Single-molecule protein identification by sub-nanopore sensors.

Recent advances in top-down mass spectrometry enabled identification of intact proteins, but this technology still faces challenges. For example, top-down mass spectrometry suffers from a lack of sensitivity since the ion counts for a single fragmentation event are often low. In contrast, nanopore t...

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Main Authors: Mikhail Kolmogorov, Eamonn Kennedy, Zhuxin Dong, Gregory Timp, Pavel A Pevzner
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-05-01
Series:PLoS Computational Biology
Online Access:http://europepmc.org/articles/PMC5423552?pdf=render
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author Mikhail Kolmogorov
Eamonn Kennedy
Zhuxin Dong
Gregory Timp
Pavel A Pevzner
author_facet Mikhail Kolmogorov
Eamonn Kennedy
Zhuxin Dong
Gregory Timp
Pavel A Pevzner
author_sort Mikhail Kolmogorov
collection DOAJ
description Recent advances in top-down mass spectrometry enabled identification of intact proteins, but this technology still faces challenges. For example, top-down mass spectrometry suffers from a lack of sensitivity since the ion counts for a single fragmentation event are often low. In contrast, nanopore technology is exquisitely sensitive to single intact molecules, but it has only been successfully applied to DNA sequencing, so far. Here, we explore the potential of sub-nanopores for single-molecule protein identification (SMPI) and describe an algorithm for identification of the electrical current blockade signal (nanospectrum) resulting from the translocation of a denaturated, linearly charged protein through a sub-nanopore. The analysis of identification p-values suggests that the current technology is already sufficient for matching nanospectra against small protein databases, e.g., protein identification in bacterial proteomes.
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spelling doaj.art-c9c3deff1b50448ca7dd887c4a9b00762022-12-22T02:10:27ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582017-05-01135e100535610.1371/journal.pcbi.1005356Single-molecule protein identification by sub-nanopore sensors.Mikhail KolmogorovEamonn KennedyZhuxin DongGregory TimpPavel A PevznerRecent advances in top-down mass spectrometry enabled identification of intact proteins, but this technology still faces challenges. For example, top-down mass spectrometry suffers from a lack of sensitivity since the ion counts for a single fragmentation event are often low. In contrast, nanopore technology is exquisitely sensitive to single intact molecules, but it has only been successfully applied to DNA sequencing, so far. Here, we explore the potential of sub-nanopores for single-molecule protein identification (SMPI) and describe an algorithm for identification of the electrical current blockade signal (nanospectrum) resulting from the translocation of a denaturated, linearly charged protein through a sub-nanopore. The analysis of identification p-values suggests that the current technology is already sufficient for matching nanospectra against small protein databases, e.g., protein identification in bacterial proteomes.http://europepmc.org/articles/PMC5423552?pdf=render
spellingShingle Mikhail Kolmogorov
Eamonn Kennedy
Zhuxin Dong
Gregory Timp
Pavel A Pevzner
Single-molecule protein identification by sub-nanopore sensors.
PLoS Computational Biology
title Single-molecule protein identification by sub-nanopore sensors.
title_full Single-molecule protein identification by sub-nanopore sensors.
title_fullStr Single-molecule protein identification by sub-nanopore sensors.
title_full_unstemmed Single-molecule protein identification by sub-nanopore sensors.
title_short Single-molecule protein identification by sub-nanopore sensors.
title_sort single molecule protein identification by sub nanopore sensors
url http://europepmc.org/articles/PMC5423552?pdf=render
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AT eamonnkennedy singlemoleculeproteinidentificationbysubnanoporesensors
AT zhuxindong singlemoleculeproteinidentificationbysubnanoporesensors
AT gregorytimp singlemoleculeproteinidentificationbysubnanoporesensors
AT pavelapevzner singlemoleculeproteinidentificationbysubnanoporesensors