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

RAS蛋白是一种膜结合蛋白，在信号转导中起关键作用，参与肿瘤的发生发展。虽然RAS蛋白的膜锚定结构域的许多分子细节仍不清楚，但对膜结合的操纵提出了一种治疗癌症疾病的可能方法。因此，计划中的项目的目标是开发一个详细的人N-RAS膜锚定结构域模型。调节N-RAS和许多其他蛋白质的膜结合的脂质修饰在研究中特别感兴趣。他们的动力学将通过应用固态核磁共振波谱、复杂的分析模型和非常长的MD-模拟来分析。此外，将使用一种新的实验方法来研究膜筏中N-RAS的倾向，这代表了申请人以前开发的方法的进步。这些方法和实验方法的结合将使人N-RAS膜结合域的动力学和功能的测定变得更加详细和精确，这是以前对生物膜组分所从未达到的。

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.