Theoretical calculations of the electronic structure of iron-oxo dimer complexes relevant to biology are now making important contributions to bioinorganic chemistry. High-accuracy density functional theory (DFT) methods are used to describe the transition metal dimer complex active site. The active site complex is then embedded in the longer range protein and solvent environment using an electrostatics and dielectric based representation for the evaluation of energetic interactions. The long-term goal is to develop a detailed understanding of critical intermediates, enzymatic mechanisms, reaction pathways, and energetics in iron-oxo dimer enzymes. These features will be related to the underlying electronic and geometric structure of the active site as a function of oxidation state, ligand environment and the protein surroundings. The iron-oxo enzymes to be studied are methane monooxygenase (MMO) and ribonucleotide reductase (RNR), which hydroxylate alkanes and reduce ribonucleotides (NDP) to deoxyribonucleotides (dNDP), respectively. The major goals of the project include: (1) Using DFT methods to calculate optimal active site geometries with associated energies for a number of feasible structures of key intermediates in MMO and RNR, which will then be compared with experimental structural results from spectroscopies or X-ray structures; (2) To evaluate reaction pathways and comparative energetics of different enzymes and mutants; (3) To make important connections with experimental data by comparing calculated spectroscopic properties from DFT electronic structures with corresponding experimental results from optical, MCD, Mossbauer and ENDOR spectroscopies, and from magnetic susceptibility measurements. These comparisons are very important for those critical intermediates of the catalytic cycles where X-ray structures are not available, particularly intermediate Q of MMO and intermediate X of RNR; (4) To extend and improve the current quantum mechanics/electrostatics methodology to full quantum mechanics/molecular mechanics (QM/MM) with multiple dielectric regions for the quantum cluster, protein and solvent.
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