Charge transfer through a cytochrome multiheme chain: Theory and simulation

We study sequential charge transfer within a chain of four heme cofactors located in the c-type cytochrome subunit of the photoreaction center of Rhodopseudomonas viridis from a theoretical perspective. Molecular dynamics simulations of the thermodynamic integration type are used to compute two key energies of Marcus' theory of charge transfer, the driving force ?G and the reorganization energy λ. Due to the small exposure of the cofactors to the solvent and to charged amino acids, the outer sphere contribution to the reorganization energy almost vanishes. Interheme effective electronic couplings are estimated using ab initio wave functions and a well-parameterized semiempirical scheme for long-range interactions. From the resulting charge transfer rates, we conclude that at most the two heme molecules closest to the membrane participate in a fast recharging of the photoreaction center, whereas the remaining hemes are likely to have a different function, such as intermediate electron storage. Finally, we suggest means to verify or falsify this hypothesis.     

A nonorthogonal tight-binding model for hydrocarbon molecules and nanostructures

In spirit of extended-Hückel approximations, we have developed a nonorthogonal tight-binding total energy model for hydrocarbons with only a few adjustable parameters. Our model reproduces the geometry structures, binding energies, on-site charge transfer and vibrational frequencies of a variety of hydrocarbon molecules reasonably well. Comparative calculations on carbon fullerenes and nanotubes using tight-binding model and density functional theory demonstrate the potential of applying this model to large scale simulations of carbon nanostructures.     

Crystal structure of cyanobacterial photosystem II at 3.0 A resolution: a closer look at the antenna system and the small membrane-intrinsic subunits.

Photosystem II (PSII) is a homodimeric protein-cofactor complex embedded in the thylakoid membrane that catalyses light-driven charge separation accompanied by the water splitting reaction during oxygenic photosynthesis. In the first part of this review, we describe the current state of the crystal structure at 3.0 A resolution of cyanobacterial PSII from Thermosynechococcus elongatus [B. Loll et al., Towards complete cofactor arrangement in the 3.0 A resolution structure of photosystem II, Nature 438 (2005) 1040-1044] with emphasis on the core antenna subunits CP43 and CP47 and the small membrane-intrinsic subunits. The second part describes first the general theory of optical spectra and excitation energy transfer and how the parameters of the theory can be obtained from the structural data. Next, structure-function relationships are discussed that were identified from stationary and time-resolved experiments and simulations of optical spectra and energy transfer processes.     

Protein control of electron transfer rates via polarization: molecular dynamics studies of rubredoxin

The protein matrix of an electron transfer protein creates an electrostatic environment for its redox site, which influences its electron transfer properties. Our studies of Fe-S proteins indicate that the protein is highly polarized around the redox site. Here, measures of deviations of the environmental electrostatic potential from a simple linear dielectric polarization response to the magnitude of the charge are proposed. In addition, a decomposition of the potential is proposed here to describe the apparent deviations from linearity, in which it is divided into a "permanent" component that is independent of the redox site charge and a dielectric component that linearly responds or polarizes to the charge. The nonlinearity measures and the decomposition were calculated for Clostridium pasteurianum rubredoxin from molecular dynamics simulations. The potential in rubredoxin is greater than expected from linear response theory, which implies it is a better electron acceptor than a redox site analog in a solvent with a dielectric constant equivalent to that of the protein. In addition, the potential in rubredoxin is described well by a permanent potential plus a linear response component. This permanent potential allows the protein matrix to create a favorable driving force with a low activation barrier for accepting electrons. The results here also suggest that the reduction potential of rubredoxin is determined mainly by the backbone and not the side chains, and that the redox site charge of rubredoxin may help to direct its folding.     

