Long-Range Electron Transfer Across Peptide Bridges:  The Transition from Electron Superexchange to Hopping

Malak, Rouba Abdel; Gao, Zhonghua; Wishart, James F.; Isied, Stephan S.

doi:10.1021/ja0401040

Cited by 162 publications

(208 citation statements)

References 22 publications

Supporting

Mentioning

194

Contrasting

Unclassified

Order By: Relevance

“…The λ values reported are in good agreement to experimental values for comparable peptides. 34 The calculated charge transfer parameters in Table 3 contain several noteworthy points. The internal reorganization energy makes up a small but noticeable portion of on average 18% of λ, but reorganization is dominated by the external, mostly solvent, λ s , as would be expected in a system where the charge carrying AAR are exposed to polar solvent.…”

Section: ■ Resultsmentioning

confidence: 99%

Charge Transfer in Model Peptides: Obtaining Marcus Parameters from Molecular Simulation

et al. 2012

View full text Add to dashboard Cite

Charge transfer within and between biomolecules remains a highly active field of biophysics. Due to the complexities of real systems, model compounds are a useful alternative to study the mechanistic fundamentals of charge transfer. In recent years, such model experiments have been underpinned by molecular simulation methods as well. In this work, we study electron hole transfer in helical model peptides by means of molecular dynamics simulations. A theoretical framework to extract Marcus parameters of charge transfer from simulations is presented. We find that the peptides form stable helical structures with sequence dependent small deviations from ideal PPII helices. We identify direct exposure of charged side chains to solvent as a cause of high reorganization energies, significantly larger than typical for electron transfer in proteins. This, together with small direct couplings, makes long-range superexchange electron transport in this system very slow. In good agreement with experiment, direct transfer between the terminal amino acid side chains can be dicounted in favor of a two-step hopping process if appropriate bridging groups exist. ■ INTRODUCTIONCharge transfer is a fundamental phenomenon in physical chemistry, enjoying strong and consistent scientific interest for more than fifty years. 1 Understanding charge transfer in complex and flexible biomolecules is crucial for a huge variety of processes, from cellular respiration and photosynthesis to DNA damage and repair. 2−4 Describing it accurately has turned out to be particularly challenging, both to experimentalists and theoreticians. Biochemical charge transfer involves the directed movement of electrons over large distances (multiple nanometers) through macromolecules, typically proteins or large heterogeneous multiprotein assemblies. These processes involve dynamical changes that occur on a time scale spanning multiple orders of magnitude, from subpicosecond changes in electronic structure to microsecond or even slower conformational changes. Only recently has the complicated interplay between atomic structural fluctuations and electron dynamics become a focus for charge transfer studies in biochemical systems, 5−9 building onto earlier work on model systems. 10−15 This fact, combined with the large system dimensions and difficult experimental conditions, explains why many open questions on electron transfer (ET) in biomolecules remain. Therefore, simpler model systems to study some aspects of ET have gained popularity, and theoretical models based on computer simulations have become important tools to help interpret experiments and gain a better understanding of the structure and function of the involved molecules. 16−22 An important model system in the study of charge transfer processes has always been peptide systems. Extensive experimental work was done by Isied et al., who have studied ET over distances of 8−32 Å via spectroscopical techniques and determined the properties of polyproline II helices as ET bridges. 27−34 This wo...

show abstract

Section: ■ Resultsmentioning

confidence: 99%

Charge Transfer in Model Peptides: Obtaining Marcus Parameters from Molecular Simulation

et al. 2012

View full text Add to dashboard Cite

show abstract

“…36 The distance influence on the ET rate in polyprolines has been until now only assessed for excess electron transfer. 7 Analogous experiments for electron hole transfer are still missing.…”

