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

Research output: Contribution to journalArticlepeer-review

Abstract

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 (US)
Pages (from-to)9600-9613
Number of pages14
JournalACS Nano
Volume15
Issue number6
DOIs
StatePublished - Jun 22 2021

Keywords

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

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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