Long-Range Conductivity in Proteins Mediated by Aromatic Residues

Abstract

Single-molecule measurements show that many proteins, lacking any redox cofactors, nonetheless exhibit electrical conductance on the order of a nanosiemen over 10 nm distances, implying that electrons can transit an entire protein in less than a nanosecond when subject to a potential difference of less than 1 V. This is puzzling because, for fast transport (i.e., a free energy barrier of zero), the hopping rate is determined by the reorganization energy of approximately 0.8 eV, and this sets the time scale of a single hop to at least 1 μs. Furthermore, the Fermi energies of typical metal electrodes are far removed from the energies required for sequential oxidation and reduction of the aromatic residues of the protein, which should further reduce the hopping current. Here, we combine all-atom molecular dynamics (MD) simulations of non-redox-active proteins (consensus tetratricopeptide repeats) with an electron transfer theory to demonstrate a molecular mechanism that can account for the unexpectedly fast electron transport. According to our MD simulations, the reorganization energy produced by the energy shift on charging (the Stokes shift) is close to the conventional value of 0.8 eV. However, the non-ergodic sampling of molecular configurations by the protein results in reaction-reorganization energies, extracted directly from the distribution of the electrostatic energy fluctuations, that are only ∼0.2 eV, which is small enough to enable long-range conductivity, without invoking quantum coherent transport. Using the MD values of the reorganization energies, we calculate a current decay with distance that is in agreement with experiment.

Tryptophan to Tryptophan Hole Hopping in an Azurin Construct

“…Coupling with environmental fluctuations reduces the outer sphere reorganization energy λ o and the driving force but by different amounts. 33,39,40,46 It accounts well for experimentally determined ultrafast rates and predicts stretched-exponential kinetics. 39 In accord with prediction, the first hopping step in all Trp-containing Re-azurins investigated so far displays multiexponential kinetics.…”

Heavy Water Reduces the Electronic Conductance of Protein Wires via Deuteron Interactions with Aromatic Residues

“…The mechanism of charge transfer is debated (quantum tunneling vs hopping conductance) . In the case of the linear series of proteins that are the subject of this report, an all-atom calculation of hopping rates gave results in good agreement with experiment . To clarify the connection between these calculations and a simple model of conductivity, we use the result for a conducting rod for which the resistance of these proteins as a function of length is given by R ( L ) = R 0 + ρ L A = R 0 + 1 n e μ L A = R 0 + 1 n D k T e 2 L A where R 0 is the contact resistance and ρ/ A is the ratio of resistivity to the effective cross sectional area of the molecule.…”

“…The phenylalanine residues cannot form stable radical cations, preventing hopping conductivity involving fully oxidized residues (though insertion of phenylalanine residues into bacterial filaments enhances conductivity) . The Phe-zipper is nearly as conductive as the Trp-Zipper, an effect that might be explained by the finding that the “oxidized” states involved in this rapid transport are only partly relaxed . The original zipper (Table S1) was 75% as conductive as the second version with a 3aa deletion.…”

“…The additional length alone cannot account for this change because of the slow decay of the current with distance. The difference presumably reflects differences in the barrier to charge injection at the ends of the molecule (where tunneling transport dominates, leading to a strong distance dependence in the contact region) …”

Efficient Electron Hopping Transport through Azurin-Based Junctions

“…The field of protein electronics has flourished remarkably over the past decade . The interest in these systems is mainly triggered by the highly efficient charge-transfer that proteins can exhibit over long distances, , besides their role in extremely important processes such as in the respiratory and photosynthetic chains. , However, experimental advances have also enabled the study of electron transport through proteins incorporated in solid-state junctions. , This has paved the way for the development of future electrical devices based on proteins as active elements, as well as their use in sensors and biocompatible devices . In addition, interesting mechanical, self-assembly, chemical recognition, and optoelectronic properties have been revealed which could be exploited in the development of such new-generation devices.…”