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The Manipulation of the Internal Hydrophobicity of FraC Nanopores Augments Peptide Capture and Recognition
[Image: see text] The detection of analytes and the sequencing of DNA using biological nanopores have seen major advances over recent years. The analysis of proteins and peptides with nanopores, however, is complicated by the complex physicochemical structure of polypeptides and the lack of understa...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American
Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223486/ https://www.ncbi.nlm.nih.gov/pubmed/34060809 http://dx.doi.org/10.1021/acsnano.0c09958 |
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author | Lucas, Florian Leonardus Rudolfus Sarthak, Kumar Lenting, Erica Mariska Coltan, David van der Heide, Nieck Jordy Versloot, Roderick Corstiaan Abraham Aksimentiev, Aleksei Maglia, Giovanni |
author_facet | Lucas, Florian Leonardus Rudolfus Sarthak, Kumar Lenting, Erica Mariska Coltan, David van der Heide, Nieck Jordy Versloot, Roderick Corstiaan Abraham Aksimentiev, Aleksei Maglia, Giovanni |
author_sort | Lucas, Florian Leonardus Rudolfus |
collection | PubMed |
description | [Image: see text] The detection of analytes and the sequencing of DNA using biological nanopores have seen major advances over recent years. The analysis of proteins and peptides with nanopores, however, is complicated by the complex physicochemical structure of polypeptides and the lack of understanding of the mechanism of capture and recognition of polypeptides by nanopores. In this work, we show that introducing aromatic amino acids at precise positions within the lumen of α-helical fragaceatoxin C (FraC) nanopores increased the capture frequency of peptides and largely improved the discrimination among peptides of similar size. Molecular dynamics simulations determined the sensing region of the nanopore, elucidated the microscopic mechanism enabling accurate characterization of the peptides via ionic current blockades in FraC, and characterized the effect of the pore modification on peptide discrimination. This work provides insights to improve the recognition and to augment the capture of peptides by nanopores, which is important for developing a real-time and single-molecule size analyzer for peptide recognition and identification. |
format | Online Article Text |
id | pubmed-8223486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-82234862021-06-25 The Manipulation of the Internal Hydrophobicity of FraC Nanopores Augments Peptide Capture and Recognition Lucas, Florian Leonardus Rudolfus Sarthak, Kumar Lenting, Erica Mariska Coltan, David van der Heide, Nieck Jordy Versloot, Roderick Corstiaan Abraham Aksimentiev, Aleksei Maglia, Giovanni ACS Nano [Image: see text] The detection of analytes and the sequencing of DNA using biological nanopores have seen major advances over recent years. The analysis of proteins and peptides with nanopores, however, is complicated by the complex physicochemical structure of polypeptides and the lack of understanding of the mechanism of capture and recognition of polypeptides by nanopores. In this work, we show that introducing aromatic amino acids at precise positions within the lumen of α-helical fragaceatoxin C (FraC) nanopores increased the capture frequency of peptides and largely improved the discrimination among peptides of similar size. Molecular dynamics simulations determined the sensing region of the nanopore, elucidated the microscopic mechanism enabling accurate characterization of the peptides via ionic current blockades in FraC, and characterized the effect of the pore modification on peptide discrimination. This work provides insights to improve the recognition and to augment the capture of peptides by nanopores, which is important for developing a real-time and single-molecule size analyzer for peptide recognition and identification. American Chemical Society 2021-06-01 2021-06-22 /pmc/articles/PMC8223486/ /pubmed/34060809 http://dx.doi.org/10.1021/acsnano.0c09958 Text en © 2021 The Authors. Published by American Chemical Society Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Lucas, Florian Leonardus Rudolfus Sarthak, Kumar Lenting, Erica Mariska Coltan, David van der Heide, Nieck Jordy Versloot, Roderick Corstiaan Abraham Aksimentiev, Aleksei Maglia, Giovanni The Manipulation of the Internal Hydrophobicity of FraC Nanopores Augments Peptide Capture and Recognition |
title | The
Manipulation of the Internal Hydrophobicity of
FraC Nanopores Augments Peptide Capture and Recognition |
title_full | The
Manipulation of the Internal Hydrophobicity of
FraC Nanopores Augments Peptide Capture and Recognition |
title_fullStr | The
Manipulation of the Internal Hydrophobicity of
FraC Nanopores Augments Peptide Capture and Recognition |
title_full_unstemmed | The
Manipulation of the Internal Hydrophobicity of
FraC Nanopores Augments Peptide Capture and Recognition |
title_short | The
Manipulation of the Internal Hydrophobicity of
FraC Nanopores Augments Peptide Capture and Recognition |
title_sort | the
manipulation of the internal hydrophobicity of
frac nanopores augments peptide capture and recognition |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223486/ https://www.ncbi.nlm.nih.gov/pubmed/34060809 http://dx.doi.org/10.1021/acsnano.0c09958 |
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