Motional Modeling by NMR Relaxation

通过 NMR 松弛进行运动建模

• 批准号: 9814431
• 负责人: Erik Zuiderweg
• 金额: $ 35.4万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9814431&HistoricalAwards=false
• 关键词: Motional; Modeling; NMR; Relaxation

Understanding of protein function can only approach completeness if structure, interactions and local dynamics are understood in detail. In the past funding period, the foundation to experimentally derived motional models for fast local dynamics in protein modules has been established. The goal was to not only detect the existence of local dynamics but also describe what the motions actually are. this is achieved by measuring the NMR relaxation behavior for several nuclei associated with a single motion unit. This data is interpreted in terms of dynamical parameters for the different magnetic interaction vectors associated with the relaxation, from which a motional model can be developed. In the present work this new paradigm will be extended and refined with new NMR techniques for the description of local anisotropic dynamics of the protein backbone. Protein sidechains dynamics modeling will be approached in a similar way by measuring dynamical parameters for several different sidechain interaction vectors. The methods for the measurements of sloe conformational change dynamics will be improved. These dynamics are often associated with ligand/substrate interaction. By combination of several methods, structural as well dynamical, one can obtain models for the slow motions. The methods will be developed with and applied to the active site dynamics of a small ribonuclease and of a flavoprotein. In favorable cases the new methods can differentiate between correlated and uncorrelated local motions.Biological molecules such as proteins, DNA and RNA are essential to life. In order to understand how they function, many of these molecules have been analyzed in terms to their static structures in the recent decades. While this has yeilded much insight into function in qualitative terms, explanations in quantitative terms have remained elusive. Most biological molecules can be seen as engines or factories. Just as real engines ot factories only work when they are in motion, biobolecules have to move to carry out their functions. Thus, knowledge of how biomolecules actually work can only be complete when their dynamical aspects are studied in addition to static pictures. This porject will study the molecules in terms of their small-scale motions and will focus especially on dynamics of the active sites of enzymes. The resulting knowledge will contribute to the basic understanding of life-processes. For this research the technique of nuclear magnetic resonance at the highest possible magnetic field strengths will be used.

只有在结构、相互作用和局部动力学被详细理解的情况下，对蛋白质功能的理解才能接近完整。 在过去的资助期内，蛋白质模块中快速局部动力学的实验推导运动模型的基础已经建立。 目标不仅是检测局部动力学的存在，而且还要描述运动的实际情况。 这是通过测量与单个运动单元相关的几个核的NMR弛豫行为来实现的。 这些数据被解释为与弛豫相关的不同磁相互作用矢量的动力学参数，从中可以开发一个运动模型。 在目前的工作中，这一新的范例将扩展和完善与新的NMR技术的局部各向异性动力学的蛋白质骨架的描述。 蛋白质侧链动力学建模将以类似的方式通过测量几个不同的侧链相互作用矢量的动力学参数来进行。 同时也将进一步完善黑刺李构象变化动力学的测定方法。 这些动力学通常与配体/底物相互作用有关。 通过几种方法的结合，结构以及动力学，可以获得模型的慢动作。 该方法将开发和应用到一个小的核糖核酸酶和黄素蛋白的活性位点动力学。 在有利的情况下，新的方法可以区分相关和不相关的局部运动。生物分子，如蛋白质，DNA和RNA是生命所必需的。 为了了解它们的功能，近几十年来，人们已经分析了其中许多分子的静态结构。 虽然这在定性方面对功能有了很大的了解，但定量方面的解释仍然难以捉摸。 大多数生物分子可以被看作是发动机或工厂。 就像工厂里的真实的发动机只有在运转时才能工作一样，生物分子也必须运动才能发挥作用。 因此，只有在静态图像之外研究生物分子的动力学方面，才能完整地了解生物分子实际上是如何工作的。 本计画将从分子的小尺度运动来研究分子，并特别著重于酵素活性位的动力学。 由此产生的知识将有助于对生命过程的基本理解。 在这项研究中，将使用尽可能高的磁场强度的核磁共振技术。