proteins involved in signal transduction and regulation commonly use intrinsic disorder in recognizing their binding targets. 2. Protein modification: the hypothesis to be tested is that chemical modification primarily involves residues that are located within intrinsically disordered regions possibly due to the requirement for disorder-to-order transitions upon binding to the modifying enzyme. Special emphasis will be placed on studying phosphorylation, but glycosylation, acetylation, ubiquitination, and other modifications,will be considered as time permits. 3. Entropic chains: the hypothesis to be tested is that alternative splicing in mRNAs occurs mostly in regions that code for disordered protein possibly because locating alternative splice sites in disordered regions circumvents the problems associated with locating alternative splice sites within structured protein. The proposed research has important implications for cancer research for, as will be shown, many cancer-associated proteins have large regions of putative intrinsic disorder.

描述（由申请人提供）： 总体目标是了解内在障碍和蛋白质功能之间的关系。有序和无序蛋白质的数据库为这项工作提供了起点。缺乏分解注释限制了先前的研究，因此第一个目标是详尽注释有序和无序蛋白质的当前数据库。即使有不完整的注释，已经确定了100多种无序蛋白质的28个功能。这些功能分为四类：分子识别，蛋白质修饰，熵链以及分子组装和拆卸。 生物信息学和数据安装方法将用于扩展我们对在这四个广泛的功能中的前三个中固有的蛋白质障碍在前三个功能中发挥作用的作用的知识。 1。分子识别：要检验的假设是，参与信号转导和调控的蛋白质通常在识别其结合靶标时通常使用固有疾病。 2.蛋白质修饰：要检验的假设是，化学修饰主要涉及位于本质上无序区域内的残基，这可能是由于对疾病到阶层与修饰酶结合时的要求造成的。将特别重点放在研究磷酸化上，但是将视为时间允许，将糖基化，乙酰化，泛素化和其他修饰视为。 3.熵链：要检验的假设是，mRNA中的替代剪接大部分发生在无序蛋白质编码的区域中，可能是因为在无序区域定位替代剪接位点避免了与在结构性蛋白质中找到替代剪接位点有关的问题。拟议的研究对癌症研究具有重要意义，如将表明的，许多与癌症相关的蛋白质具有较大的假定内在疾病区域。