Glycophorin A (GpA)

Christophe Chipot and Andrew Pohorille

We propose to study the molecular mechanism of recognition and association of protein helical segments in membranes. These processes are crucial for proper functioning of a cell. As a model system we choose a membrane spanning domain of glycophorin A embedded in a membrane-mimicking material. Glycophorin A is a well studied protein which forms dimers of -helices in lipid bilayers (see Figure). Using large-scale molecular dynamics simulations and free energy calculation methods we will determine the free energy of association of these helices for the wild type and mutants that disrupt dimerization. We will further examine the mechanism and energetics of insertion of the protein into the membrane. The results should yield new insights into structural and energetic factors that influence recognition and association of helices in membranes and should be useful in designing functional membrane proteins for biotechnological purposes. The proposed work will be performed as an international collaboration with scientists at CNRS in Nancy, France. Combining computational resources and complementary skills will be the main benefits from carrying out the research in a collaborative fashion.