Theoretical Studies On The Dynamic Aspects Of Macromolec

高分子动态方面的理论研究

• 批准号: 6542222
• 负责人: Attila Szabo
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6542222
• 关键词: atomic force microscopy; calmodulin; chemical association; chemical kinetics; chemical models; chemical structure function; computer simulation; conformation; diffusion; ligands; macromolecule; mathematical model; membrane channels; micromanipulator; molecular dynamics; nanotechnology; nuclear magnetic resonance spectroscopy; photochemistry; thermodynamics

In this reporting period, papers dealing with the following projects appeared in print: (1) Particle number fluctuations in a membrane channel; (2) Free energy reconstruction from non equilibrium single molecule pulling experiments; (3) Analysis of slow interdomain motion of macromolecules using NMR relaxation data; (4) Long time tails in the kinetics of reversible reactions; (5) Irreversible reactions of Langevin particles. The first three deal directly with the theory required to analyze experiments and the focus will be on these. The first deals with the problem of how to analyse the excess noise in the electric current through membranes to learn about the channel-facilated transport of metabolites. The second solves the important outstanding problem of how to obtain thermodynamic information from micromanipulation of single molecules using lazer tweezers and atomic force microscopes. In such experiments a molecule is forced to undergo conformational changes by pulling on it. Thus the system is driven away from equilibrium. We show how one can extract the energetics of equilibrium conformational changes from repeated force experiments. Thirdly, we show how NMR relaxation data should be interpreted to yield information about the nature of slow interdomain motions of macromolecules. This work focused on calmodulin(CaM) which consists of two domains connected by a flexible helical linker. We were able the determine both the timescale and amplitude of the relative motion of the two domains. This is functionally important because many signalling pathways involve the clamping of a target peptide between the two domains of CaM. It is expected that the method developped in this paper will be widely used.

在本报告所述期间，发表了关于下列项目的论文：（1）膜通道中的粒子数波动;（2）从非平衡单分子拉伸实验中重建自由能;（3）用NMR弛豫数据分析大分子的慢域间运动;（4）可逆反应动力学中的长时间拖尾;（5）用NMR弛豫数据分析大分子的慢域间运动。 (5)Langevin粒子的不可逆反应前三个直接涉及分析实验所需的理论，重点将放在这些。第一个涉及的问题是如何分析通过膜的电流中的过量噪声，以了解代谢物的通道促进运输。第二个解决了如何利用激光镊子和原子力显微镜对单分子进行显微操作以获得热力学信息这一重要而突出的问题。在这样的实验中，分子受到拉力而被迫发生构象变化，从而使系统偏离平衡。我们展示了如何从重复的力实验中提取平衡构象变化的能量。第三，我们展示了如何解释NMR弛豫数据，以产生有关大分子慢域间运动的性质的信息。本工作的重点是钙调素（CaM），它由两个结构域连接的一个灵活的螺旋接头。 我们能够确定两个域的相对运动的时间尺度和幅度。这在功能上是重要的，因为许多信号传导途径涉及在CaM的两个结构域之间夹持靶肽。该方法具有广泛的应用前景。