A microscopic model for gas diffusion dynamics in a [NiFe]-hydrogenase.

We describe and apply a microscopic model for the calculation of gas diffusion rates in a [NiFe]-hydrogenase. This enzyme has attracted much interest for use as a H2 oxidising catalyst in biofuel cells, but a major problem is their inhibition by CO and O2. In our model, the diffusive hopping of gas molecules in the protein interior is coarse grained using a master equation approach with transition rates estimated from equilibrium and non-equilibrium pulling simulations. Propagating the rate matrix in time, we find that the probability for a gas molecule to reach the enzyme active site follows a mono-exponential increase. Fits to a phenomenological rate law give an effective diffusion rate constant for CO that is in very good agreement with experimental measurements. We find that CO prefers to move along the canonical ‘hydrophobic’ main channel towards the active site, in contrast to O2 and H2, which were previously shown to explore larger fractions of the protein. Differences in the diffusion of the three gases are discussed in light of recent efforts to engineer a gas selectivity filter in the enzyme.