Structural, Solvent, and Temperature Effects on Protein Junction Conductance.

Cytochrome is a small redox-active heme protein that has served as an important model system for understanding biological electron transfer processes. Here, we present a comprehensive theoretical study of electron transport mechanisms in protein-metal junctions incorporating cytochrome using a multi-scale computational approach. Employing molecular dynamics (MD) simulations, we generated junction geometries for both vacuum-dried and solvated conditions, with the protein covalently bound to gold contacts in various configurations.

Shallow conductance decay along the array of a single tetraheme protein wire.

Multiheme cytochromes (MHCs) are the building blocks of highly conductive micrometre-long supramolecular wires found in so-called electrical bacteria. Recent studies have revealed that these proteins possess a long supramolecular array of closely packed cofactors along the main molecular axis alternating between perpendicular and stacking configurations (TST = T-shaped, stacked, T-shaped). While TST arrays have been identified as the likely electron conduit, the mechanisms of outstanding long-range charge transport observed in these structures remain unknown.

Electrochemistry in sensing of molecular interactions of proteins and their behavior in an electric field.

Electrochemical methods can be used not only for the sensitive analysis of proteins but also for deeper research into their structure, transport functions (transfer of electrons and protons), and sensing their interactions with soft and solid surfaces. Last but not least, electrochemical tools are useful for investigating the effect of an electric field on protein structure, the direct application of electrochemical methods for controlling protein function, or the micromanipulation of supramolecular protein structures. There are many experimental arrangements (modalities), from the classic configuration that works with an electrochemical cell to miniaturized electrochemical sensors and microchip platforms.

Applicability of perturbed matrix method for charge transfer studies at bio/metallic interfaces: a case of azurin.

As the field of nanoelectronics based on biomolecules such as peptides and proteins rapidly grows, there is a need for robust computational methods able to reliably predict charge transfer properties at bio/metallic interfaces. Traditionally, hybrid quantum-mechanical/molecular-mechanical techniques are employed for systems where the electron hopping transfer mechanism is applicable to determine physical parameters controlling the thermodynamics and kinetics of charge transfer processes. However, these approaches are limited by a relatively high computational cost when extensive sampling of a configurational space is required, like in the case of soft biomatter.

Tunneling-to-Hopping Transition in Multiheme Cytochrome Bioelectronic Junctions.

Multiheme cytochromes (MHCs) have attracted much interest for use in nanobioelectronic junctions due to their high electronic conductances. Recent measurements on dry MHC junctions suggested that a coherent tunneling mechanism is operative over surprisingly long long distances (>3 nm), which challenges our understanding of coherent transport phenomena. Here we show that this is due to (i) a low exponential distance decay constant for coherent conduction in MHCs (β = 0.

Adsorption of Hexavalent Chromium Using Activated Carbon Produced from ssp.: Comparison between Lab Experiments and Molecular Dynamics Simulations.

Adsorption is one of the most successful physicochemical approaches for removing heavy metal contaminants from polluted water. The use of residual biomass for the production of adsorbents has attracted a lot of attention due to its cheap price and environmentally friendly approach. The transformation of Sargassum-an invasive brown macroalga-into activated carbon (AC) via phosphoric acid thermochemical activation was explored in an effort to increase the value of Sargassum seaweed biomass.

Reorganization free energy of copper proteins in solution, in vacuum, and on metal surfaces.

Metalloproteins, known to efficiently transfer electronic charge in biological systems, recently found their utilization in nanobiotechnological devices where the protein is placed into direct contact with metal surfaces. The feasibility of oxidation/reduction of the protein redox sites is affected by the reorganization free energies, one of the key parameters determining the transfer rates. While their values have been measured and computed for proteins in their native environments, i.

Effects of Externally Applied Electric Fields on the Manipulation of Solvated-Chignolin Folding: Static- versus Alternating-Field Dichotomy at Play.

The interaction between a protein and external electric field (EF) can alter its structure and dynamical behavior, which has a potential impact on the biological function of proteins and cause uncertain health consequences. Conversely, the application of EFs of judiciously selected intensity and frequency can help to treat disease, and optimization of this requires a greater understanding of EF-induced effects underpinning basic protein biophysics. In the present study, chignolin─an artificial protein sufficiently small to undergo fast-folding events and transitions─was selected as an ideal prototype to investigate how, and to what extent, externally applied electric fields may manipulate or influence protein-folding phenomena.

