Work

Nanopore Sensing of Protein Folding

Year: 2017

Type: article

Abstract: 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.

Source: ACS Nano

DOI: 10.1021/acsnano.7b02718

Authors: Wei Si, Aleksei Aksimentiev

Institutions: University of Illinois Urbana-Champaign, Southeast University

Language: English

Topic: Nanopore and Nanochannel Transport Studies

Subfield: Biomedical Engineering

Field: Engineering

Domain: Physical Sciences

Open Access status: green

Funders: National Natural Science Foundation of China, China Scholarship Council, National Human Genome Research Institute

Awards: Plasmonic nanopores for trapping, controlled motion and sequencing of DNA, G5006096157, G5418950717