Electron Tunneling In Proteins Research Articles

Distance Dependence of Electron Transfer through Conformationally Constrained Peptides

Understanding and the ability of peptides to mediate long-range electron tunneling in proteins is an evergreen topic. In this context, the study of electron transfer (ET) through model peptides has been particularly useful, especially to assess the occurrence (or competition) of the superexchange and sequential hopping mechanisms as a function of the structure and length of the peptide bridge. In previous studies [1,2], we stressed the importance of dealing with peptides with a well-defined and rigid structure to properly correlate kinetic and structural data. This structural control was made possible by using model peptide bridges based on oligomers of the α-aminoisobutyric acid (Aib) residue. The Aib unit is characterized by a marked steric hindrance at the α-carbon, and this allows the preparation of very rigid peptides. Rigidity is ensured by a framework of intramolecular C=O···H-N hydrogen bonds. Consequently, these peptides possess a strong dipole moment along the main axis [3]. In previous studies, we used cyclic voltammetry to study the dissociative ETs in two series of Donor − Aib-peptide − Acceptor systems in which we changed the donor group, whereas the acceptor was kept constant (a dialkyl peroxide moiety, resulting in the cleavage of the O-O peroxide bond [4]). In this communication, we describe the outcome of dissociative ETs carried out using a new series of Donor − Aib-peptide − Acceptor system in which the acceptor was a perbenzoate moiety [5]. This change also affects the dissociative ET driving force. The same peptide-length dependent dissociative ETs were tested for a possible solvent effect.

Quantum effects in biological electron transfer

Over recent decades, quantum effects such as coherent electronic energy transfers, electron and hydrogen tunneling have been uncovered in biological processes. In this Perspective, we highlight some of the main conceptual and methodological tools employed in the field to investigate electron tunneling in proteins, with a particular emphasis on the methodologies we are currently developing. In particular, we describe our recent contributions to the development of a mixed quantum-classical framework aimed at describing physical systems lying at the border between the quantum and semi-classical worlds. We present original results obtained by combining our approach with constrained Density Functional Theory calculations. Moving to coarser levels of description, we summarize our latest findings on electron transfer between two redox proteins, thereby showing the stabilization of inter-protein, water-mediated, electron-transfer pathways.

First principles studies of electron tunneling in proteins

A first principles study of electronic tunneling along the chain of seven Fe/S clusters in respiratory complex I, a key enzyme in the respiratory electron transport chain, is described. The broken-symmetry states of the Fe/S metal clusters calculated at both DFT and semi-empirical ZINDO levels were utilized to examine both the extremely weak electronic couplings between Fe/S clusters and the tunneling pathways, which provide a detailed atomistic-level description of the charge transfer process in the protein. One-electron tunneling approximation was found to hold within a reasonable accuracy, with only a moderate induced polarization of the core electrons. The method is demonstrated to be able to calculate accurately the coupling matrix elements as small as 10 −4 cm −1. A distinct signature of the wave properties of electrons is observed as quantum interferences of multiple tunneling pathways.

Long-Distance Electron Tunneling in Proteins: A New Challenge for Time-Resolved Spectroscopy.

Long-distance electron tunneling is a fundamental process which is involved in energy generation in cells. The tunneling occurs between the metal centers in the respiratory enzymes, typically over distances up to 20 or 30 Å. For such distances, the tunneling time-i.e., the time during which an electron passes through the body of the protein molecule from one metal center to another-is of the order of 10 fs. Here the process of electron tunneling in proteins is reviewed, and a possibility of experimental observation of real-time electron tunneling in a single protein molecule is discussed.

The Direct Electron Transfer of Myoglobin Based on the Electron Tunneling in Proteins

The electron tunneling of the protein-polypeptide interactions was observed in the study of direct electron transfer of the myoglobin (Mb) on the electrode surface. The Mb was selected as a redox active protein and gelatine was selected to couple with Mb to form an electron tunneling. The electrochemical results indicated the presence of the electron tunneling and the direct electron transfer. The circular dichroism spectra suggested that the beta-sheet chain of gelatine could interact with alpha-helical chain to form an electron tunneling to promote the protein direct electrochemistry. The SDS-PAGE results proved that the electron tunneling between Mb and gelatine was noncovalent hydrogen bonds. The immobilized Mb showed a couple of quasi-reversible redox peaks with a formal potential of -0.37V (vs SCE) in 0.1 M pH 7.0 PBS. The modified electrodes displayed a rapid amperometric response to the reduction of oxygen, H2O2, and nitrite.

