A wide variety of iron-sulfur clusters and related mixed-metal species are found as active sites in metalloenzymes. In some cases these proteins form part of electron transport chains, and in other cases they serve as catalytic centers for quite unusual chemistry. Our research focuses on the use of modern techniques of quantum chemistry to carry out theoretical studies (at the spin Hamiltonian and density functional level) of their electronic structures, in an attempt to more closely connect the spectroscopy and energetics of these systems to their structure and function. Three (3) areas will be emphasized during the next period of this project. The first will be the nitrogenase system, catalyzing the reduction of dinitrogen to ammonia. Detailed quantum mechanical models will be prepared for the """"""""P"""""""" and """"""""M"""""""" clusters in the molybdenum-iron protein. A second area will involve similar studies on carbon monoxide dehydrogenase/acetyl coenzyme A synthase (CODH/ACS), which catalyzes the oxidation of carbon monoxide and the synthesis of coenzyme A. A third task will involve the development and testing of molecular mechanics potentials to facilitate molecular dynamics simulations on iron-sulfur proteins. Overall, this work aims to create a theoretical and conceptual framework that supports integration of many types of spectroscopic and energetic data in a way that is helpful in understanding biochemical function. A key technical advance will involve the development of molecular mechanics potentials (using a novel means of describing distortions of iron-sulfur clusters); this will allow the effects of fluctuations in the protein and solvent environment to be connected to quantum simulations of the metal-centered active sites in a more natural way.
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