The Manipulation of the Internal Hydrophobicity of FraC Nanopores Augments Peptide Capture and Recognition

Florian Leonardus Rudolfus Lucas, Kumar Sarthak, Erica Mariska Lenting, David Coltan, Nieck Jordy van der Heide, Roderick Corstiaan Abraham Versloot, Aleksei Aksimentiev*, Giovanni Maglia*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Article numberacsnano.0c09958
Pages (from-to)9600-9613
Number of pages14
JournalAcs Nano
Issue number6
Early online date1-Jun-2021
Publication statusPublished - Jul-2021


  • protein sequencing
  • single-molecule
  • mass spectrometry
  • proteomics
  • nanopores
  • nanopore spectrometry

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