Calling the amino acid sequence of a protein/peptide from the nanospectrum produced by a sub-nanometer diameter pore
Abstract The blockade current that develops when a protein translocates across a thin membrane through a sub-nanometer diameter pore informs with extreme sensitivity on the sequence of amino acids that constitute the protein. The current blockade signals measured during the translocation are called...
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Nature Portfolio
2022-10-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-022-22305-x |
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author | Xiaowen Liu Zhuxin Dong Gregory Timp |
author_facet | Xiaowen Liu Zhuxin Dong Gregory Timp |
author_sort | Xiaowen Liu |
collection | DOAJ |
description | Abstract The blockade current that develops when a protein translocates across a thin membrane through a sub-nanometer diameter pore informs with extreme sensitivity on the sequence of amino acids that constitute the protein. The current blockade signals measured during the translocation are called a nanospectrum of the protein. Whereas mass spectrometry (MS) is still the dominant technology for protein identification, it suffers limitations. In proteome-wide studies, MS identifies proteins by database search but often fails to provide high protein sequence coverage. It is also not very sensitive requiring about a femtomole for protein identification. Compared with MS, a sub-nanometer diameter pore (i.e. a sub-nanopore) directly reads the amino acids constituting a single protein molecule, but efficient computational tools are still required for processing and interpreting nanospectra. Here, we delineate computational methods for processing sub-nanopore nanospectra and predicting theoretical nanospectra from protein sequences, which are essential for protein identification. |
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institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-04-12T01:23:13Z |
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spelling | doaj.art-6a5f673504ca47f9a5364feaa30b08282022-12-22T03:53:43ZengNature PortfolioScientific Reports2045-23222022-10-0112111010.1038/s41598-022-22305-xCalling the amino acid sequence of a protein/peptide from the nanospectrum produced by a sub-nanometer diameter poreXiaowen Liu0Zhuxin Dong1Gregory Timp2Tulane Center for Biomedical Informatics and Genomics, Tulane UniversityDepartments of Electrical Engineering and Biological Sciences, University of Notre DameDepartments of Electrical Engineering and Biological Sciences, University of Notre DameAbstract The blockade current that develops when a protein translocates across a thin membrane through a sub-nanometer diameter pore informs with extreme sensitivity on the sequence of amino acids that constitute the protein. The current blockade signals measured during the translocation are called a nanospectrum of the protein. Whereas mass spectrometry (MS) is still the dominant technology for protein identification, it suffers limitations. In proteome-wide studies, MS identifies proteins by database search but often fails to provide high protein sequence coverage. It is also not very sensitive requiring about a femtomole for protein identification. Compared with MS, a sub-nanometer diameter pore (i.e. a sub-nanopore) directly reads the amino acids constituting a single protein molecule, but efficient computational tools are still required for processing and interpreting nanospectra. Here, we delineate computational methods for processing sub-nanopore nanospectra and predicting theoretical nanospectra from protein sequences, which are essential for protein identification.https://doi.org/10.1038/s41598-022-22305-x |
spellingShingle | Xiaowen Liu Zhuxin Dong Gregory Timp Calling the amino acid sequence of a protein/peptide from the nanospectrum produced by a sub-nanometer diameter pore Scientific Reports |
title | Calling the amino acid sequence of a protein/peptide from the nanospectrum produced by a sub-nanometer diameter pore |
title_full | Calling the amino acid sequence of a protein/peptide from the nanospectrum produced by a sub-nanometer diameter pore |
title_fullStr | Calling the amino acid sequence of a protein/peptide from the nanospectrum produced by a sub-nanometer diameter pore |
title_full_unstemmed | Calling the amino acid sequence of a protein/peptide from the nanospectrum produced by a sub-nanometer diameter pore |
title_short | Calling the amino acid sequence of a protein/peptide from the nanospectrum produced by a sub-nanometer diameter pore |
title_sort | calling the amino acid sequence of a protein peptide from the nanospectrum produced by a sub nanometer diameter pore |
url | https://doi.org/10.1038/s41598-022-22305-x |
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