期刊
ACS NANO
卷 5, 期 12, 页码 9345-9353出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn203764j
关键词
antibiotics; single-molecule; molecular dynamics; A-site; rRNA; drug discovery
类别
资金
- National Institutes of Health [HG 004767, HG 005115, P41-RR005969, GM 069773]
- National Science Foundation [DMR-095595, PHY-0822613]
- National Institute for Computational Sciences via Teragrid Resources Allocation [MCA05S028]
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [955959] Funding Source: National Science Foundation
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.
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