Skip to main content
SpringerLink
Log in

DNA sequencing technology based on nanopore sensors by theoretical calculations and simulations

  • Review
  • Analytical Chemistry
  • Published:
Chinese Science Bulletin

Abstract

DNA sequencing based on nanopore sensors is a promising tool for third-generation sequencing technology because of its special properties, such as revolutionized speed and low cost. With about two decades of nanopore technology development, the pioneering work has demonstrated the ability of nanopores to perform single-molecule detection and DNA sequencing. However, the microscopic mechanisms of DNA transport dynamics through nanopores remain largely unknown. Currently, DNA microscopic transport in a nanopore is difficult to characterize and several unexpected experimental observations are equivocal. This limitation can be resolved using theoretical calculations and simulations. These computational methods can monitor the entire dynamic process that DNA undergoes in solution at a single-atom resolution that can accurately unveil the mystery of DNA transport dynamics and predict certain unexpected phenomena. This paper mainly reports the recent applications of computational and simulation methods applied to the study of DNA transport through both biological and synthetic nanopores. We hope the theoretical calculations and simulations of DNA transport through nanopores can benefit the design of DNA sequencing devices.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Mereuta L, Roy M, Asandei A et al (2014) Slowing down single-molecule trafficking through a protein nanopore reveals intermediates for peptide translocation. Sci Rep 4:3885

    Article  Google Scholar 

  2. Ying YL, Zhang JJ, Meng FN et al (2013) A stimuli-responsive nanopore based on a photoresponsive host-guest system. Sci Rep 3:1662

    Article  Google Scholar 

  3. Liu K, Feng J, Kis A et al (2014) Atomically thin molybdenum disulfide nanopores with high sensitivity for DNA translocation. ACS Nano 8:2504–2511

    Article  Google Scholar 

  4. Zhou Z, Hu Y, Wang H et al (2013) DNA translocation through hydrophilic nanopore in hexagonal boron nitride. Sci Rep 3:3287

    Google Scholar 

  5. Chen YS, Lee CH, Hung MY et al (2013) DNA sequencing using electrical conductance measurements of a DNA polymerase. Nat Nantechnol 8:452–458

    Article  Google Scholar 

  6. Schneider GF, Xu Q, Hage S et al (2013) Tailoring the hydrophobicity of graphene for its use as nanopores for DNA translocation. Nat Commun 4:2619

    Google Scholar 

  7. Liu S, Lu B, Zhao Q et al (2013) Boron nitride nanopores: highly sensitive DNA single-molecule detectors. Adv Mater 25:4549–4554

    Article  Google Scholar 

  8. Li W, Bell NAW, Hernandez-Ainsa S et al (2013) Single protein molecule detection by glass nanopores. ACS Nano 7:4129–4134

    Article  Google Scholar 

  9. Kasianowicz JJ, Brandin E, Branton D et al (1996) Characterization of individual polynucleotide molecules using a membrane channel. Proc Natl Acad Sci USA 93:13770–13773

    Article  Google Scholar 

  10. Venta K, Shemer G, Puster M et al (2013) Differentiation of short, single-stranded DNA homopolymers in solid-state nanopores. ACS Nano 7:4629–4636

    Article  Google Scholar 

  11. Wen S, Zeng T, Liu L et al (2011) Highly sensitive and selective DNA-based detection of mercury(ii) with alpha-hemolysin nanopore. J Am Chem Soc 133:18312–18317

    Article  Google Scholar 

  12. Yang C, Liu L, Zeng T et al (2013) Highly sensitive simultaneous detection of lead(ii) and barium(ii) with g-quadruplex DNA in α-hemolysin nanopore. Anal Chem 85:7302–7307

    Article  Google Scholar 

  13. Keyser UF, Koeleman BN, Van Dorp S et al (2006) Direct force measurements on DNA in a solid-state nanopore. Nat Phys 2:473–477

    Article  Google Scholar 

  14. Clarke J, Wu HC, Jayasinghe L et al (2009) Continuous base identification for single-molecule nanopore DNA sequencing. Nat Nanotechnol 4:265–270

    Article  Google Scholar 

  15. Akeson M, Branton D, Kasianowicz JJ et al (1999) Microsecond time-scale discrimination among polycytidylic acid, polyadenylic acid, and polyuridylic acid as homopolymers or as segments within single rna molecules. Biophys J 77:3227–3233

    Article  Google Scholar 

  16. Zwolak M, Di Ventra M (2008) Colloquium: physical approaches to DNA sequencing and detection. Rev Mod Phys 80:141–165

    Article  Google Scholar 

  17. Purnell RF, Mehta KK, Schmidt JJ (2008) Nucleotide identification and orientation discrimination of DNA homopolymers immobilized in a protein nanopore. Nano Lett 8:3029–3034

