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*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

2 Citaten (Scopus)
7 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Artikelnummeracsnano.0c09958
Pagina's (van-tot)9600-9613
Aantal pagina's14
TijdschriftAcs Nano
Volume15
Nummer van het tijdschrift6
Vroegere onlinedatum1-jun-2021
DOI's
StatusPublished - jul-2021

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