Section: ■ Methods Of Calculationmentioning

confidence: 99%

Electronic Structure of Hole-Conducting States in Polyprolines

2015

View full text Add to dashboard Cite

Electron transfer over long distances in proteins by a hopping process requires transient relay stations that can harbor charge and spin for a short time span. Certain easily oxidizable or reducible side chains may assume that role, but it has been shown that charge transport in peptides can also take place in the absence of such groups which implies that the peptide backbone provides for hopping stations. We have identified three different types of radical cation states in such peptides that are associated with significantly lower ionization potentials than those of the constituent amino acids, and which may thus serve as relay stations for hole transport. Which of these states is the most stable one depends on the nature and the conformation of the peptide. In contrast to α-helices which, due to their high dipole moments, can only form stable radical cation states that are localized on the C-terminal amino acids, polyprolines are capable of accommodating such states inside the PPII helices and those states may serve as relay stations for hole transfer through polyprolines. Of which type these states are depends often on small conformational changes, and sometimes the most stable states are hybrids of the three types we have identified. ■ INTRODUCTIONThe transport of positive or negative charges over long distances is an essential function in living organisms. 1−3 For distances greater than ca. 2 nm, electron transfer in proteins can only occur in a multistep hopping process via "stepping stones" that are transiently oxidized or reduced during the process. 4,5 These relay stations allow one long and therefore very slow single step electron transfer to be divided into several short but quick steps which make that the rate of the electron transfer via multistep hopping decreases only slightly with the total distance between the electron donor and acceptor. 6,7 Several protein side groups were shown to be able to act as stepping stones in the course of hole transfer in proteins. They can be divided into two groups, the aromatic moieties in tyrosine, tryptophan, and imidazole, and the sulfur containing side chains in cysteine or methionine. The efficiency of the first group to serve as stepping stones is due to their low oxidation or reduction potentials, respectively. 8−10 Methionine on the other hand can only serve as a hole stepping stone if the oxidized sulfur lone pair is stabilized by a nearby aromatic or amide moiety. 11−14 It was also shown that, even in the absence of the above-mentioned side groups, the backbones of α-and 3 10 -helices or β-turns can serve as relay stations. In the case of these structures, a large dipole moment decreases the oxidation potential especially at the C-termini of such structures. 6,15−17 Another secondary structure is the so-called PPII helix which is found in most peptides including electron transport proteins like cytochrome C551 of Pseudomonas aeruginosa or bacteriochlorophyll A in the photosynthetic bacterium Prosthecochloris aestuarii. 18 A major component of...

show abstract

“…[7] However, these mechanisms remain somewhat controversial, with conflicting reports on their application to peptides. [8,9] In an attempt to begin to clarify this we recently reported [10] electron transfer studies on a series of oligomers [H-(NH-C(CH 3 ) 2 -CO) n -NH-CH 2 -Fc, n ¼ 0-5] of a-aminoisobutyric acid (Aib) that contain a C-terminal ferrocene (Fc) for electrochemical studies and a free N-terminus for attachment to a single-walled carbon nanotube array/p-silicon (100) electrode. Oligomers of geminally disubstituted Aib units were used in this study since relatively short sequences (3 or more residues) are known to induce predictable and stable 3 10 -helical structures.…”

Section: Mechanistic Transitionmentioning

confidence: 99%

The Influence of Secondary Structure on Electron Transfer in Peptides

Horsley

2013

Aust. J. Chem.

View full text Add to dashboard Cite

A series of synthetic peptides containing 0-5 a-aminoisobutyric acid (Aib) residues and a C-terminal redox-active ferrocene was synthesised and their conformations defined by NMR and circular dichroism. Each peptide was separately attached to an electrode for subsequent electrochemical analysis in order to investigate the effect of peptide chain length (distance dependence) and secondary structure on the mechanism of intramolecular electron transfer. While the shorter peptides (0-2 residues) do not adopt a well defined secondary structure, the longer peptides (3-5 residues) adopt a helical conformation, with associated intramolecular hydrogen bonding. The electrochemical results on these peptides clearly revealed a transition in the mechanism of intramolecular electron transfer on transitioning from the ill-defined shorter peptides to the longer helical peptides. The helical structures undergo electron transfer via a hopping mechanism, while the shorter ill-defined structures proceeded via an electron superexchange mechanism. Computational studies on two b-peptides PCB-(b 3 Val-b 3 Ala-b 3 Leu) n -NHC(CH 3 ) 2 OOtBu (n ¼ 1 and 2; PCB ¼ p-cyanobenzamide) were consistent with these observations, where the n ¼ 2 peptide adopts a helical conformation and the n ¼ 1 peptide an ill-defined structure. These combined studies suggest that the mechanism of electron transfer is defined by the extent of secondary structure, rather than merely chain length as is commonly accepted.

show abstract

Long-Range Electron Transfer Across Peptide Bridges: The Transition from Electron Superexchange to Hopping

Cited by 162 publications

References 22 publications

Charge Transfer in Model Peptides: Obtaining Marcus Parameters from Molecular Simulation

Charge Transfer in Model Peptides: Obtaining Marcus Parameters from Molecular Simulation

Electronic Structure of Hole-Conducting States in Polyprolines

The Influence of Secondary Structure on Electron Transfer in Peptides

Contact Info

Product

Resources

About