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. For these applications, semi-empirical approaches such as the perturbed matrix method (PMM) have been developed and successfully used to study charge-transfer processes in biomolecules. Here, we explore the performance of PMM on prototypical redox-active protein azurin in various environments, from solution to vacuum interfaces with gold surfaces and protein junction. We systematically benchmarked the robustness and convergence of the method with respect to the quantum-centre size, size of the Hamiltonian, number of samples, and level of theory. We show that PMM can adequately capture all the trends associated with the structural and electronic changes related to azurin oxidation at bio/metallic interfaces.

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. The support of computational chemistry methods which appropriately complement the interpretation framework of experimental results is also important. This text describes recent directions in electrochemical methods for the determination of proteins and briefly summarizes available methodologies for the selective labeling of proteins using redox-active probes. Attention is also paid to the theoretical aspects of electron transport and the effect of an external electric field on the structure of selected proteins. Instead of providing a comprehensive overview, we aim to highlight areas of interest that have not been summarized recently, but, at the same time, represent current trends in the field.

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.e., in aqueous solution, the reorganization free energies of dry proteins or proteins adsorbed to metal surfaces remain unknown. Here, we investigate the redox properties of blue copper protein azurin, a prototypical redox-active metalloprotein previously probed by various experimental techniques both in solution and on metal/vacuum interfaces. We used a hybrid quantum mechanical/molecular mechanical computational technique based on density functional theory to explore protein dynamics, flexibility, and corresponding reorganization free energies in aqueous solution, vacuum, and on vacuum gold interfaces. Surprisingly, the reorganization free energy only slightly decreases when azurin is dried because the loss of the hydration shell leads to larger flexibility of the protein near its redox site. At the vacuum gold surfaces, the energetics of the structure relaxation depends on the adsorption geometry; however, significant reduction of the reorganization free energy was not observed. These findings have important consequences for the charge transport mechanism in vacuum devices, showing that the free energy barriers for protein oxidation remain significant even under ultra-high vacuum conditions.

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.

Adsorption of Hexavalent Chromium Using Activated Carbon Produced from Sargassum 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. Several techniques (nitrogen adsorption, pHPZC, Boehm titration, FTIR and XPS) were used to characterize the physicochemical properties of the activated carbons. The SAC600 3/1 was predominantly microporous and mesoporous (39.6% and 60.4%, respectively) and revealed a high specific surface area (1695 m2·g-1). To serve as a comparison element, a commercial reference activated carbon with a large specific surface area (1900 m2·g-1) was also investigated. The influence of several parameters on the adsorption capacity of AC was studied: solution pH, solution temperature, contact time and Cr(VI) concentration. The best adsorption capacities were found at very acid (pH 2) solution pH and at lower temperatures. The adsorption kinetics of SAC600 3/1 fitted well a pseudo-second-order type 1 model and the adsorption isotherm was better described by a Jovanovic-Freundlich isotherm model. Molecular dynamics (MD) simulations confirmed the experimental results and determined that hydroxyl and carboxylate groups are the most influential functional groups in the adsorption process of chromium anions. MD simulations also showed that the addition of MgCl2 to the activated carbon surface before adsorption experiments, slightly increases the adsorption of HCrO4- and CrO42- anions. Finally, this theoretical study was experimentally validated obtaining an increase of 5.6% in chromium uptake.

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. For comparison, data obtained using the popular PBE functional are provided as well. Tryptophan, compared to other amino acids, is shown to be distinctly exceptional in terms of the electronic properties related to charge transport. Its high adsorption energy, frontier-orbital levels aligned relatively close to the Fermi energy of gold and strong interfacial electronic coupling make it an ideal candidate for facilitating charge transfer on such heterogeneous interfaces. Although the amino acids in peptides and proteins are affected by the structural interactions hindering their contact with the surface, knowledge of the single-molecule surface interactions is necessary for a detailed understanding of such structural effects and tuning of potential applications.

