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...

Full description

Bibliographic Details
Main Authors: Xiaowen Liu, Zhuxin Dong, Gregory Timp
Format: Article
Language:English
Published: Nature Portfolio 2022-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-22305-x
_version_ 1828164287305089024
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.
first_indexed 2024-04-12T01:23:13Z
format Article
id doaj.art-6a5f673504ca47f9a5364feaa30b0828
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-04-12T01:23:13Z
publishDate 2022-10-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
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
work_keys_str_mv AT xiaowenliu callingtheaminoacidsequenceofaproteinpeptidefromthenanospectrumproducedbyasubnanometerdiameterpore
AT zhuxindong callingtheaminoacidsequenceofaproteinpeptidefromthenanospectrumproducedbyasubnanometerdiameterpore
AT gregorytimp callingtheaminoacidsequenceofaproteinpeptidefromthenanospectrumproducedbyasubnanometerdiameterpore