Investigation of the Membrane Anchor of Human N-Ras by Experimental Approaches, Analytical Models and Molecular Dynamics Simulations

通过实验方法、分析模型和分子动力学模拟研究人类 N-Ras 的膜锚

• 批准号: 44110649
• 负责人: Dr. Alexander Vogel
• 金额: --
• 依托单位: Institut für Medizinische Physik und Biophysik
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/44110649?language=en
• 关键词: Investigation; Membrane; Anchor; Human; Ras

Ras proteins are membrane bound proteins that play a crucial role in signal transduction and are involved in cancer development. While many molecular details of the membrane anchoring domain of Ras proteins are still unknown the manipulation of the membrane association proposes a possible way of treating cancer diseases. Therefore, the aim of the planned project is the development of a detailed model of the membrane anchoring domain of human N-Ras. The lipid modifications that mediate the membrane association of N-Ras and many other proteins are of particular interest in the investigations. Their dynamics will be analyzed by application of solid-state NMR spectroscopy, complex analytical models, and very long MD-simulations. Further, the propensity of N-Ras for membrane rafts will be investigated using a new experimental approach which represents an advancement of an approach formerly developed by the applicant. The combination of these methods and experimental approaches will enable the determination of the dynamics and function of the membrane binding domain of human N-Ras with detail and precision that has never been reached before for a component of a biological membrane.

Ras蛋白是膜结合蛋白，在信号转导中起关键作用，并参与癌症的发展。虽然Ras蛋白的膜锚定结构域的许多分子细节仍然是未知的，但操纵膜缔合提出了治疗癌症疾病的可能方法。因此，计划项目的目标是开发人类N-Ras膜锚定域的详细模型。介导N-Ras和许多其他蛋白质的膜缔合的脂质修饰在调查中特别感兴趣。它们的动力学将通过应用固态NMR光谱，复杂的分析模型和非常长的MD模拟来分析。此外，N-Ras用于膜筏的倾向将使用新的实验方法进行研究，该方法代表了申请人先前开发的方法的进步。这些方法和实验方法的组合将使得能够确定的动态和功能的膜结合域的人N-Ras的细节和精度，以前从未达到的生物膜的组件。