Molecular Determinants of Current Blockade Produced by Peptide Transport Through a Nanopore

Jingqian Liu, Aleksei Aksimentiev

Research output: Contribution to journalReview articlepeer-review

Abstract

The nanopore sensing method holds the promise of delivering a single molecule technology for identification of biological proteins, direct detection of post-translational modifications, and perhaps de novo determination of a protein’s amino acid sequence. The key quantity measured in such nanopore sensing experiments is the magnitude of the ionic current passing through a nanopore blocked by a polypeptide chain. Establishing a relationship between the amino acid sequence of a peptide fragment confined within a nanopore and the blockade current flowing through the nanopore remains a major challenge for realizing the nanopore protein sequencing. Using the results of all-atom molecular dynamics simulations, here we compare nanopore sequencing of DNA with nanopore sequencing of proteins. We then delineate the factors affecting the blockade current modulation by the peptide sequence, showing that the current can be determined by (i) the steric footprint of an amino acid, (ii) its interactions with the pore wall, (iii) the local stretching of a polypeptide chain, and (iv) the local enhancement of the ion concentration at the nanopore constriction. We conclude with a brief discussion of the prospects for purely computational prediction of the blockade currents.

Original languageEnglish (US)
Pages (from-to)21-29
Number of pages9
JournalACS Nanoscience Au
Volume4
Issue number1
DOIs
StatePublished - Feb 21 2024

Keywords

  • current blockade
  • ionic current
  • molecular dynamics
  • nanopores
  • post-translational modifications
  • protein sequencing
  • translocation

ASJC Scopus subject areas

  • Chemistry (miscellaneous)
  • Materials Science (miscellaneous)

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