Computational study of electron transport in [FeFe] hydrogenase enzymes

[FeFe] hydrogenase enzymes can reversibly catalyze the conversion of protons into molecular hydrogen. The active site of the [FeFe] hydrogenase enzyme is buried inside the protein. The transport of electrons and protons to the active site of the protein is crucial for an efficient catalytic cycle. A chain of iron-sulfur cubane cofactors forms a pathway for the electron transfer in these [FeFe] hydrogenases. We have studied the electron transfer process via the iron-sulfur clusters in the enzyme using classical molecular dynamics simulations. Our simulations show that the protein matrix acts as a porous medium for the transport of water molecules in and out during the electron transfer process. When an electron is transferred through the pathway, solvent water molecules penetrate the protein, forming hydrogen bonded networks and hydrating the electron accepting cubane clusters. The reorganization of the protein and the penetrating water molecules have a large effect on the free energy landscape of the electron transfer, via the formation of favorable hydrogen bonds with the reduced iron- sulfur cluster, thereby stabilizing the electron at the cofactors.