Stretching and unzipping nucleic acid hairpins using a synthetic nanopore

Zhao, Qian; Comer, Jeffrey; Dimitrov, V.; Yemenicioglu, Sukru; Aksimentiev, Aleksei; Timp, G.

doi:10.1093/nar/gkm1017

Cited by 66 publications

(95 citation statements)

References 40 publications

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“…As tabulated in Fig. 3a, the symbol "+" denotes the event that DNA could pass through nanopores retaining its double-stranded structure; the symbol "À" denotes the event that DNA could not pass through nanopores or that the doublestranded structure of DNA was disintegrated (such as by unwinding or unzipping [48][49][50] ) during the translocation. As shown in Fig.…”

Section: Impact Of Number Of Graphene Layers On Dna Translocation Thrmentioning

confidence: 99%

The impact of the number of layers of a graphene nanopore on DNA translocation

Chen

2013

Soft Matter

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Graphene nanopore based sensor devices have shown great potential for the detection of DNA. To understand the fundamental aspects of DNA translocation through a graphene nanopore, in this work, molecular dynamics (MD) simulations and potential of mean force (PMF) calculations were carried out to investigate the impact of the number of graphene layers of small nanopores (2-3 nm) on DNA translocation. It was observed that the ionic conductance was sensitive to the number of graphene layers of open-nanopores, and the probability of DNA translocation through graphene nanopores was related to the thickness of the graphene nanopores. MD simulations showed that DNA translocation time was most sensitive to the thickness of graphene nanopores of 2.4 nm aperture, and the observed free energy barrier of PMFs and the profile change revealed the increased retardation of DNA translocation through bilayer graphene nanopores as compared to that through monolayer graphene nanopores.

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Section: Impact Of Number Of Graphene Layers On Dna Translocation Thrmentioning

confidence: 99%

The impact of the number of layers of a graphene nanopore on DNA translocation

Chen

2013

Soft Matter

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“…For pore diameters below 1.5 nm, the hairpin unzips breaking the hydrogen bonds making up the basepairs in the duplex. However, if the nanopore is between 1.6 and 2.3 nm, respectively, the dsDNA head of the hairpin will actually stretch, transitioning from B-form to the S-form or stretched form of DNA due to the strong electric field present in the pore [52], [74]. S-form DNA is around 1.7 times longer and 30% smaller in diameter compared to B-form DNA [75].…”

Section: Progress Towards Sequencingmentioning

confidence: 99%

“…S-form DNA is around 1.7 times longer and 30% smaller in diameter compared to B-form DNA [75]. Unzipping actually requires less energy than stretching the duplex, and correspondingly will occur at a lower electric field strength [74]. …”

Section: Progress Towards Sequencingmentioning

confidence: 99%

Nanopore Sequencing: Electrical Measurements of the Code of Life

Timp

Mirsaidov

Wang

et al. 2010

IEEE Trans. Nanotechnology

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Sequencing a single molecule of deoxyribonucleic acid (DNA) using a nanopore is a revolutionary concept because it combines the potential for long read lengths (>5 kbp) with high speed (1 bp/10 ns), while obviating the need for costly amplification procedures due to the exquisite single molecule sensitivity. The prospects for implementing this concept seem bright. The cost savings from the removal of required reagents, coupled with the speed of nanopore sequencing places the $1000 genome within grasp. However, challenges remain: high fidelity reads demand stringent control over both the molecular configuration in the pore and the translocation kinetics. The molecular configuration determines how the ions passing through the pore come into contact with the nucleotides, while the translocation kinetics affect the time interval in which the same nucleotides are held in the constriction as the data is acquired. Proteins like α-hemolysin and its mutants offer exquisitely precise self-assembled nanopores and have demonstrated the facility for discriminating individual nucleotides, but it is currently difficult to design protein structure ab initio, which frustrates tailoring a pore for sequencing genomic DNA. Nanopores in solid-state membranes have been proposed as an alternative because of the flexibility in fabrication and ease of integration into a sequencing platform. Preliminary results have shown that with careful control of the dimensions of the pore and the shape of the electric field, control of DNA translocation through the pore is possible. Furthermore, discrimination between different base pairs of DNA may be feasible. Thus, a nanopore promises inexpensive, reliable, high-throughput sequencing, which could thrust genomic science into personal medicine.

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“…The two strands comprising the double helix do not pass through pores with diameters 1.6 < d < 2.5 nm in the same way as they do through larger pores. 45,46 The confinement of the smaller pores causes the base-pair to tilt. Due to the activation energy required to begin this stretching transition, no DNA will be able to translocate below the threshold.…”

Section: Stretching Genes Using a Nanoporementioning

confidence: 99%

Molecular diagnostics for personal medicine using a nanopore

Mirsaidov

Wang

Timp

et al. 2010

WIREs Nanomed Nanobiotechnol

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Semiconductor nanotechnology has created the ultimate analytical tool: a nanopore with single molecule sensitivity. This tool offers the intriguing possibility of high- throughput, low cost sequencing of DNA with the absolute minimum of material and preprocessing. The exquisite single molecule sensitivity obviates the need for costly and error-prone procedures like polymerase chain reaction amplification. Instead, nanopore sequencing relies on the electric signal that develops when a DNA molecule translocates through a pore in a membrane. If each base pair has a characteristic electrical signature, then ostensibly a pore could be used to analyze the sequence by reporting all of the signatures in a single read without resorting to multiple DNA copies. The potential for a long read length combined with high translocation velocity should make resequencing inexpensive and allow for haplotyping and methylation profiling in a chromosome.

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Stretching and unzipping nucleic acid hairpins using a synthetic nanopore

Cited by 66 publications

References 40 publications

The impact of the number of layers of a graphene nanopore on DNA translocation

The impact of the number of layers of a graphene nanopore on DNA translocation

Nanopore Sequencing: Electrical Measurements of the Code of Life

Molecular diagnostics for personal medicine using a nanopore

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