Nanopore analysis of individual RNA/antibiotic complexes

Meni Wanunu, Swati Bhattacharya, Yun Xie, Yitzhak Tor, Aleksei Aksimentiev, Marija Drndic

Research output: Contribution to journalArticlepeer-review

Abstract

Nanopores in thin solid-state membranes are used to rapidly analyze individual RNA/drug complexes. The interactions of a truncated A-site RNA model of the prokaryotic ribosome with aminoglycoside antibiotics are characterized by passing individual molecules through a 3-3.5 nm diameter pore fabricated in a 8-10 nm thick silicon nitride membrane. Complexes of the A-site RNA with aminoglycosides can be distinguished from unbound A-site based on the ion current signatures produced as they pass through the nanopores. Counting the fraction of free and drug-bound molecules affords label-free drug-RNA binding isotherms consistent with literature reports and with data generated using independent fluorescence-based assays. Our measurements are supported by molecular dynamics simulations, which illustrate the relationship between the ionic current and complexation of the A-site RNA with paramomycin, a prototypical aminoglycoside antibiotic.

Original languageEnglish (US)
Pages (from-to)9345-9353
Number of pages9
JournalACS Nano
Volume5
Issue number12
DOIs
StatePublished - Dec 27 2011

Keywords

  • A-site
  • antibiotics
  • drug discovery
  • molecular dynamics
  • rRNA
  • single-molecule

ASJC Scopus subject areas

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

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