HAB79: A new molecular dataset for benchmarking DFT and DFTB electronic couplings against high-level ab initio calculations.

A new molecular dataset called HAB79 is introduced to provide ab initio reference values for electronic couplings (transfer integrals) and to benchmark density functional theory (DFT) and density functional tight-binding (DFTB) calculations. The HAB79 dataset is composed of 79 planar heterocyclic polyaromatic hydrocarbon molecules frequently encountered in organic (opto)electronics, arranged to 921 structurally diverse dimer configurations. We show that CASSCF/NEVPT2 with a minimal active space provides a robust reference method that can be applied to the relatively large molecules of the dataset.

Dielectric properties of ice VII under the influence of time-alternating external electric fields.

The high-pressure solid phase of water known as ice VII has recently attracted a lot of attention when its presence was detected in large exoplanets, their icy satellites, and even in Earth's mantle. Moreover, a transition of ice VII to the superionic phase can be triggered by external electric fields. Here, we investigate the dielectric responses of ice VII to applied oscillating electric fields of various frequencies employing non-equilibrium molecular dynamics.

Water Breakup at FeO-Hematite/Water Interfaces: Influence of External Electric Fields from Nonequilibrium Molecular Dynamics.

The dynamical properties of physically and chemically adsorbed water molecules at pristine hematite-(001) surfaces have been studied by means of nonequilibrium molecular dynamics (NE-AIMD) in the ensemble at room temperature, in the presence of externally applied, uniform static electric fields of increasing intensity. The dissociation of water molecules to form chemically adsorbed species was scrutinized, in addition to charge redistribution and Grotthus proton hopping between water molecules. Dynamical properties of the adsorbed water molecules and OH and HO ions were gauged, such as the hydrogen bonds between protons in water molecules and the bridging oxygen atoms at the hematite surface, as well as the interactions between oxygen atoms in adsorbed water molecules and iron atoms at the hematite surface.

Dynamics of Meso-Chiral Interconversion in a Butterfly-Shape Overcrowded Alkene Rotor Tunable by Solvent Properties.

Elucidation of dynamics of molecular rotational motion is an essential part and challenging area of research. We demonstrate reversible diastereomeric interconversion of a molecular rotor composed of overcrowded butterfly-shape alkene (FDF). Its inherent dual rotatory motion (two rotors, one stator) with interconversion between two diastereomers, chiral trans-FDF and meso cis-FDF forms, has been examined in detail upon varying temperatures and solvents.

Amino-acid interactions with the Au(111) surface: adsorption, band alignment, and interfacial electronic coupling.

The charge transport properties of biological molecules like peptides and proteins are intensively studied for the great flexibility, redox-state variability, long-range efficiency, and biocompatibility of potential bioelectronic applications. Yet, the electronic interactions of biomolecules with solid metal surfaces, determining the conductivities of the biomolecular junctions, are hard to predict and usually unavailable. Here, we present accurate adsorption structures and energies, electronic band alignment, and interfacial electronic coupling data for all 20 natural amino acids computed using the DFT+Σ scheme based on the vdW-DF and OT-RSH functionals.

Coherent Electron Transport across a 3 nm Bioelectronic Junction Made of Multi-Heme Proteins.

Multi-heme cytochromes (MHCs) are fascinating proteins used by bacterial organisms to shuttle electrons within, between, and out of their cells. When placed in solid-state electronic junctions, MHCs support temperature-independent currents over several nanometers that are 3 orders of magnitude higher compared to other redox proteins of similar size. To gain molecular-level insight into their astonishingly high conductivities, we combine experimental photoemission spectroscopy with DFT+Σ current-voltage calculations on a representative Gold-MHC-Gold junction.

Possibility of realizing superionic ice VII in external electric fields of planetary bodies.

In a superionic (SI) ice phase, oxygen atoms remain crystallographically ordered while protons become fully diffusive as a result of intramolecular dissociation. Ice VII's importance as a potential candidate for a SI ice phase has been conjectured from anomalous proton diffusivity data. Theoretical studies indicate possible SI prevalence in large-planet mantles (e.

Ergodicity Breaking in Thermal Biological Electron Transfer? Cytochrome C Revisited II.

