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

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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.