Theoretical investigations on Azotobacter vinelandii ferredoxin I: effects of electron transfer on protein dynamics

Structural, energetic, and dynamical studies of Azotobacter vinelandii ferredoxin I are presented for native and mutant forms. The protein contains two iron-sulfur clusters, one of which ([3Fe-4S]) is believed to play a central role in the electron-coupled proton transfer. Different charge sets for the [3Fe-4S] cluster in its reduced and oxidized state are calculated with broken symmetry ab initio density functional theory methods and used in molecular dynamics (MD) simulations. The validity of the ab initio calculations is assessed by comparing partially optimized structures of the [3Fe-4S] clusters with x-ray structures. Possible proton transfer pathways between the protein and the iron-sulfur cluster are examined by both MD simulations and ab initio calculations. The MD simulations identify three main-chain hydrogen atoms--HN(13), HN(14), and HN(16)--that are within H-bonding distance of the [3Fe-4S] cluster throughout the MD simulations. They could thus play a role in the proton transfer from the protein to the iron-sulfur cluster. By contrast, the HD2(15) atom of the Asp-15 is seldom close enough to the [3Fe-4S] cluster to transfer a proton. Poisson-Boltzmann calculations indicate that there is a low, but nonzero probability, that Asp-15 is protonated at pH 7; this is a requirement for it to serve as a proton donor. Ab initio calculations with a fragment model for the protein find similar behavior for the transfer of a proton from the OH of the protonated side chain and the main-chain NH of Asp-15. The existence of a stable salt bridge between Asp-15 and Lys-84 in the D15E mutant, versus its absence in the wild-type, has been suggested as the cause of the difference in the rate of proton transfer. Extensive MD simulations were done to test this idea; the results do not support the proposal. The present findings, together with the available data, serve as the basis for an alternative proposal for the mechanism of the coupled electron-proton transfer reaction in ferredoxin I.     

Bright solitary waves as charge transport in DNA: A variational approximation

Modeling energy and charge transfer in DNA has been a challenging issue because of many conformations DNA can take. Due to its simplicity, we propose a discrete variational approach to study the charge transfer mechanism in DNA based on the Holstein-Su-Schrieffer-Heeger model. It is shown that bright solitary waves may propagate through the DNA and the variational approximation provides explicit relations between experimental parameters and important characteristics of the waves such as amplitude, width, chirp and homogenous phase, and energy. Our analytical predictions are confirmed by intensive numerical simulations with a good accuracy.     

On the charge regulation of proteins

It is known that the overall charge of a protein can change as the molecule approaches a charged object like another protein or a cell membrane. We have formalized this mechanism using a statistical mechanical framework and show how this rather overlooked interaction increases the attraction between protein molecules. From the theory, we can identify a unique property, the protein charge capacitance, that contains all information needed to describe the charge regulation mechanism. The capacitance can be obtained from experiment or theory and is a function of pH, salt concentration, and the number of titrating residues. For a range of different protein molecules, we calculate the capacitance and demonstrate how it can be used to quantify the charge regulation interaction. With minimal effort, the derived formulas can be used to improve existing models by including a charge regulation term. Good agreement is found between theory, simulations, and experimental data.     

Proton transport in carbonic anhydrase: Insights from molecular simulation

This article reviews the insights gained from molecular simulations of human carbonic anhydrase II (HCA II) utilizing non-reactive and reactive force fields. The simulations with a reactive force field explore protein transfer and transport via Grotthuss shuttling, while the non-reactive simulations probe the larger conformational dynamics that underpin the various contributions to the rate-limiting proton transfer event. Specific attention is given to the orientational stability of the His64 group and the characteristics of the active site water cluster, in an effort to determine both of their impact on the maximal catalytic rate. The explicit proton transfer and transport events are described by the multistate empirical valence bond (MS-EVB) method, as are alternative pathways for the excess proton charge defect to enter/leave the active site. The simulation results are interpreted in light of experimental results on the wild-type enzyme and various site-specific mutations of HCA II in order to better elucidate the key factors that contribute to its exceptional efficiency.     