It was recently suggested that cytochrome c operates in an ergodicity-breaking regime characterized by unusually large energy gap thermal fluctuations and associated reorganization free energies for heme oxidation of up to 3.0 eV. The large fluctuations were reported to lower activation free energy for oxidation of the heme cofactor by almost a factor of 2 compared to the case where ergodicity is maintained.

Ergodicity-Breaking in Thermal Biological Electron Transfer? Cytochrome C Revisited.

It was recently suggested that certain redox proteins operate in an ergodicity-breaking regime to facilitate biological electron transfer (ET). A signature for this is a large variance reorganization free energy (several electronvolts) but a significantly smaller Stokes reorganization free energy due to incomplete protein relaxation on the time scale of the ET event. Here we investigate whether this picture holds for oxidation of cytochrome c in aqueous solution, at various levels of theory including classical molecular dynamics with two additive and one electronically polarizable force field, and QM/MM calculations with the QM region treated by full electrostatic DFT embedding and by the perturbed matrix method.

Multimodal switching of a redox-active macrocycle.

Molecules that can exist in multiple states with the possibility of toggling between those states based on different stimuli have potential for use in molecular switching or sensing applications. Multimodal chemical or photochemical oxidative switching of an antioxidant-substituted resorcinarene macrocycle is reported. Intramolecular charge-transfer states, involving hemiquinhydrones are probed and these interactions are used to construct an oxidation-state-coupled molecular switching manifold that reports its switch-state conformation via striking variation in its electronic absorption spectra.

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

The bacterium 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.

Adsorption of Amino Acids on Gold: Assessing the Accuracy of the GolP-CHARMM Force Field and Parametrization of Au-S Bonds.

The interaction of amino acids with metal electrodes plays a crucial role in bioelectrochemistry and the emerging field of bionanoelectronics. Here we present benchmark calculations of the adsorption structure and energy of all natural amino acids on Au(111) in vacuum using a van-der-Waals density functional (revPBE-vdW) that showed good performance on the S22 set of weakly bound dimers (mean relative unsigned error (MRUE) wrt CCSD(T)/CBS = 13.3%) and adsorption energies of small organic molecules on Au(111) (MRUE wrt experiment = 11.

Pressure dependence of structural properties of ice VII: An ab initio molecular-dynamics study.

The observed anomalous self-diffusivity of ice VII in the region of 10 GPa at ∼400 K has been suggested to arise from a change in proton-hopping mechanism involving a transition from ionic-defect-driven diffusivity to that dominated by diffusion of rotational defects. Here, we report ab initio molecular dynamics to study the structural, hydrogen bonding, electronic, vibrational, and Raman properties of ice VII at this temperature and between 5 and 20 GPa to elucidate any possible hints of intramolecular strain that may serve as precursor events for proton hopping to unfold. We determine such equilibrium properties to be in reasonable agreement with experimental Raman spectra, although we do not detect any water-dissociation and proton-hopping events per se, owing to still-large water-dissociation free-energy barriers.

NMR Spectroscopic Determination of Enantiomeric Excess Using Small Prochiral Molecules.

The use of chiral auxiliaries, which derivatize enantiomers to diastereomers, is an established technique for NMR spectroscopic analysis of chirality and enantiomeric excess ( ee). Here we report that some small prochiral molecules exhibit ee-dependent splitting of H NMR signals at room temperature based on acid/base interactions with chiral analytes, especially when either a chiral or prochiral acid contains a phenoxy group at the α-position of the carboxylic acid. As a representative case, the benzylamine (BA)/2-phenoxylpropionic acid (PPA) complex was comprehensively investigated by using various methods.

Study of hydrogen-molecule guests in type II clathrate hydrates using a force-matched potential model parameterised from ab initio molecular dynamics.

The force-matching method has been applied to parameterise an empirical potential model for water-water and water-hydrogen intermolecular interactions for use in clathrate-hydrate simulations containing hydrogen guest molecules. The underlying reference simulations constituted ab initio molecular dynamics (AIMD) of clathrate hydrates with various occupations of hydrogen-molecule guests. It is shown that the resultant model is able to reproduce AIMD-derived free-energy curves for the movement of a tagged hydrogen molecule between the water cages that make up the clathrate, thus giving us confidence in the model.

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 × 10 s.