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...
Main Authors: | , , , , |
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2017-05-01
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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. |
first_indexed | 2024-04-14T05:13:57Z |
format | Article |
id | doaj.art-c9c3deff1b50448ca7dd887c4a9b0076 |
institution | Directory Open Access Journal |
issn | 1553-734X 1553-7358 |
language | English |
last_indexed | 2024-04-14T05:13:57Z |
publishDate | 2017-05-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS Computational Biology |
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 |
work_keys_str_mv | AT mikhailkolmogorov singlemoleculeproteinidentificationbysubnanoporesensors AT eamonnkennedy singlemoleculeproteinidentificationbysubnanoporesensors AT zhuxindong singlemoleculeproteinidentificationbysubnanoporesensors AT gregorytimp singlemoleculeproteinidentificationbysubnanoporesensors AT pavelapevzner singlemoleculeproteinidentificationbysubnanoporesensors |