Effects of polyelectrolyte chain stiffness, charge mobility, and charge sequences on binding to proteins and micelles

The binding affinities of polyanions for bovine serum albumin in NaCl solutions from I = 0.01-0.6 M, were evaluated on the basis of the pH at the point of incipient binding, converting each such pH(c) value into a critical protein charge Zc. Analogous values of critical charge for mixed micelles were obtained as the cationic surfactant mole fraction Yc. The data were well fitted as Yc or Zc = KI a, and values of K and a were considered as a function of normalized polymer charge densities (tau), charge mobility, and chain stiffness. Binding increased with chain flexibility and charge mobility, as expected from simulations and theory. Complex effects of tau were related to intrapolyanion repulsions within micelle-bound loops (seen in the simulations) or negative protein domain-polyanion repulsions. The linearity of Zc with radicalI at I < 0.3 M was explained by using protein electrostatic images, showing that Zc at I < 0.3 M depends on a single positive "patch"; the appearance of multiple positive domains I > 0.3 M (lower pH(c)) disrupts this simple behavior.     

Biomolecular simulations at constant pH

Like temperature and pressure, the solution pH is an important thermodynamic variable that is commonly varied in experiments and is used by cells to influence biochemical function. It is now becoming feasible to carry out practical molecular dynamics simulations that mimic the thermodynamics of such experiments, by allowing proton transfer between the system of interest and a hypothetical bath of protons at a given pH. These are demanding calculations, because the energetics of charge changes upon protonation or deprotonation must be accurately modeled, and because such simulations must sample both molecular configurations and the large number of protonation states that are possible for a molecule with many titrating sites.     

Theoretical study of DNA damage recognition via electron transfer from the [4Fe-4S] complex of MutY

The mechanism of site-specific recognition of DNA by proteins has been a long-standing issue. The DNA glycosylase MutY, for instance, must find the rare 8-oxoguanine-adenine mismatches among the large number of basepairs in the DNA. This protein has a [4Fe-4S] cluster, which is highly conserved in species as diverse as Escherichia Coli and Homo sapiens. The mixed-valent nature of this cluster suggests that charge transfer may play a role in MutY's function. We have studied the energetics of the charge transfer in Bacillus stearothermophilus MutY-DNA complex using multiscale calculation including density functional theory and molecular dynamics. The [4Fe-4S] cluster in MutY is found to undergo 2+ to 3+ oxidation when coupling to DNA through hole transfer, especially when MutY is near an oxoguanine modified base (oxoG). Employing the Marcus theory for electron transfer, we find near optimal Frank-Condon factors for electron transfer from MutY to oxoguanine modified base. MutY has modest selectivity for oxoguanine over guanine due to the difference in oxidation potential. The tunneling matrix element is significantly reduced with the mutation R149W, whereas the mutation L154F reduces the tunneling matrix element as well as the Frank-Condon factor. Both L154F and R149W mutations are known to dramatically reduce or eliminate repair efficiency. We suggest a scenario where the charge transfer leads to a stabilization of the specific binding conformation, which is likely the recognition mode, thus enabling it to find the damaged site efficiently.     

The mechanism of the proton transfer: an outline

A brief summary of the principal notions of the quantum-mechanical theory of the charge transfer reactions has been presented. In the framework of this theory, the mechanism of the proton transfer consists in the classical medium reorganization that equalizes the proton energy levels in the initial and final states, and a consequent proton transfer via a quantum-mechanical underbarrier transition. On the basis of this mechanism, factors influencing the proton transfer probability, and hence kinetic isotope effect, have been discussed; among them are the optimum tunneling distance, the involvement of the excited vibrational states, etc. Semi-classical and quantum-mechanical treatments of the Swain-Schaad relations have been compared. Some applications to enzymatic proton-transfer reactions have been described.     