Does internal water influence electron tunneling in proteins? Example of cytochrome c oxidase

AbstractIn a recent study, the internal electron transfer in bovine heart cytochrome c oxidase (CcO) was examined using the tunneling currents method at the extended Hückel level of electronic structure. No internal water was present in the published structure of the enzyme, and none was taken into account in the calculations. Through computer simulation, we recently found an intriguing water hydrogen bond network in the vicinity of CcO catalytic site and in the region of electron tunneling. In this work, we reexamine the problem, with the focus on the possibility of the influence of water on electron transfer process. The calculations are carried out with the tunneling currents method implemented using more accurate ZINDO/S quantum chemical model. Results for the electron transfer from heme a to heme a3, a key step in the function of the enzyme, are presented. With molecular dynamics simulations, we identify configurations in which the water molecules interfere with the tunneling pathway. The tunneling matrix element is evaluated by the flux theorem of the tunneling currents method, and is found to be 0.34 cm−1 in the “dry” system and 1.38 cm−1 in the “wet” system. The analysis of the tunneling flux indicates that the impact of water is localized on Phe377 and spread to the methyl group and to His376, both on the heme a3 side of the ET pathway. The increase of the tunneling coupling by a factor of 4 in this case demonstrates that internal water in proteins can influence ET rate in proteins by as much as an order of magnitude. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005

Exploring the electronic and mechanical properties of protein using conducting atomic force microscopy.

In interfacing man-made electronic components with specifically folded biomacromolecules, the perturbative effects of junction structure on any signal generated should be considered. We report herein on the electron-transfer characteristics of the blue copper metalloprotein, azurin, as characterized at a refined level by conducting atomic force microscopy (C-AFM). Specifically, the modulation of current-voltage (I-V) behavior with compressional force has been examined. In the absence of assignable resonant electron tunneling within the confined bias region, from -1 to 1 V, the I-V behavior was analyzed with a modified Simmons formula. To interpret the variation of tunneling barrier height and barrier length obtained by fitting with the modified Simmons formula, an atom packing density model associated with protein mechanical deformation was proposed and simulated by molecular dynamics. The barrier heights determined at the minimum forces necessary for stable electrical contact correlate reasonably well with those estimated from bulk biophysical (electroanalytical and photochemical) experiments previously reported. At higher forces, the tunnel barrier decreases to fall within the range observed with saturated organic systems. Molecular dynamics simulations revealed changes in secondary structure and atomic density of the protein with respect to compression. At low compression, where transport measurements are made, secondary structure is retained, and atomic packing density is observed to increase linearly with force. These predictions, and those made at higher compression, are consistent with both experimentally observed modulations of tunneling barrier height with applied force and the applicability of the atom packing density model of electron tunneling in proteins to molecular-level analyses.

Long-distance electron tunneling in proteins

Long-distance tunneling is the major mechanism of electron transfer (ET) in proteins. For a number of years, a major question has been whether specific electron tunneling pathways exist. This question is still debated in the literature, because the pathways are not observed directly, and interpretation of experimental results on ET rates involves ambiguities. The extremely small tunneling interactions are difficult to calculate accurately. Recently, there has been remarkable progress in the area; however, some problems still remain unresolved. The accurate prediction of the absolute rates of long-distance ET reactions and other biological charge-transfer reactions is a particularly pressing issue. The current theoretical calculations indicate that the specific paths do exist in static protein structures. However, the protein motions can result in significant averaging of the spatial tunneling patterns, and it is not clear how accurately subtle quantum interference effects are described by the present theories. The key to resolving these issues is to perform accurate, first-principles calculations of electron tunneling that include the dynamics of the protein. This paper reviews some of theoretical issues of electron tunneling dynamics in inhomogeneous organic media.

Long-distance electron tunneling in proteins

Long-distance electron tunneling in proteins

Electron Tunneling in Proteins: Implementation of ZINDO Model for Tunneling Currents Calculations

The tunneling currents method developed previously by this group for the description of electron tunneling in proteins and other complex molecular structures is implemented at the semiempirical ZINDO level. This implementation bridges the gap between fully ab initio and simple one electron methods, such as the extended Huckel method, which has been previously employed in tunneling studies, and allows for accurate calculations to be performed on realistic large protein systems with only a moderate effort. One additional advantage of this method is that it employs the STO basis functions, which decay more slowly than do GTO functions, so that the weak tunneling interactions of noncovalently bonded atoms of the protein can be accounted for with a minimum basis set. Numerical results are demonstrated on the polypeptide chain (His) 2 (Met)Cu 1 + -(Cys)-(Gly 5 )-(His)Ru 3 (bpy 2 )Im, which models the Ru-modified azurin charge transfer system studied by Gray and co-workers.

