I plan to simulate the electrostatic interaction between the superoxide dismutase dependant on Cu/Zn (CuZnSOD) and some mutants of it that have been implicated in the familial amiotrophic lateral sclerosis (FALS) with hydrogen peroxide. In order to perform these molecular simulations, I will use well stablished computational tools developed by Prof. James A. McCammon, with whom I will collaborate for these studies. The goal of these calculations is to determine the possible amino acid residues responsible for direct interaction with hydrogen peroxide in CuZnSOD wild-type form and some mutants. To test our calculations, I plan to construct mutants in the positions selected from the electrostatic simulations, and biochemically characterize them. The relevance of this study relies on the possibility to stablish the molecular basis to differentiate FALS from ALS, and to treat specifically FALS.