Importance of polarization effect in the study of metalloproteins: Application of polarized protein specific charge scheme in predicting the reduction potential of azurin

Molecular dynamics (MD) simulation is commonly used in the study of protein dynamics, and in recent years, the extension of MD simulation to the study of metalloproteins is gaining much interest. Choice of force field is crucial in MD studies, and the inclusion of metal centers complicates the process of accurately describing the electrostatic environment that surrounds the redox centre. Herein, we would like to explore the importance of including electrostatic contribution from both protein and solvent in the study of metalloproteins. MD simulations with the implementation of thermodynamic integration will be conducted to model the reduction process of azurin from Pseudomonas aeruginosa. Three charge schemes will be used to derive the partial charges of azurin. These charge schemes differ in terms of the amount of immediate environment, respective to copper, considered during charge fitting, which ranges from the inclusion of copper and residues in the first coordination sphere during density functional theory charge fitting to the comprehensive inclusion of protein and solvent effect surrounding the metal centre using polarized protein‐specific charge scheme. From the simulations conducted, the relative reduction potential of the mutated azurins respective to that of wild‐type azurin (ΔE_cal) were calculated and compared with experimental values. The ΔE_cal approached experimental value with increasing consideration of environmental effect hence substantiating the importance of polarization effect in the study of metalloproteins. This study also attests the practicality of polarized protein‐specific charge as a computational tool capable of incorporating both protein environment and solvent effect into MD simulations. Proteins 2014; 82:2209–2219. © 2014 Wiley Periodicals, Inc.     

Changing the charge distribution of beta-helical-based nanostructures can provide the conditions for charge transfer

In this work we present a computational approach to the design of nanostructures made of structural motifs taken from left-handed beta-helical proteins. Previously, we suggested a structural model based on the self-assembly of motifs taken from Escherichia coli galactoside acetyltransferase (Protein Data Bank 1krr, chain A, residues 131-165, denoted krr1), which produced a very stable nanotube in molecular dynamics simulations. Here we modify this model by changing the charge distribution in the inner core of the system and testing the effect of this change on the structural arrangement of the construct. Our results demonstrate that it is possible to generate the proper conditions for charge transfer inside nanotubes based on assemblies of krr1 segment. The electronic transfer would be achieved by introducing different histidine ionization states in selected positions of the internal core of the construct, in addition to specific mutations with charged amino acids that altogether will allow the formation of coherent networks of aromatic ring stacking, salt-bridges, and hydrogen bonds.     

Electrochromic shift of chlorophyll absorption in photosystem I from Synechocystis sp. PCC 6803: a probe of optical and dielectric properties around the secondary electron acceptor

Nanosecond absorption dynamics at approximately 685 nm after excitation of photosystem I (PS I) from Synechocystis sp. PCC 6803 is consistent with electrochromic shift of absorption bands of the Chl a pigments in the vicinity of the secondary electron acceptor A(1). Based on experimental optical data and structure-based simulations, the effective local dielectric constant has been estimated to be between 3 and 20, which suggests that electron transfer in PS I is accompanied by considerable protein relaxation. Similar effective dielectric constant values have been previously observed for the bacterial photosynthetic reaction center and indicate that protein reorganization leading to effective charge screening may be a necessary structural property of proteins that facilitate the charge transfer function. The data presented here also argue against attributing redmost absorption in PS I to closely spaced antenna chlorophylls (Chls) A38 and A39, and suggest that optical transitions of these Chls, along with that of connecting chlorophyll (A40) lie in the range 680-695 nm.     

Synthesis, crystal structure, electronic structure, bonding, photoluminescence and spectroscopic property investigations of a mononuclear 1,10-phenanthroline and 5-bromo-salicylate ternary indium(III) complex

The synthesis, X-ray structure, electronic structure, bonding, photoluminescence, spectroscopic property and characterization of an indium(III) complex, [In(Hbsac)₃(phen)] (1) (H₂bsac = 5-bromo-salicylic acid, and phen = 1,10-phenanthroline) are presented. Complex 1 is octacoordinate and carboxylate chelating, being novel and rarely reported for main group complexes. The electronic structure, bonding and the charge transfer properties of light excitation and light emission are discussed in detail using first-principles theory, including partial density of states (PDOSs), crystal orbital overlap population (COOP), the density functional theory (DFT/TDDFT) analysis schemes. The charge transfer is mainly π → π^∗ intraligand charge transfer transition (ILCT) for excitation, and π → π^∗ ligand-to-ligand charge transfer transition (LL′CT) for emission in nature.