A Computational Study of Iron Binding at the Human H Ferritin Ferroxidase Center

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The goal of the project is to define the structures and energetics of the complexes between iron and the ferroxidase center of ferritin. The principal method employed will be accurate all-electron density functional theoretical calculations. Ferritin is the primary cellular iron-storage protein, present in the cells of living organisms from bacteria to mammals. In the ferroxidase reaction Fe2+ is bound in pairs, oxidized by O2 to iron oxide and transported to the central cavity of the protein. Ferritin, therefore, lies at the intersection of the iron and oxygen regulatory systems. The ferroxidase reaction is intensely studied, but the structures of bound iron complexes remain undefined due to the rapidity of reaction. A minimal model of the active center will be developed, which will be based on the six amino acids found experimentally to be crucial to ferroxidase activity. In addition to all-electron density functional calculations, Monte Carlo and molecular dynamics statistical simulations will be employed to explore the potential energy surface of the model center and to define its hydration sphere. The effect of neighboring amino acids on the structure of the model center and the hydration sphere will also be examined. The research will be conducted at Universidad Metropolitana in San Juan, Puerto Rico and the participating students will be Hispanic. The project will broaden the scope of undergraduate research at the university to include molecular biology and it will also widen the research themes to be introduced into courses in biology and chemistry. Computational molecular biology capability is in demand in Puerto Rico. The project will increase the abilities of the researchers to address this need, and the computer hardware purchased will enhance the computational facilities devoted exclusively to this area. The results of the research will be disseminated broadly. Local high school teachers who attend the seminar on technology in secondary-school science at UMET will be apprised of the progress of the project.