Proton transport pathways in [NiFe]-hydrogenase.

Hydrogenases reversibly catalyze the production of molecular hydrogen. Current interest in these enzymes is focused on understanding the catalysis, since this may prove useful for hydrogen-based fuel cell and photosynthetic hydrogen production cell technologies. A key step in the hydrogenase catalytic cycle and the focus of this work is proton transport (PT) to and from the active site. The PT mechanism of the enzyme is studied using reactive molecular dynamics simulations of the full protein and the excess proton transfers via the multistate empirical valence bond (MS-EVB) method. Pathways connecting the bulk and the active site are located that suggest possible participation by several protonatable residues. PT free energy surfaces are calculated to differentiate the pathways.