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）：这是一项将固态氘核磁共振（NMR）技术用于定量研究模型化合物和小蛋白质定向系统中分子动力学的建议。这包括开发和测试新的脉冲序列，以提高特定地点的光谱分辨率，设计现实的，新的运动模型，占相关的运动，并提供良好的记录，易于使用的软件分析生物分子的运动一般。 尽管大多数生物学上重要的运动（例如，酶催化、分子识别等）在室温附近的水溶液中发生，有令人信服的理由，目前强烈的兴趣，固态核磁共振方法研究生物动力学。一个动机是大生物分子中的局部内部运动肯定与它们的功能相关，但由于整个分子缓慢的整体翻滚的干扰，很难通过溶液状态NMR进行研究。第二个动机是，准确测定不同运动过程的活化能，这可以提供有关折叠蛋白质复杂势能景观的最小能量途径的有用信息，通常需要在水溶液无法达到的宽温度范围内进行测量。第三个动机是，与定向膜中蛋白质和小分子运动相关的运动时间尺度通常太长，无法通过全分子动力学模拟进行研究，但可以很容易地模拟通常用于描述固体运动的适当适应模型。 计算机技术的最新进展允许使用复杂的运动模型来进行NMR线形状和自旋弛豫行为的模拟，仅在几年前，这些模型还被认为在计算上过于昂贵。这种模型的一个问题是它们的大量可调参数：很少有研究报告，评估在一个系统的方式，在一个给定的模型中的参数可以可靠地确定从什么样的实验NMR数据。第二个问题是，设计一个复杂的模型需要设计者非常熟悉复杂的数学程序，以解决大量的耦合微分方程。本提案中描述的图形用户界面通过为用户提供用于评估参数可靠性的高级统计工具来解决这些问题，并允许用户尽可能以化学直观的术语指定运动轨迹和速率。因此，这将极大地提高固态核磁共振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