Molecular Computational Investigation of Electron-Transfer Kinetics Across Cytochrome−Iron Oxide Interfaces

The interface between electron-transfer proteins such as cytochromes and solid-phase mineral oxides is central to the activity of dissimilatory-metal reducing bacteria. A combination of potential-based molecular dynamics simulations and ab initio electronic structure calculations are used in the framework of Marcus's electron-transfer theory to compute elementary electron-transfer rates from a well-defined cytochrome model, namely, the small tetraheme cytochrome (STC) from Shewanella oneidensis, to surfaces of the iron oxide mineral hematite (α-Fe 2 O 3 ). Room-temperature molecular dynamics simulations show that an isolated STC molecule favors surface attachment via direct contact of hemes I and IV at the poles of the elongated axis, with electron-transfer distances as small as 9 Å. The cytochrome remains attached to the mineral surface in the presence of water and shows limited surface diffusion at the interface. Ab initio electronic coupling matrix element ( V AB ) calculations of configurations excised from the molecular dynamics simulations reveal V AB values ranging from 1 to 20 cm -1, consistent with nonadiabaticity. Using these results, together with experimental data on the redox potential of hematite and hemes in relevant cytochromes and calculations of the reorganization energy from cluster models, we estimate the rate of electron transfer across this model interface to range from 1 to 1000 s -1 for the most exothermic driving force considered in this work and from 0.01 to 20 s -1 for the most endothermic. This fairly large range of electron-transfer rates highlights the sensitivity of the rate upon the electronic coupling matrix element, which is in turn dependent on the fluctuations of the heme configuration at the interface. We characterize this dependence using an idealized bisimidazole heme to compute from first principles the V AB variation due to porphyrin ring orientation, electron-transfer distance, and mineral surface termination. The electronic matrix element and consequently the rate of electron transfer are found to be sensitive to all parameters considered. This work indicates that biomolecularly similar solvent-exposed bishistidine hemes in outer-membrane cytochromes such as MtrC or OmcA are likely to have an affinity for the oxide surface in water governing the approach and interfacial conformation and, if allowed sufficient conformational freedom, will achieve distances and configurations required for direct interfacial electron transfer.