Polaronic structure of excess electrons and holes for a series of bulk iron oxides.

Iron oxides such as hematite (α-Fe2O3) play an important role in diverse fields ranging from biogeochemistry to photocatalysis. Here we perform calculations of both the electron and electron hole polaron structures and associated reorganisation energies for a series of bulk iron oxides: hematite (α-Fe2O3), lepidocrocite (γ-FeOOH), goethite (α-FeOOH) and white rust (Fe(OH)2). Through the use of gap-optimized hybrid functionals and large supercells under periodic boundary conditions, we remove some of the complications and uncertainties present in earlier cluster model calculations. It is found that while the electron hole polaron in these materials generally localises onto a single iron site, the electron polaron localises across two iron sites of the same spin layer as a consequence of the lower reorganisation energy for electrons compared to holes. An exception to these trends is the hole of goethite, which according to our calculations does not form a localised polaron.

Kinetics of trifurcated electron flow in the decaheme bacterial proteins MtrC and MtrF.

The bacterium Shewanella oneidensis has evolved a sophisticated electron transfer (ET) machinery to export electrons from the cytosol to extracellular space during extracellular respiration. At the heart of this process are decaheme proteins of the Mtr pathway, MtrC and MtrF, located at the external face of the outer bacterial membrane. Crystal structures have revealed that these proteins bind 10 c-type hemes arranged in the peculiar shape of a staggered cross that trifurcates the electron flow, presumably to reduce extracellular substrates while directing electrons to neighboring multiheme cytochromes at either side along the membrane. Especially intriguing is the design of the heme junctions trifurcating the electron flow: they are made of coplanar and T-shaped heme pair motifs with relatively large and seemingly unfavorable tunneling distances. Here, we use electronic structure calculations and molecular simulations to show that the side chains of the heme rings, in particular the cysteine linkages inserting in the space between coplanar and T-shaped heme pairs, strongly enhance electronic coupling in these two motifs. This results in an [Formula: see text]-fold speedup of ET steps at heme junctions that would otherwise be rate limiting. The predicted maximum electron flux through the solvated proteins is remarkably similar for all possible flow directions, suggesting that MtrC and MtrF shuttle electrons with similar efficiency and reversibly in directions parallel and orthogonal to the outer membrane. No major differences in the ET properties of MtrC and MtrF are found, implying that the different expression levels of the two proteins during extracellular respiration are not related to redox function.

Cysteine Linkages Accelerate Electron Flow through Tetra-Heme Protein STC.

Multi-heme proteins have attracted much attention recently due to their prominent role in mediating extracellular electron transport (ET), but one of their key fundamental properties, the rate constants for ET between the constituent heme groups, have so far evaded experimental determination. Here we report the set of heme-heme theoretical ET rate constants that define electron flow in the tetra-heme protein STC by combining a novel projector-operator diabatization approach for electronic coupling calculation with molecular dynamics simulation of ET free energies. On the basis of our calculations, we find that the protein limited electron flux through STC in the thermodynamic downhill direction (heme 1→4) is ∼3 × 106 s-1. We find that cysteine linkages inserting in the space between the two terminal heme pairs 1-2 and 3-4 significantly enhance the overall electron flow, by a factor of about 37, due to weak mixing of the sulfur 3p orbital with the Fe-heme d orbitals. While the packing density model, and to a higher degree, the pathway model of biological ET partly capture the predicted rate enhancements, our study highlights the importance of the atomistic and chemical nature of the tunneling medium at short biological tunneling distances. Cysteine linkages are likely to enhance electron flow also in the larger deca-heme proteins MtrC and MtrF, where heme-heme motifs with sub-optimal edge-to-edge distances are used to shuttle electrons in multiple directions.

Mechanism of O2 diffusion and reduction in FeFe hydrogenases.

