The applications of nanopores in studies of proteins

Ding, Ting; Chen, Antony K.; Zhang, Lu

doi:10.1016/j.scib.2019.07.029

Cited by 7 publications

(5 citation statements)

References 120 publications

(126 reference statements)

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“…These systems paved the way to the extraordinary evolution of nanaopore-based technologies as a label-free, amplification-free, single-molecule investigative approach, that greatly advanced fields such as DNA sequencing (Figure 2), single-molecule protein studies (Figure 3), sensing and medical diagnostic [47,48,68,[81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99].…”

Section: Significance Statementmentioning

confidence: 99%

Single‐molecule, hybridization‐based strategies for short nucleic acids detection and recognition with nanopores

et al. 2021

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DNA nanotechnology has seen large developments over the last 30 years through the combination of detection and discovery of DNAs, and solid phase synthesis to increase the chemical functionalities on nucleic acids, leading to the emergence of novel and sophisticated in features, nucleic acids-based biopolymers. Arguably, nanopores developed for fast and direct detection of a large variety of molecules, are part of a revolutionary technological evolution which led to cheaper, smaller and considerably easier to use devices enabling DNA detection and sequencing at the single-molecule level. Through their versatility, the nanopore-based tools proved useful biomedicine, nanoscale chemistry, biology and physics, as well as other disciplines spanning materials science to ecology and anthropology. This mini-review discusses the progress of nanopore-and hybridization-based DNA detection, and explores a range of state-ofthe-art applications afforded through the combination of certain synthetically-derived polymers mimicking nucleic acids and nanopores, for the single-molecule biophysics on short DNA structures.

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Section: Significance Statementmentioning

confidence: 99%

Single‐molecule, hybridization‐based strategies for short nucleic acids detection and recognition with nanopores

et al. 2021

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“…With unique 3D structures, low charge density, and diverse charge distribution of amino acids, protein detection is more challenging as compared with that of DNA (Hu Z. L. et al, 2021). Most of the traditional techniques require a large number of identical protein samples, wherein it is challenging to record a singleprotein conformational change in a real-time manner (Ding et al, 2019). The nanopore-based approaches can achieve sensitive and label-free detection of a single protein even at extremely low concentrations as well as provide a dynamic view of protein conformation, confirming their ability for protein characterization (Acharya et al, 2020).…”

Section: Protein Detection and Sequencingmentioning

confidence: 99%

Single-Entity Detection With TEM-Fabricated Nanopores

Saqib

Hao

2021

Front. Chem.

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Nanopore-based single-entity detection shows immense potential in sensing and sequencing technologies. Solid-state nanopores permit unprecedented detail while preserving mechanical robustness, reusability, adjustable pore size, and stability in different physical and chemical environments. The transmission electron microscope (TEM) has evolved into a powerful tool for fabricating and characterizing nanometer-sized pores within a solid-state ultrathin membrane. By detecting differences in the ionic current signals due to single-entity translocation through the nanopore, solid-state nanopores can enable gene sequencing and single molecule/nanoparticle detection with high sensitivity, improved acquisition speed, and low cost. Here we briefly discuss the recent progress in the modification and characterization of TEM-fabricated nanopores. Moreover, we highlight some key applications of these nanopores in nucleic acids, protein, and nanoparticle detection. Additionally, we discuss the future of computer simulations in DNA and protein sequencing strategies. We also attempt to identify the challenges and discuss the future development of nanopore-detection technology aiming to promote the next-generation sequencing technology.

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“…Nanopore technology provides exciting opportunities for characterizing proteins, it probes them at a single molecule level, typically requires very small amount of sample (∼ nM), and is a label free method 1,2 . This technology has been used in many applications, such as in protein sensing 2,3 , monitoring conformational changes of proteins such as folding/unfolding [4][5][6][7][8] , and for self-assembly of proteins inside a nanopore [9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

“…This technology has been used in many applications, such as in protein sensing 2,3 , monitoring conformational changes of proteins such as folding/unfolding [4][5][6][7][8] , and for self-assembly of proteins inside a nanopore [9][10][11] . Recently, there has been a lot of development and numerous opportunities in nanopore analysis of proteins, as evident from the large number of review articles in this particular field in just the past few years [1][2][3][12][13][14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

“…This technology has been used in many applications, such as in protein sensing 2,3 , monitoring conformational changes of proteins such as folding/unfolding 4–8 , and for self-assembly of proteins inside a nanopore 9–11 . Recently, there has been a lot of development and numerous opportunities in nanopore analysis of proteins, as evident from the large number of review articles in this particular field in just the past few years 1–3,12–16 . Protein analysis using nanopores is an indirect method wherein the structural and/or dynamic properties of a protein molecule are interpreted through ionic current trace.…”

Section: Introductionmentioning

confidence: 99%

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Langevin dynamics simulation of protein dynamics in nanopores at microsecond timescales

Muthukumar

Mahalik

Cifello

2021

Preprint

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With rapid advancement in the fields of nanopore analysis of protein, it has become imperative to develop modeling framework for understanding the protein dynamics in nanopores. Such modeling framework should include the effects of electro-osmosis, as it plays significant role during protein translocation in confinement. Currently, the molecular dynamics simulations that include the hydrodynamic effects are limited to a timescale of few 100 ns. These simulations give insight about important events like protein unfolding which occurs in this timescale. But many electrophoresis experiments are limited by a detector resolution of approximately 2.5 microseconds. Analytical theory has been used to interpret protein dynamics at such large timescale. There is a need for molecular modeling of more complex environment and protein shapes which cannot be accounted for by analytical theory. We have developed a framework to study globular protein dynamics in nanopores by using langevin dynamics on a rigid body model of protein and the hydrodynamics is accounted by analytical theory for simple cylindrical nanopore geometry. This framework has been applied to study the dynamics of Ubiquitin translocation in SiNx nanopore by Nir et al. They have reported 7 times decrease in average dwell time of the protein inside the nanopore in response to a small change in pH from 7.0 to 7.2 and the modification of protein charge was attributed for such drastic change. Closer examination using our simulation revealed that the electro-osmotic effects originating due to very small change in the surface electrostatic potential of the nanopore could lead to such a drastic change in protein dynamics.

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The applications of nanopores in studies of proteins

Cited by 7 publications

References 120 publications

Single‐molecule, hybridization‐based strategies for short nucleic acids detection and recognition with nanopores

Single‐molecule, hybridization‐based strategies for short nucleic acids detection and recognition with nanopores

Single-Entity Detection With TEM-Fabricated Nanopores

Langevin dynamics simulation of protein dynamics in nanopores at microsecond timescales

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