Worm Model for Electron Tunneling in Proteins: Consolidation of the Pathway Model and the Dutton Plot

We present a novel method for selecting important electron tunneling pathways in proteins by connecting important interatomic tunneling currents. Then, we constituted an electron tunneling route, called a “worm”, which is formed by averaging over all of the interatomic tunneling currents. The method is applied to six kinds of Ru-modified azurins where the electron transfer takes place from the copper ion to the ruthenium ion linked to the surface of the azurin. We found that the worm is not straight but winds, reflecting the specific role of the microenvironment of the protein structure and ligands in the electron tunneling pathway and rather narrow radius of the worm, ca. 1.5 A at most. The donor−acceptor distance dependence of the electron-transfer rate ke is examined by taking into account the one-dimensional atomic density in the worm. We found that the Dutton plot, in which the logarithm of ke is in a linear relation with the donor−acceptor distance, which, in turn, depends somewhat on the one-dimens...

Electron Tunneling in Quasi-One-Dimensional Resonant Molecular Systems. Ab Initio Study

The method of tunneling currents is applied for study of electron-tunneling dynamics in quasi-one-dimensional donor−bridge−acceptor systems in which the bridge is composed of a sequence of atoms located on a straight line connecting donor and acceptor complexes. Such a system provides a simple model for the description of electronic processes in molecular wires. Of our particular interest are the following questions: how exactly does an electron tunnel through an atom or a molecule, and what is the precise meaning of “through-bond” and “through-space” tunneling, the concepts frequently used in the description of electron tunneling in proteins. Our method consists of an ab initio electronic structure calculation of the spatial distribution of tunneling currents occurring during the tunneling transition in the system, when an electron tunnels from the one end of molecular wire to the other. The analysis is based on calculation of two diabatic electronic states corresponding to localization of a tunneling electron on donor and acceptor sites, respectively. All electrons in the system are taken into account at the Hartree−Fock level, and as such the method allows us to examine the reaction of the valence electrons on the bridge to the tunneling charge. The symmetry of the chosen system allows a relatively simple way for a complete and detailed analysis of the spatial distribution of the currents in the system. These results provide new insights into the nature of long-distance electron tunneling in organic media.

Electron tunneling in proteins: role of the intervening medium

Analysis of electron-transfer (ET) kinetics data obtained from experiments on Ru-modified proteins (cytochrome c, azurin, myoglobin) reveals that distant donor-acceptor electronic couplings depend upon the secondary structure of the intervening polypeptide matrix. Rates of Fe2+→Ru3+ ET reactions in cytochrome c decay exponentially with tunneling-pathway length (decay constant 0.73 A–1); these rates also decay exponentially with Ru-Fe distance (decay constant 1.1 A–1). In azurin, a β-sheet protein, Cu+→Ru3+ rates exhibit an exponential Cu-Ru distance dependence with a decay constant of 1.1 A–1. Comparison of distant couplings in azurin and myoglobin suggests that hydrogen bonds are better mediators across β sheets than through α helices.

Tunneling currents in electron transfer reaction in proteins. II. Calculation of electronic superexchange matrix element and tunneling currents using nonorthogonal basis sets

In this paper we further develop the concept of interatomic tunneling currents [A.A. Stuchebrukhov, J. Chem. Phys. 104, 8424 (1996)] for the description of long-range electron tunneling in proteins. Here we discuss a formulation of the theory for the case when nonorthogonality of the atomic basis set of the medium propagating electron is explicitly taken into account. This method provides an effective computational scheme for an exact, i.e., nonperturbative, evaluation (in one-electron approximation) of the superexchange electron tunneling matrix element, and allows one to determine which regions in the protein matrix are important for the tunneling process. The theory is applied for calculation of tunneling currents and the electronic matrix element in His126-Ru-modified blue copper protein azurin from a recent experimental work of Gray and co-workers. Analysis of interatomic currents reveals a nontrivial structure of the tunneling flow between donor and acceptor in the intervening protein medium in this system.

Electron tunneling in proteins: role of the intervening medium

Electron tunneling in proteins: role of the intervening medium

Electron tunneling through covalent and noncovalent pathways in proteins

A model is presented for electron tunneling in proteins which allows the donor–acceptor interaction to be mediated by the covalent bonds between amino acids and noncovalent contacts between amino acid chains. The important tunneling pathways are predicted to include mostly bonded groups with less favorable nonbonded interactions being important when the through bond pathway is prohibitively long. In some cases, vibrational motion of nonbonded groups along the tunneling pathway strongly inluences the temperature dependence of the rate. Quantitative estimates for the sizes of these noncovalent interactions are made and their role in protein mediated electron transport is discussed.