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 ab initio molecular dynamics. We focus on the dynamical properties of a dipole-ordered ice VII structure, for which we explored external-field-induced electronic polarisation and the vibrational spectral density of states (VDOS). These analyses are important for the understanding of collective motions in the ice-VII lattice and the electronic properties of this exotic water phase.

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. Electronic couplings are largest for cofacial dimers, in particular, sulfur-containing polyaromatic hydrocarbons, with values in excess of 0.5 eV, followed by parallel displaced cofacial dimers. V-shaped dimer motifs, often encountered in the herringbone layers of organic crystals, exhibit medium-sized couplings, whereas T-shaped dimers have the lowest couplings. DFT values obtained from the projector operator-based diabatization (POD) method are initially benchmarked against the smaller databases HAB11 (HAB7-) and found to systematically improve when climbing Jacob's ladder, giving mean relative unsigned errors (MRUEs) of 27.7% (26.3%) for the generalized gradient approximation (GGA) functional BLYP, 20.7% (15.8%) for hybrid functional B3LYP, and 5.2% (7.5%) for the long-range corrected hybrid functional omega-B97X. Cost-effective POD in combination with a GGA functional and very efficient DFTB calculations on the dimers of the HAB79 database give a good linear correlation with the CASSCF/NEVPT2 reference data, which, after scaling with a multiplicative constant, gives reasonably small MRUEs of 17.9% and 40.1%, respectively, bearing in mind that couplings in HAB79 vary over 4 orders of magnitude. The ab initio reference data reported here are expected to be useful for benchmarking other DFT or semi-empirical approaches for electronic coupling calculations.

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. The free energy profile of 180° revolution of one rotor part has a bimodal shape with unevenly positioned maxima (transition states). FDF in aromatic solvents adopts preferentially meso cis-conformation, while in non-aromatic solvents a chiral trans-conformation is more abundant owing to the solvent interactions with peripheral hexyl chains (solvophobic effect). Moderate correlations between the trans-FDF/cis-FDF ratio and solvent parameters, such as refractive index, polarizability, and viscosity were found.

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.

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. Furthermore, with the aid of an umbrella-sampling algorithm, we calculate barrier heights for the force-matched model, yielding the free-energy barrier for a tagged molecule to move between cages. The barrier heights are reasonably large, being on the order of 30 kJ/mol, and are consistent with our previous studies with empirical models [C. J. Burnham and N. J. English, J. Phys. Chem. C 120, 16561 (2016) and C. J. Burnham et al., Phys. Chem. Chem. Phys. 19, 717 (2017)]. Our results are in opposition to the literature, which claims that this system may have very low barrier heights. We also compare results to that using the more ad hoc empirical model of Alavi et al. [J. Chem. Phys. 123, 024507 (2005)] and find that this model does very well when judged against the force-matched and ab initio simulation data.

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.

Communication: Influence of external static and alternating electric fields on water from long-time non-equilibrium ab initio molecular dynamics.

The response of water to externally applied electric fields is of central relevance in the modern world, where many extraneous electric fields are ubiquitous. Historically, the application of external fields in non-equilibrium molecular dynamics has been restricted, by and large, to relatively inexpensive, more or less sophisticated, empirical models. Here, we report long-time non-equilibrium ab initio molecular dynamics in both static and oscillating (time-dependent) external electric fields, therefore opening up a new vista in rigorous studies of electric-field effects on dynamical systems with the full arsenal of electronic-structure methods. In so doing, we apply this to liquid water with state-of-the-art non-local treatment of dispersion, and we compute a range of field effects on structural and dynamical properties, such as diffusivities and hydrogen-bond kinetics.

Hydrogen-bond dynamics at the bio-water interface in hydrated proteins: a molecular-dynamics study.

