Deuteron Nuclear Magnetic Resonance Studies of Oriented Proteins and Model Compou

定向蛋白质和模型化合物的氘核磁共振研究

• 批准号: 8582410
• 负责人: Robert L. Vold
• 金额: $ 6.75万
• 依托单位: COLLEGE OF WILLIAM AND MARY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8582410
• 关键词: Accounting; Address; Alaska; Alzheimer' s Disease; Amino Acids; Behavior; Binding Proteins; Biological Models; Catalysis; Chickens; Collaborations; Complex; Computer Analysis; Computer software; Computers; Coupled; Data; Drug Formulations; Environment; Enzymes; Equation; Familiarity; Goals; Investigation; Lead; Least-Squares Analysis; Measurement; Membrane; Methodology; Microscopic; Modeling; Molecular; Morphologic artifacts; Motion; Motivation; Neurodegenerative Disorders; Nuclear Magnetic Resonance; Parkinson Disease; Pathway interactions; Physiologic pulse; Plant Roots; Potential Energy; Procedures; Process; Proteins; Public Domains; Relaxation; Reporting; Resolution; Retinal Cone; Shapes; Side; Site; Solid; Solutions; Spin Labels; System; Techniques; Technology; Temperature; Testing; Time; To specify; Universities; Vertebral column; aqueous; base; design; deuteron; globular protein; graphical user interface; improved; interest; liquid crystal; macromolecule; magnetic field; molecular dynamics; molecular recognition; protein folding; quantum; research study; simulation; single bond; small molecule; solid state; solid state nuclear magnetic resonance; tool; villin

DESCRIPTION (provided by applicant): This is a proposal to adapt techniques developed for solid state deuteron nuclear magnetic resonance (NMR) to quantitative investigations of molecular dynamics in oriented systems of model compounds and small proteins. This includes developing and testing new pulse sequences to improve site-specific spectral resolution, designing realistic, new motional models that account for correlated motions, and providing well documented, easy to use software for analysis of biomolecular motion in general. Even though most biologically significant motions (e.g., enzyme catalysis, molecular recognition, etc.) occur near room temperature in aqueous solutions, there are compelling reasons for the current intense interest in solid state NMR methodology for studying biodynamics. One motivation is the fact that local, internal motions in large biomolecules are surely relevant to their function, but are difficult to study by solution state NMR due to interference from slow overall tumbling of the whole molecule. A second motivation is that accurate determination of the activation energies for different motional processes, which can provide useful information about minimum energy pathways through the complex potential energy landscape of a folding protein, typically requires measurements over a wide range of temperatures not accessible with aqueous solutions. A third motivation is that the motional time scales relevant for motion of proteins and small molecules in oriented membranes are often too long to be investigated by full molecular dynamic simulations, but are readily accessible to simulation suitably adapted models commonly used to describe motion in solids. Recent advances in computer technology permit simulations of NMR line shapes and spin relaxation behavior to be carried out using complex motional models that only a few years ago would have been deemed too computationally expensive. One problem with such models is their large number of adjustable parameters: few studies have been reported that assess in a systematic manner which parameters in a given model can be determined reliably from what kinds of experimental NMR data. A second problem is that designing a complex model requires significant familiarity on the part of the designer with intricate mathematical procedures for solving large sets of coupled differential equations. The graphical user interface described in this proposal addresses both these problems by providing users with advanced statistical tools for assessing parameter reliability, and allowing the user wherever possible to specify motional trajectories and rates in chemically intuitive terms. Thus, it will greatly facilitate the ability of non-specialists in solid state NMR to exploit this important technique.

描述（由申请人提供）：这是一项建议，以适应用于固态Deuteron核磁共振（NMR）开发的技术，以定量研究模型化合物和小蛋白质的定向系统中的分子动力学。这包括开发和测试新的脉冲序列，以改善位点特异性光谱分辨率，设计逼真的，新的运动模型，以说明相关运动，并提供易于记录，易于使用的软件，以分析一般的生物分子运动。 即使在水溶液中，大多数具有生物学意义的运动（例如酶催化，分子识别等）发生在室温附近，但仍有令人信服的原因引起了目前对研究生物动力学的固态NMR方法的强烈兴趣。一个动机是，大型生物分子中的局部内部运动肯定与它们的功能有关，但是由于整个分子的整体逐渐滚动而干扰了溶液状态NMR，因此很难通过溶液状态NMR进行研究。第二个动机是，通过折叠蛋白的复杂势能景观提供有关不同运动过程的激活能的准确确定，这可以提供有关最小能量途径的有用信息，通常需要在无法使用水溶液的广泛温度下进行测量。第三个动机是，与蛋白质和定向膜中小分子运动相关的运动时间尺度通常太长而无法通过完整的分子动力学模拟来研究，但很容易访问适当适当适合描述固体运动运动的模拟模型。 计算机技术的最新进展允许使用复杂的运动模型对NMR线形状和自旋松弛行为进行模拟，而该模型仅在几年前才被认为是计算上太昂贵的。此类模型的一个问题是它们的大量可调节参数：很少有研究报告以系统的方式评估给定模型中哪些参数可以从哪些类型的实验性NMR数据可靠地确定。第二个问题是，设计复杂的模型需要设计人员的重要熟悉度，并使用复杂的数学程序来求解大量的耦合微分方程。此提案中描述的图形用户界面通过为用户提供评估参数可靠性的高级统计工具，并允许用户以化学直观的术语指定运动轨迹和速率，从而解决了这两个问题。因此，它将极大地促进固态NMR中非专家利用这一重要技术的能力。

项目成果

Glassy dynamics of protein methyl groups revealed by deuteron NMR.

氘核核磁共振揭示蛋白质甲基的玻璃态动力学。

• DOI: 10.1021/jp311112j
• 发表时间: 2013
• 期刊: The journal of physical chemistry. B
• 作者: Vugmeyster,Liliya;Ostrovsky,Dmitry;Penland,Kirsten;Hoatson,GinaL;Vold,RobertL
• 通讯作者: Vold,RobertL