Ab initio quantum mechanical study of metal substitution in analogues of rubredoxin: Implications for redox potential control

Substitution of different metals into the redox sites of metalloproteins is a means of studying the structure of the native protein and of varying the redox properties of the protein. The implicit assumption is often made tha t metal substitution changes only intrinsic properties of the redox site su ch as the ionization potential without altering the surrounding protein or solvent. However, if this is not true, structural studies of metal-substitu ted proteins will not reflect the native protein and the differences in red ox potential upon metal substitution will not be simply the differences in ionization potential of the redox sites because of perturbations in the ext rinsic electric field. Here, we present an ab initio unrestricted Hartree-F ock quantum mechanical study of metal substitution in the [M(SCH3)(4))(2-/1 -) analogue, where M = Fe, Co, Ni, and Zn, of the protein rubredoxin. Varia tions in several physical properties were determined and compared to experi mental data. Upon metal substitution, only minor variations in geometry, at omic spin, and atom-centered partial charges of the redox site are observed . However, significant variation is found in the energies of reduction, on the order of 100-1000 mV. This indicates that when such substitutions are m ade into an Fe-S metalloprotein, little change will occur in the interactio ns between the metal site and the surrounding protein and thus the surround ing protein structure and the resultant electric field will not change. Thu s, the structure is relevant to the native protein and the redox properties are mainly determined by the variations in the intrinsic ionization potent ial of the metal site and not the extrinsic field of the surrounding protei n and solvent.