Water is fundamental to the biochemistry of enzymes. It is well known that without a minimum amount of water, enzymes are not biologically active. Bare minimal solvation for biological function corresponds to about a single layer of water covering enzymes' surfaces. Many contradictory studies on protein-hydration-water-coupled dynamics have been published in recent decades. Following prevailing wisdom, a dynamical crossover in hydration water (at around 220 K for hydrated lysozymes) can trigger larger-amplitude motions of the protein, activating, in turn, biological functions. Here, we present a molecular-dynamics-simulation study on a solvated model protein (hen egg-white lysozyme), in which we determine, inter alia, the relaxation dynamics of the hydrogen-bond network between the protein and its hydration water molecules on a residue-per-residue basis. Hydrogen-bond breakage/formation kinetics is rather heterogeneous in temperature dependence (due to the heterogeneity of the free-energy surface), and is driven by the magnitude of thermal motions of various different protein residues which provide enough thermal energy to overcome energy barriers to rupture their respective hydrogen bonds with water. In particular, arginine residues exhibit the highest number of such hydrogen bonds at low temperatures, losing almost completely such bonding above 230 K. This suggests that hydration water's dynamical crossover, observed experimentally for hydrated lysozymes at ∼220 K, lies not at the origin of the protein residues' larger-amplitude motions, but rather arises as a consequence thereof. This highlights the need for new experimental investigations, and new interpretations to link protein dynamics to functions, in the context of key interrelationships with the solvation layer.

Quantum and classical inter-cage hopping of hydrogen molecules in clathrate hydrate: temperature and cage-occupation effects.

Building on our previous work (J. Phys. Chem. C, 2016, 120, 16561), using an empirical model we run both classical and path-integral molecular dynamics simulations for a type II clathrate hydrate containing different amounts of guest H2 molecules from 1 to 5 molecules per large cage, with results presented at temperatures of 50, 100 K and 200 K. We present results for the density isosurfaces of the guest molecules at all different occupations and temperatures, showing how the density approaches the perfect tetrahedral structure which has been found for the n = 4 case in which each molecule sits on the vertex of a tetrahedron about the centre of each large cage. We calculate free-energy profiles of the molecules over the volume interior to the cage, and using umbrella sampling, we also calculate the free energy barrier for the molecule to hop between cages. We show that this barrier reduces almost linearly for n = 1-3 molecules per large cage, but becomes larger than would be expected (from extrapolation) for the n = 4 case, with this departure from linearity becoming larger at lower temperatures. We show that, perhaps counter-intuitively, these barriers tend to increase with raising the temperature, and also counter-intuitively that quantisation of the nuclei acts to increase the barriers. Finally, for the n = 4 case, a comparison is made between the empirical model results and those from an ab initio molecular dynamics calculation, which shows that qualitative agreement exists between the two models.

Oscillating electric-field effects on adsorbed-water at rutile- and anatase-TiO2 surfaces.

We have performed non-equilibrium molecular dynamics simulations of various TiO2/water interfaces at ambient temperature in presence of oscillating electric fields in frequency range 20-100 GHz and RMS intensities 0.05-0.25 V/Å. Although the externally applied fields are by one order of magnitude lower than the intrinsic electric field present on the interfaces (∼1.5-4.5 V/Å), significant non-thermal coupling of rotational and translational motion of water molecules was clearly observed. Enhancement of the motion, manifested by increase of diffusivity, was detected in the first hydration layer, which is known to be heavily confined by adsorption to the TiO2 surface. Interestingly, the diffusivity increases more rapidly on anatase than on rutile facets where the adsorbed water was found to be more organized and restrained. We observed that the applied oscillating field reduces number of hydrogen bonds on the interface. The remaining H-bonds are weaker than those detected under zero-field conditions; however, their lifetime increases on most of the surfaces when the low-frequency fields are applied. Reduction of adsorption interaction was observed also in IR spectra of interfacial water where the directional patterns are smeared as the intensities of applied fields increase.

Perturbation of hydration layer in solvated proteins by external electric and electromagnetic fields: Insights from non-equilibrium molecular dynamics.

