%0 Journal Article %J ACS Nano %D 2017 %T Nanopore Sensing of Protein Folding %A Si, Wei %A Aleksei Aksimentiev %X

Single-molecule studies of protein folding hold keys to unveiling protein folding pathways and elusive intermediate folding states-attractive pharmaceutical targets. Although conventional single-molecule approaches can detect folding intermediates, they presently lack throughput and require elaborate labeling. Here, we theoretically show that measurements of ionic current through a nanopore containing a protein can report on the protein’s folding state. Our all-atom molecular dynamics (MD) simulations show that the unfolding of a protein lowers the nanopore ionic current, an effect that originates from the reduction of ion mobility in proximity to a protein. Using a theoretical model, we show that the average change in ionic current produced by a folding−unfolding transition is detectable despite the orientational and conformational heterogeneity of the folded and unfolded states. By analyzing millisecond-long all-atom MD simulations of multiple protein transitions, we show that a nanopore ionic current recording can detect folding−unfolding transitions in real time and report on the structure of folding intermediates.

%B ACS Nano %V 11, 7091-7100 %8 05/2017 %G eng %U http://pubs.acs.org/doi/abs/10.1021/acsnano.7b02718 %R 10.1021/acsnano.7b02718