    Article  Google Scholar 

  18. Stoddart D, Heron AJ, Mikhailova E et al (2009) Single-nucleotide discrimination in immobilized DNA oligonucleotides with a biological nanopore. Proc Natl Acad Sci USA 106:7702–7707

    Article  Google Scholar 

  19. Aksimentiev A, Schulten K (2005) Imaging alpha-hemolysin with molecular dynamics: ionic conductance, osmotic permeability, and the electrostatic potential map. Biophys J 88:3745–3761

    Article  Google Scholar 

  20. Bhattacharya S, Derrington IM, Pavlenok M et al (2012) Molecular dynamics study of mspa arginine mutants predicts slow DNA translocations and ion current blockades indicative of DNA sequence. ACS Nano 6:6960–6968

    Article  Google Scholar 

  21. Qiu H, Guo WL (2012) Detecting ssdna at single-nucleotide resolution by sub-2-nanometer pore in monoatomic graphene: A molecular dynamics study. Appl Phys Lett 100:083106

    Article  Google Scholar 

  22. Aksimentiev A (2010) Deciphering ionic current signatures of DNA transport through a nanopore. Nanoscale 2:468–483

    Article  Google Scholar 

  23. Venkatesan BM, Bashir R (2011) Nanopore sensors for nucleic acid analysis. Nat Nanotechnol 6:615–624

    Article  Google Scholar 

  24. Branton D, Deamer DW, Marziali A et al (2008) The potential and challenges of nanopore sequencing. Nat Biotechnol 26:1146–1153

    Article  Google Scholar 

  25. Min SK, Kim WY, Cho Y et al (2011) Fast DNA sequencing with a graphene-based nanochannel device. Nat Nanotechnol 6:162–165

    Article  Google Scholar 

  26. Li J, Zhang Y, Yang J et al (2013) Molecular dynamics study of DNA translocation through graphene nanopores. Phys Rev E 87:062707

    Article  Google Scholar 

  27. Lansac Y, Maiti PK, Glaser MA (2004) Coarse-grained simulation of polymer translocation through an artificial nanopore. Polymer 45:3099–3110

    Article  Google Scholar 

  28. Tian P, Smith GD (2003) Translocation of a polymer chain across a nanopore: a brownian dynamics simulation study. J Chem Phys 119:11475–11483

    Article  Google Scholar 

  29. Chen CM (2005) Driven translocation dynamics of polynucleotides through a nanopore: off-lattice monte-carlo simulations. Phys A 350:95–107

    Article  Google Scholar 

  30. Lebrun A, Lavery R (1996) Modelling extreme stretching of DNA. Nucleic Acids Res 24:2260–2267

    Article  Google Scholar 

  31. Maffeo C, Schopflin R, Brutzer H et al (2010) DNA-DNA interactions in tight supercoils are described by a small effective charge density. Phys Rev Lett 105:158101

    Article  Google Scholar 

  32. Luan B, Aksimentiev A (2008) DNA attraction in monovalent and divalent electrolytes. J Am Chem Soc 130:15754–15755

    Article  Google Scholar 

  33. Kong Y, Cui DX, Ozkan CS et al (2003) Modelling carbon nanotube based bio-nano systems: a molecular dynamics study. In: Ozkan CS, Santini JT, Gao H et al (eds) Symposium on biomicroelectromechanical systems (BioMEMS) held at the 2003 MRS Spring Meeting, San Francisco, April 2003. Materials research society symposium proceedings, vol 773. Materials Research Society, WARRENDALE, pp 111–116

  34. Li Z, Yang W (2010) Capture and manipulation of hybrid dnas by carbon nanotube bundles. Nanotechnology 21:195301

    Article  Google Scholar 

  35. Enyashin AN, Gemming S, Seifert G (2007) DNA-wrapped carbon nanotubes. Nanotechnology 18:245702

    Article  Google Scholar 

  36. Liu YL, Iqbal SM (2009) A mesoscale model of DNA interaction with functionalized nanopore. Appl Phys Lett 95:223701

    Article  Google Scholar 

  37. Wanunu M, Morrison W, Rabin Y et al (2010) Electrostatic focusing of unlabelled DNA into nanoscale pores using a salt gradient. Nat Nanotechnol 5:160–165

    Article  Google Scholar 

  38. Hatlo MM, Panja D, van Roij R (2011) Translocation of DNA molecules through nanopores with salt gradients: the role of osmotic flow. Phys Rev Lett 107:068101

    Article  Google Scholar 

  39. Wells DB, Abramkina V, Aksimentiev A (2007) Exploring transmembrane transport through alpha-hemolysin with grid-steered molecular dynamics. J Chem Phys 127:125101

    Article  Google Scholar 

  40. Butler TZ, Pavlenok M, Derrington IM et al (2008) Single-molecule DNA detection with an engineered Mspa protein nanopore. Proc Natl Acad Sci USA 105:20647–20652