Given the fundamental role of water in governing the biochemistry of enzymes, and in regulating their wider biological activity (e.g., by local water concentration surrounding biomolecules), the influence of extraneous electric and electromagnetic (e/m) fields thereon is of central relevance to biophysics and, more widely, biology. With the increase in levels of local and atmospheric microwave-frequency radiation present in modern life, as well as other electric-field exposure, the impact upon hydration-water layers surrounding proteins, and biomolecules generally, becomes a particularly pertinent issue. Here, we present a (non-equilibrium) molecular-dynamics-simulation study on a model protein (hen egg-white lysozyme) hydrated in water, in which we determine, inter alia, translational self-diffusivities for both hen egg-white lysozyme and its hydration layer together with relaxation dynamics of the hydrogen-bond network between the protein and its hydration-layer water molecules on a residue-per-residue basis. Crucially, we perform this analysis both above and below the dynamical-transition temperature (at ∼220 K), at 300 and 200 K, respectively, and we compare the effects of external static-electric and e/m fields with linear-response-régime (r.m.s.) intensities of 0.02 V/Å. It was found that the translational self-diffusivity of hen egg-white lysozyme and its hydration-water layer are increased substantially in static fields, primarily due to the induced electrophoretic motion, whilst the water-protein hydrogen-bond-network-rearrangement kinetics can also undergo rather striking accelerations, primarily due to the enhancement of a larger-amplitude local translational and rotational motion by charged and dipolar residues, which serves to promote hydrogen-bond breakage and re-formation kinetics. These external-field effects are particularly evident at 200 K, where they serve to induce the protein- and solvation-layer-response effects redolent of dynamical transition at a lower temperature (∼200 K) vis-à-vis the zero-field case (∼220 K).

Chiral guest binding as a probe of macrocycle dynamics and tautomerism in a conjugated tetrapyrrole.

We report chiral guest binding as a probe of prototropic tautomerism and macrocyclic inversion in a highly conjugated tetrapyrrole studied using (1)H NMR spectroscopy in conjunction with mandelic acid as the chiral guest. Both tautomerism and macrocycle inversion can be influenced in a non-trivial way depending on temperature and the respective concentrations of tetrapyrrole host, chiral guest or water. Chirality of the interacting guest is the key feature since it permits separation and detailed observation of macrocyclic inversion and tautomerism. Based on this, a methodology was developed to identify and characterize the dynamic processes. Our observations suggest that yields of products (e.g., of asymmetric reactions) can be affected by reactivity of functional groups (in molecules undergoing tautomerism or inversion) by varying solution properties including reagent concentrations and impurities such as water. This work establishes a connection between the important chemical concepts of chirality, tautomerism, and macrocyclic dynamics.

Reaction mechanism of Ru(II) piano-stool complexes: umbrella sampling QM/MM MD study.

Biologically relevant interactions of piano-stool ruthenium(II) complexes with ds-DNA are studied in this article by hybrid quantum mechanics-molecular mechanics (QM/MM) computational technique. The whole reaction mechanism is divided into three phases: (i) hydration of the [Ru(II) (η(6) -benzene)(en)Cl](+) complex, (ii) monoadduct formation between the resulting aqua-Ru(II) complex and N7 position of one of the guanines in the ds-DNA oligomer, and (iii) formation of the intrastrand Ru(II) bridge (cross-link) between two adjacent guanines. Free energy profiles of all the reactions are explored by QM/MM MD umbrella sampling approach where the Ru(II) complex and two guanines represent a quantum core, which is described by density functional theory methods. The combined QM/MM scheme is realized by our own software, which was developed to couple several quantum chemical programs (in this study Gaussian 09) and Amber 11 package. Calculated free energy barriers of the both ruthenium hydration and Ru(II)-N7(G) DNA binding process are in good agreement with experimentally measured rate constants. Then, this method was used to study the possibility of cross-link formation. One feasible pathway leading to Ru(II) guanine-guanine cross-link with synchronous releasing of the benzene ligand is predicted. The cross-linking is an exergonic process with the energy barrier lower than for the monoadduct reaction of Ru(II) complex with ds-DNA.