Probing electrical conductivity of proteins through microscopic simulations

Until recently, proteins have been largely regarded as good electrical insulators. Recent single protein conductance experiments from the Lindsay lab at ASU show that proteins can conduct electrical current surprisingly well provided they are connected to the electrodes via ligand recognition interactions. Despite the significant experimental evidence of this phenomenon for multiple protein species, there is very little theoretical and mechanistic understanding of the underlying electron transport leading to the high conductance. Here, we probe a possible mechanism for the charge transport where electron hopping between active residues in the protein is driven by the nuclear polarization fluctuations, as described in the Marcus theory. The statistics of nuclear fluctuations, however, violate the fluctuation dissipation relation between the first and second moments of the reaction coordinate thus leading to activation barriers for the hops substantially lower than prescribed by the traditional Marcus formulation. We apply this nonergodic theory of charge transport, incorporating the fluctuation-dissipation violation, to the analysis of all-atom molecular dynamics simulations of a CTPR8 protein to calculate the individual hopping rates between the active residues. The hopping rates are used as input to a kinetic Monte Carlo simulation to calculate the overall electron current through the protein. The currents obtained thereby are in the nanoampere ranges, in agreement with the results of single protein conductance measurements. We envision future applications of our computational method to study change transport in single protein detection devices, contributing to the development of new protein sequencing methods and direct electronic detection of disease biomarkers