Conformationally Dynamics in Biomolecule function

生物分子功能中的构象动力学

基本信息

批准号：
312645-2008
负责人：
ONeill, Melanie
金额：
$ 2.99万
依托单位：
Simon Fraser University
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2010
资助国家：
加拿大
起止时间：
2010-01-01 至 2011-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=457521
关键词：
Conformationally Dynamics Biomolecule function

项目摘要

We are a young research group focused on biological chemistry at Simon Fraser University. The overall aim of our program is to understand, predict, and control how the structure and dynamics of biological molecules govern their function. The focus of the proposed research is to link motion ("conformational dynamics") of unstructured loops in proteins and nucleic acids to the ability of these molecules to recognize their ligands, and to understand how differences in dynamics engender divergent function. These aims are significant to our mechanistic understanding and eventual targeting of the following systems proposed for investigation: 1) Cryptochromes and photolyases, a pair of structurally homologous but functionally divergent proteins. Photolyases are DNA repair enzyme that function by flipping damaged bases from the DNA duplex, while cryptochromes have essential, yet poorly understood, functions in human physiology, but are incapable of carrying out this DNA repair. 2) Riboswitches, recently discovered RNA molecules capable of turning genes on and off in response to binding of small molecules. Our aims are also more broadly significant because we predict that the mechanistic insight will be general. Thus, with these investigations we hope to better understand how proteins and nucleic acids use sequence-dependent loop dynamics to encode ligand specificity and exchange amongst functionally-specific conformations.

我们是一个年轻的研究小组，专注于西蒙·弗雷泽大学（Simon Fraser University）的生物学化学。我们计划的总体目的是了解，预测和控制生物分子的结构和动力学如何控制其功能。拟议的研究的重点是将蛋白质和核酸中非结构化环的运动（“构象动力学”）联系起来，将这些分子识别其配体识别其配体的能力，并了解动力学的差异如何引起发散功能。这些目的对于我们的机械理解和最终靶向以下提出的研究系统至关重要：1）加密斑块和光溶解酶，这是一对在结构上同源但功能上不同的蛋白质。光溶解酶是通过翻转DNA双链体受损碱基的DNA修复酶的作用，而密码染色体在人类生理学中具有必不可少的但知之甚少的功能，但无法进行此DNA修复。 2）核糖开关，最近发现的RNA分子能够响应小分子的结合而打开和关闭基因。我们的目标也更加广泛，因为我们预测机械洞察力将是一般的。因此，通过这些研究，我们希望更好地理解蛋白质和核酸如何使用序列依赖性环动力学来编码功能特定的构象之间的配体特异性和交换。