PATHWAYS OF H2 TOWARDS THE ACTIVE SITE OF [NiFe]-HYDROGENASE

¹ Univ. Nova de Lisboa
² Universidade Nova de Lisboa

^* To whom correspondence should be addressed. E-mail: claudio{at}itqb.unl.pt.

Submitted on March 4, 2006
Revised on April 5, 2006
Accepted on 8 May 2006

	Abstract

Hydrogenases catalyse the reversible oxidation of molecular hydrogen (H₂), but little is known about the diffusion of H₂ towards the active site. Here we analyse pathways for H₂ permeation using molecular dynamics (MD) simulations in explicit solvent. Various MD simulation replicates were done, to improve the sampling of the system states. H₂ easily permeates hydrogenase in every simulation and it moves preferentially in channels. All H₂ molecules that reach the active site made their approach from the side of the Ni ion. H₂ is able to reach distances of less than 4 Å from the active site, although after 6 Å permeation is difficult. In this region we mutated Val67 into alanine and perform new MD simulations. These simulations show an increase of H₂ inside the protein, and at lower distances from the active site. This valine can be a control point in the H₂ access to the active centre.

Key Words: D. gigas [NiFe]-Hydrogenase, molecular dynamics simulations, molecular hydrogen pathways, mutations, protein channels

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