FeFe hydrogenases are the most efficient H2-producing enzymes. However, inactivation by O2 remains an obstacle that prevents them being used in many biotechnological devices. Here, we combine electrochemistry, site-directed mutagenesis, molecular dynamics and quantum chemical calculations to uncover the molecular mechanism of O2 diffusion within the enzyme and its reactions at the active site. We propose that the partial reversibility of the reaction with O2 results from the four-electron reduction of O2 to water. The third electron/proton transfer step is the bottleneck for water production, competing with formation of a highly reactive OH radical and hydroxylated cysteine. The rapid delivery of electrons and protons to the active site is therefore crucial to prevent the accumulation of these aggressive species during prolonged O2 exposure. These findings should provide important clues for the design of hydrogenase mutants with increased resistance to oxidative damage.

Multi-haem cytochromes in Shewanella oneidensis MR-1: structures, functions and opportunities.

Multi-haem cytochromes are employed by a range of microorganisms to transport electrons over distances of up to tens of nanometres. Perhaps the most spectacular utilization of these proteins is in the reduction of extracellular solid substrates, including electrodes and insoluble mineral oxides of Fe(III) and Mn(III/IV), by species of Shewanella and Geobacter. However, multi-haem cytochromes are found in numerous and phylogenetically diverse prokaryotes where they participate in electron transfer and redox catalysis that contributes to biogeochemical cycling of N, S and Fe on the global scale. These properties of multi-haem cytochromes have attracted much interest and contributed to advances in bioenergy applications and bioremediation of contaminated soils. Looking forward, there are opportunities to engage multi-haem cytochromes for biological photovoltaic cells, microbial electrosynthesis and developing bespoke molecular devices. As a consequence, it is timely to review our present understanding of these proteins and we do this here with a focus on the multitude of functionally diverse multi-haem cytochromes in Shewanella oneidensis MR-1. We draw on findings from experimental and computational approaches which ideally complement each other in the study of these systems: computational methods can interpret experimentally determined properties in terms of molecular structure to cast light on the relation between structure and function. We show how this synergy has contributed to our understanding of multi-haem cytochromes and can be expected to continue to do so for greater insight into natural processes and their informed exploitation in biotechnologies.

A microscopic model for gas diffusion dynamics in a [NiFe]-hydrogenase.

We describe and apply a microscopic model for the calculation of gas diffusion rates in a [NiFe]-hydrogenase. This enzyme has attracted much interest for use as a H(2) oxidising catalyst in biofuel cells, but a major problem is their inhibition by CO and O(2). In our model, the diffusive hopping of gas molecules in the protein interior is coarse grained using a master equation approach with transition rates estimated from equilibrium and non-equilibrium pulling simulations. Propagating the rate matrix in time, we find that the probability for a gas molecule to reach the enzyme active site follows a mono-exponential increase. Fits to a phenomenological rate law give an effective diffusion rate constant for CO that is in very good agreement with experimental measurements. We find that CO prefers to move along the canonical 'hydrophobic' main channel towards the active site, in contrast to O(2) and H(2), which were previously shown to explore larger fractions of the protein. Differences in the diffusion of the three gases are discussed in light of recent efforts to engineer a gas selectivity filter in the enzyme.

Absolute pKa Values and Solvation Structure of Amino Acids from Density Functional Based Molecular Dynamics Simulation.

Absolute pKa values of the amino acid side chains of arginine, aspartate, cysteine, histidine, and tyrosine; the C- and N-terminal group of tyrosine; and the tryptophan radical cation are calculated using a revised density functional based molecular dynamics simulation technique introduced previously [ Cheng , J. ; Sulpizi , M. ; Sprik , M. J. Chem. Phys. 2009 , 131 , 154504 ]. In the revised scheme, acid deprotonation is considered as a dissociation rather than a proton transfer reaction, and a correction term for treating the proton as a hydronium ion is suggested. The acidity constants of the amino acids are obtained from the vertical energy gaps for removal or insertion of the acidic proton and the computed solvation free energy of the proton. The unsigned mean error relative to experimental results is 2.1 pKa units with a maximum error of 4.0 pKa units. The estimated mean statistical uncertainty due to the finite length of the trajectories is ±1.1 pKa units. The solvation structures of the protonated and deprotonated amino acids are analyzed in terms of radial distribution functions, which can serve as reference data for future force field developments.