Structure and redox properties of the protein, rubredoxin, and its ligand and metal mutants studied by electronic structure calculation

The changes in the structural and electronic properties accompanying metal ionization of the iron-containing protein, rubredoxin, and of some ligand and metal mutants, have been explored using density functional theory (DFT) calculations of the metal atom coordinated to the four immediate residues. Both isolated and embedded cluster studies have been carried out, the latter using the hybrid quantum mechanics/molecular mechanics (QM/MM) approach. The replacement of a cysteine by a serine residue has a considerable effect on both the electronic and geometric structure of the core, which can be qualitatively understood on the basis of the isolated cluster studies. The modulation of these properties caused by the protein environment is quite accurately described by the QM/MM calculations. The predicted core geometries are in good accord with both X-ray and EXAFS data, and the changes in the redox potentials are predicted, at least semiquantitatively, by considering only the core part of the protein. © 2006 American Chemical Society.