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Nanopore Sensing of Protein Folding
#MMPMID28693322
Si W
; Aksimentiev A
ACS Nano
2017[Jul]; 11
(7
): 7091-7100
PMID28693322
show ga
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.
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