Fast generation of broken‐symmetry states in a large system including multiple iron–sulfur assemblies: Investigation of QM/MM energies, clusters charges, and spin populations

Abstract

A density functional theory study is presented regarding the energetics and the Mulliken population analyses of a quantum mechanical/molecular mechanical (QM/MM) system including multiple iron-sulfur clusters in the QM region. The [FeFe]-hydrogenase from Desulfovibrio desulfuricans was studied, and both the active site (an Fe 6 S 6 assembly generally referred to as the H-cluster) and an ancillary Fe 4 S 4 site were treated at the BP86-RI/TZVP level. The antiferromagnetic coupling that characterizes both sites was modeled using the broken-symmetry (BS) approach. For such a QM system, 36 different BS couplings can be defined, depending on the localization of spin excess on the various spin centers. All the BS states were obtained by means of an effective and simple method for spin localization, that is here described and compared with more sophisticated approaches already available in literature. The variation of the QM/MM energy among the various geometry-optimized protein models was found to be less than 25 kJ mol -1 . This energy variation almost doubles if no geometry optimization is performed. A detailed analysis of the additive nature of these variations in QM/MM energy is reported. The Mulliken charges show very small variations among the 36 BS states, whereas the Mulliken spin populations were found to be somewhat more variable. The relevance of such variations is discussed in light of the available Mö ssbauer and Electron Paramagnetic Resonance (EPR) spectroscopic data for the enzyme. Finally, the influence of the basis set on the spin populations, charges, and structural parameters of the models was investigated, by means of QM/MM computations on the same system at the BP86-RI/SVP level.

Mechanistic and Physiological Implications of the Interplay among Iron–Sulfur Clusters in [FeFe]-Hydrogenases. A QM/MM Perspective

“…35 The use of the SVP basis has been previously validated. 27 B3LYP gives unpaired spins distributions that are in better agreement with EPR and Mössbauer experimental data when compared with results obtained using pure functionals. 36 However, calculations were carried out also at the BP86/SVP level, and the conclusions one can draw from the latter results are compatible with the picture coming from B3LYP/SVP optimizations (see Supporting Information).…”

Isocyanide in Biochemistry? A Theoretical Investigation of the Electronic Effects and Energetics of Cyanide Ligand Protonation in [FeFe]‐Hydrogenases

“…In order to obtain such a BS coupling scheme in the various models, we used an approach that we developed recently. [17] QM/MM modeling: In the QM/MM calculations, the protein was divided into three subsystems. System 1 was treated at QM level, and was allowed to relax.…”

Probing the Effects of One‐Electron Reduction and Protonation on the Electronic Properties of the Fe‐S Clusters in the Active‐Ready Form of [FeFe]‐Hydrogenases. A QM/MM Investigation.

“…However, in a previous study on [FeFe]-hydrogenases we have shown that the overall Mulliken charges of the Fe 4 S 4 clusters are essentially unaffected by the particular BS wavefunction chosen. [33] All the results reported in the Result and Discussion section are based on the BS coupling scheme shown in Figure 6. The spin excess pattern in the [4 Fe4 S] H subcluster and in the F-and F'-clusters were directly obtained from standard SCF calculations, as described previously.…”

“…The use of the SVP basis has been validated previously. [33] In the QM calculations, all atoms in system 2 were represented by partial point charges. These charges were included in the Hamiltonian of the QM calculations, and thus the quantum chemical system was polarized by the atoms of system 2 in a self-consistent way.…”