Understanding structural flexibility and evolutionary divergence of proteins

了解蛋白质的结构灵活性和进化分歧

• 批准号: 9276056
• 负责人: Adam Godzik
• 金额: $ 42.84万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9276056
• 关键词: Applications Grants; Biology; Cell physiology; Disease; Drug resistance; Elements; Evolution; Goals; Grant; Group Structure; Individual; Malignant Neoplasms; Molecular; Mutate; Mutation; Organism; Pattern; Pharmaceutical Preparations; Protein Family; Proteins; Structure; Time; Work; flexibility; implementation research; insight; pathogen; protein structure; public health relevance; response; tool

 DESCRIPTION (provided by applicant): In biology, understanding the past can give us insights to better understand the present. The goal of the work proposed in this grant application is to develop integrated sequence, function, and structure approaches to study evolution of all three aspects of individual proteins and the networks they form. Unique tools for protein structure alignment and comparison developed in our group allow us not only to identify common structural elements of pairs and groups of structures, but also to describe and classify differences in the structures. Such analyses can provide us with insights not only into the function-related structural rearrangements, but also into evolutionary changes in the sequence caused by evolutionary drift or function-driven changes. At the same time, analysis of the evolution of protein networks can give us synergistic insights into evolution of functions of the same proteins. In this grant we propose to expand such analyses and integrate them across all three aspects with the help and new tools for such analyses we are planning to develop. Understanding of molecular details of the evolution of protein families, such as identification of regions that are strongly conserved in evolution versus malleable regions undergoing extensive changes with no effect on the function or identification of new functional regions emerging at specific moments in evolution, can give us insights into evolution of various cellular processes. At the same time, such analyses can help us answer practical questions such as effects of disease mutations or responses to drugs.

 描述（由申请人提供）：在生物学中，了解过去可以让我们更好地了解现在。这项研究的目标是开发整合的序列、功能和结构方法，以研究单个蛋白质及其形成的网络的所有三个方面的进化。我们小组开发的蛋白质结构比对和比较的独特工具不仅使我们能够识别结构对和结构组的共同结构元素，而且还可以描述和分类结构中的差异。这种分析不仅可以为我们提供与功能相关的结构重排的见解，而且还可以为我们提供由进化漂移或功能驱动的变化引起的序列的进化变化。与此同时，对蛋白质网络进化的分析可以为我们提供对相同蛋白质功能进化的协同见解。在这笔赠款中，我们建议扩大此类分析，并在我们计划开发的此类分析的帮助和新工具的帮助下，将其整合到所有三个方面。了解蛋白质家族进化的分子细节，例如识别在进化中高度保守的区域与经历广泛变化而对功能没有影响的可延展区域，或者识别在进化中特定时刻出现的新功能区域，可以让我们深入了解各种细胞过程的进化。与此同时，这种分析可以帮助我们回答一些实际问题，例如疾病突变的影响或对药物的反应。