Ab Initio Quantum Mechanical Study of Metal Substitution in Analogues of Rubredoxin:  Implications for Redox Potential Control

Abstract

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 that metal substitution changes only intrinsic properties of the redox site such as the ionization potential without altering the surrounding protein or solvent. However, if this is not true, structural studies of metal-substituted proteins will not reflect the native protein and the differences in redox potential upon metal substitution will not be simply the differences in ionization potential of the redox sites because of perturbations in the extrinsic electric field. Here, we present an ab initio unrestricted Hartree−Fock 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. Variations in several physical properties were determined and compared to experimental data. Upon metal substitution, only minor variations in geometry, atomic 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 made into an Fe−S metalloprotein, little change will occur in the interactions between the metal site and the surrounding protein and thus the surrounding protein structure and the resultant electric field will not change. Thus, the structure is relevant to the native protein and the redox properties are mainly determined by the variations in the intrinsic ionization potential of the metal site and not the extrinsic field of the surrounding protein and solvent.

Quantitative Account of the Bonding Properties of a Rubredoxin Model Complex [Fe(SCH3)4]q, q = −2, −1, +2, +3

“…The inherited correlated character of transition metals, further complicated by the presence of low-lying excited states with a complex electronic structure due to the large number of nearly degenerate states, necessitates the use of electronic structure methods that can capture the details of the multireference character of these complexes. Therefore, we extend previous studies performed at the DFT and MP2 levels of theory ,,− by applying both coupled cluster and multiconfiguration electronic structure theories for the ground and low-lying excited states. As a preliminary stage toward the study of multicenter Fe/S clusters, we demonstrate that these methods yield very accurate reduction and dissociation energies and offer detailed physical insights into their electronic structure that regulates the nature and strengths of the Fe–S bonds and their overall redox properties.…”

“…They exhibit a considerably more negative range of redox potentials than the natural clusters, in most cases −0.1 to −1.1 V versus SHE, and generally, the Fe center adopts a tetrahedral high-spin geometry . Many theoretical studies on simple Fe–S complexes with one Fe active site, such as [Fe­(SH) 4 ] 1–/2– and [Fe­(SCH 3 ) 4 ] 1–/2– , have been carried out mainly at the Hartree–Fock (HF) and DFT level of theory, ,− and via coupled cluster and second-order Møller–Plesset (MP2) methods. The [Fe­(SCH 3 ) 4 ] 1–/2– complexes have been studied experimentally via photoelectron , and photodetachment spectroscopies.…”

Theoretical Study of DNA Damage Recognition via Electron Transfer from the [4Fe-4S] Complex of MutY

“…To incorporate the contribution of the outer shell, we obtain the atomic charges of the quantum part by fitting to the electrostatic potential (38) calculated from the QM calculation. The calculated atomic charges are then used as parts of the force field, with other parameters which were used in studies of similar structures (39)(40)(41), for the residues of the inner shell for the subsequent classical treatment of the whole protein-DNA complex. With the fixed optimized structure of the [4Fe-4S] cluster from SIESTA, we carried out the free energy calculation for the MutY-DNA complex using the MD package AMBER 8 with the PARM99 force field (42,43) and with a TIP3P water model (44).…”

Calculation of the Redox Potential of the Protein Azurin and Some Mutants

“…Since extensive sampling of atomic motion in combination with high-level electronic-structure calculations is not practicable for systems of the required size and complexity, one must make one or more simplifying assumptions: i) One may treat the copper ion and its ligands using highlevel quantum-chemical methodology, but neglect the protein environment, the solution and entropic contributions. [11][12][13] ii) One may treat the protein in explicit solvent using an empirical force field and classical dynamics. This approach includes entropic effects through extensive conformational sampling.…”