Pathways of H 2 toward the Active Site of [NiFe]-Hydrogenase

Abstract

Hydrogenases catalyze the reversible oxidation of molecular hydrogen (H 2), but little is known about the diffusion of H 2 toward the active site. Here we analyze pathways for H 2 permeation using molecular dynamics (MD) simulations in explicit solvent. Various MD simulation replicates were done, to improve the sampling of the system states. H 2 easily permeates hydrogenase in every simulation and it moves preferentially in channels. All H 2 molecules that reach the active site made their approach from the side of the Ni ion. H 2 is able to reach distances of <4 Å from the active site, although after 6 Å permeation is difficult. In this region we mutated Val-67 into alanine and perform new MD simulations. These simulations show an increase of H 2 inside the protein and at lower distances from the active site. This valine can be a control point in the H 2 access to the active center.