Electronic structure calculations for the iron complexes at the active sites of iron-oxo and iron-peroxo based enzymes are now making an important contribution to understanding the physical properties and reaction chemistry of these systems. We use high-quality quantum mechanical density functional theory (DFT) methods to describe and analyze active site properties, and link this to an electrostatics-based representation of the longer range protein and solvent environment. Our long term goal to develop a detailed understanding of chemical bonding, reaction energetics and pathways, making a close connection with experimental structural, spectroscopic, and kinetics studies. (1) These DFT methods will be used to calculate accurate geometries, energies, and protonation states for critical intermediates of iron-oxo and iron-peroxo enzymes. The specific enzymes of interest are Class I ribonucleotide reductases (RNRs) methane monooxygenases (MMOs), toluene monoxygenases (Tolos) and Rieske oxygenases. (2) Detailed connections will be made to a number of X-ray, optical and electron/nuclear based spectroscopies. (3) Reaction pathways for these enzymes will be evaluated and compared with experimental kinetics. (4) New theoretical/computational methods will be tested and compared with experiment to further develop the power and analysis capabilities of modem chemical theory. RNRs catalyze the transformation of ribonucleotides to deoxyribonucleotides, the first required and often rate limiting step in DNA synthesis. Consequently, RNR is a drug target in anticancer, antiviral, and antibacterial therapies. MMOs, Tolos, and Rieske oxygenases have great potential for the detoxification of organic pollutants, and are promising as guides to finding environmentally nontoxic methods for the synthesis of valuable chemicals. A better understanding of these enzyme mechanisms should aid experimental work toward these goals.
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