Structure,strain, and reorganization energy of blue copper models in the protein

The copper coordination geometry in the blue copper proteins plastocyanin, nitrite reductase, cucumber basic protein, and azurin has been studied by combined density functional (B3LYP) and molecular mechanical methods. Compared to quantum chemical vacuum calculations, a significant improvement of the geometry is seen (toward the experimental structures) not only for the dihedral angles of the ligands but also for the bond lengths and angles around the copper ion. The flexible Cu–S_Met bond is well reproduced in the oxidized structures, whereas it is too long in some of the reduced complexes (too short in vacuum). The change in the geometry compared to the vacuum state costs 33–66 kJ/mol. If the covalent bonds between the ligands and the protein are broken, this energy decreases by ∼25 kJ/mol, which is an estimate of the covalent strain. This is similar to what is found for other proteins, so the blue copper proteins are not more strained than other metalloproteins. The inner‐sphere self‐exchange reorganization energy of all four proteins are ∼30 kJ/mol. This is 30–50 kJ/mol lower than in vacuum. The decrease is caused by dielectric and electrostatic effects in the protein, especially the hydrogen bond(s) to the cysteine copper ligands and not by covalent strain. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 81: 335–347, 2001