Density Functional Theory Calculation of Bonding and Charge Parameters for Molecular Dynamics Studies on [FeFe]...

We have developed and tested molecular mechanics parameters for [FeS] clusters found in known [FeFe] hydrogenases. Bond stretching, angle bending, dihedral and improper torsion parameters for models of the oxidized and reduced catalytic H-cluster, [4Fe4S](+,2+)Cys4, [4Fe4S](+,2+)Cys3His, and [2Fe2S](+,2+)Cys4, were calculated solely from Kohn-Sham density functional theory and Natural Population Analysis. Circumsphere analysis of the cubane clusters in the energy-minimized structure of the full Clostridium pasteurianum hydrogenase I showed the resulting metallocluster structures to be similar to known cubane structures. All clusters were additionally stable in molecular dynamics simulations over the course of 1.0 ns in the fully oxidized and fully reduced enzyme models. Normal modes calculated by quasiharmonic analysis from the dynamics data show unexpected couplings among internal coordinate motions, which may reflect the effects of the protein structure on metallocluster dynamics.