Bioinformatics linkage of protein disorder and function

描述（由申请人提供）： 总体目标是了解内在障碍与蛋白质功能之间的关系。有序和无序蛋白质数据库为这项工作提供了起点。缺乏完整的注释限制了以前的研究，因此，第一个目标将是详尽地注释现有的有序和无序蛋白质数据库。即使在不完整的注释下，已经从100多个无序蛋白质中鉴定出28个功能。这些功能分为四类：分子识别，蛋白质修饰，熵链，分子组装和拆卸。 生物信息学和数据挖掘方法将用于扩展我们对内在蛋白质紊乱在这四大功能中的前三个中所起作用的认识。1.分子识别：待检验的假设是，参与信号转导和调节的蛋白质通常利用内在紊乱来识别它们的结合靶。2.蛋白质修饰：待检验的假设是化学修饰主要涉及位于固有无序区域内的残基，这可能是由于在与修饰酶结合时需要无序到有序的转变。重点将放在研究磷酸化，但糖基化，乙酰化，泛素化，和其他修饰，将被视为时间允许。3.熵链：待检验的假设是mRNA中的选择性剪接主要发生在编码无序蛋白质的区域中，这可能是因为在无序区域中定位选择性剪接位点避免了与在结构化蛋白质中定位选择性剪接位点相关的问题。这项研究对癌症研究具有重要意义，因为许多癌症相关蛋白质具有大面积的假定内在紊乱区域。

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.