Substrate Binding and Kinetic Aspects of the Peroxidation Reaction of Four Polyunsaturated Fatty Acids in the COX Active Site of PGHS-1

We examine trends in binding strength and activation barriers of four polyunsaturated fatty acids in the cyclooxygenase active site of PGHS-1 that influence the relative rates of oxygenation. A Natural Bond Orbital analysis at the B3LYP/6-31G level of theory is used to determine that the overall binding strength. Relative barriers for the rate-determining step are calculated at the B3LYP/3-21G level of theory.