Conformationally Dynamics in Biomolecule function

生物分子功能中的构象动力学

• 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

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.

我们是西蒙弗雷泽大学一个专注于生物化学的年轻研究小组。 我们计划的总体目标是了解，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”）与这些分子识别其配体的能力联系起来，并了解动力学的差异如何产生不同的功能。 这些目标对于我们对以下系统的机制理解和最终靶向研究具有重要意义：1）隐花色素和光解酶，一对结构同源但功能不同的蛋白质。 光解酶是DNA修复酶，其通过从DNA双链体翻转受损碱基来发挥功能，而隐花色素在人类生理学中具有重要但知之甚少的功能，但不能进行这种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。 我们的目标也具有更广泛的意义，因为我们预测，机械论的洞察力将是普遍的。 因此，通过这些研究，我们希望更好地了解蛋白质和核酸如何使用序列依赖性环动力学来编码配体特异性和功能特异性构象之间的交换。