Determination of Force Field Parameters for the Octahedral Iron Complex in Lipoxygenase 1 Determination of Force Field Parameters for the Octahedral Iron Complex in Lipoxygenase

Lipoxygenases catalyze the positionand stereospecific dioxygenation of fatty acids and lipids to chiral conjugated hydroperoxy fatty acids. They are found in all higher organisms. Their products are the precursors of a number of physiological effectors. Some details of the catalytic mechanisms of these enzymes are still not known. In particular, it is unclear how molecular oxygen penetrates deep into the binding pocket and how the fatty acid substrate is aligned to the active site containing an octahedral iron complex. To address these important points we plan to perform extensive molecular dynamics (MD) simulations. A necessary prerequisite for these calculations is to determine the force field parameters used in MD describing the molecular interactions regarding the iron complex in a physically reliable manner. In this complex, the iron is coordinated with four histidines, the C-terminal carboxy group and one hydroxy anion pointing into the binding pocket. During the reaction Fe3+ is reduced to Fe2+, consuming one electron which resulted from the abstraction of a hydrogen atom from the lipid substrate. The corresponding proton is taken up by the hydroxide.