    Article  Google Scholar 

  41. Derrington IM, Butler TZ, Collins MD et al (2010) Nanopore DNA sequencing with Mspa. Proc Natl Acad Sci USA 107:16060–16065

    Article  Google Scholar 

  42. Aksimentiev A, Heng JB, Timp G et al (2004) Microscopic kinetics of DNA translocation through synthetic nanopores. Biophys J 87:2086–2097

    Article  Google Scholar 

  43. Comer J, Dimitrov V, Zhao Q et al (2009) Microscopic mechanics of hairpin DNA translocation through synthetic nanopores. Biophys J 96:593–608

    Article  Google Scholar 

  44. Schneider GF, Kowalczyk SW, Calado VE et al (2010) DNA translocation through graphene nanopores. Nano Lett 10:3163–3167

    Article  Google Scholar 

  45. Siwy ZS, Davenport M (2010) Nanopores graphene opens up to DNA. Nat Nanotechnol 5:697–698

    Article  Google Scholar 

  46. TraversiF RaillonC, Benameur SM et al (2013) Detecting the translocation of DNA through a nanopore using graphene nanoribbons. Nat Nanotechnol 8:939–945

    Article  Google Scholar 

  47. Garaj S, Hubbard W, Reina A et al (2010) Graphene as a subnanometre trans-electrode membrane. Nature 467:190–193

    Article  Google Scholar 

  48. Wells DB, Belkin M, Comer J et al (2012) Assessing graphene nanopores for sequencing DNA. Nano Lett 12:4117–4123

    Article  Google Scholar 

  49. Sathe C, Zou X, Leburton JP et al (2011) Computational investigation of DNA detection using graphene nanopores. ACS Nano 5:8842–8851

    Article  Google Scholar 

  50. Liu JW (2012) Adsorption of DNA onto gold nanoparticles and graphene oxide: surface science and applications. Phys Chem Chem Phys 14:10485–10496

    Article  Google Scholar 

  51. Zhang X, Servos MR, Liu JW (2012) Surface science of DNA adsorption onto citrate-capped gold nanoparticles. Langmuir 28:3896–3902

    Article  Google Scholar 

  52. Zhang X, Liu BW, Servos MR et al (2013) Polarity control for nonthiolated DNA adsorption onto gold nanoparticles. Langmuir 29:6091–6098

    Article  Google Scholar 

  53. He H, Scheicher RH, Pandey R et al (2008) Functionalized nanopore-embedded electrodes for rapid DNA sequencing. J Phys Chem C 112:3456–3459

    Article  Google Scholar 

  54. Nelson T, Zhang B, Prezhdo OV (2010) Detection of nucleic acids with graphene nanopores: ab initio characterization of a novel sequencing device. Nano Lett 10:3237–3242

    Article  Google Scholar 

  55. Postma HWC (2010) Rapid sequencing of individual DNA molecules in graphene nanogaps. Nano Lett 10:420–425

    Article  Google Scholar 

  56. Wilson J, Di Ventra M (2013) Single-base DNA discrimination via transverse ionic transport. Nanotechnology 24:415101

    Article  Google Scholar 

  57. Shi XH, Yong K, Zhao YP et al (2005) Molecular dynamics simulation of peeling a DNA molecule on substrate. Acta Mech Sin 21:249–256

    Article  Google Scholar 

  58. Neuman KC, Nagy A (2008) Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopy. Nat Meth 5:491–505

    Article  Google Scholar 

  59. Spiering A, Getfert S, Sischka A et al (2011) Nanopore translocation dynamics of a single DNA-bound protein. Nano Lett 11:2978–2982

    Article  Google Scholar 

  60. Lulevich V, Kim S, Grigoropoulos CP et al (2011) Frictionless sliding of single-stranded DNA in a carbon nanotube pore observed by single molecule force spectroscopy. Nano Lett 11:1171–1176

    Article  Google Scholar 

  61. Zhang Z, Shen J, Wang H et al (2014) Effects of graphene nanopore geometry on DNA sequencing. J Phys Chem Lett 5:1602–1607

  62. Liu Q, Wu H, Wu L et al (2012) Voltage-driven translocation of DNA through a high throughput conical solid-state nanopore. PLoS One 7:e46014

    Article  Google Scholar 

  63. Meller A, Nivon L, Brandin E et al (2000) Rapid nanopore discrimination between single polynucleotide molecules. Proc Natl Acad Sci USA 97:1079–1084

    Article  Google Scholar 

  64. Kowalczyk SW, Wells DB, Aksimentiev A et al (2012) Slowing down DNA translocation through a nanopore in lithium chloride. Nano Lett 12:1038–1044

    Article  Google Scholar 

  65. Zhang Y, Liu L, Sha J et al (2013) Nanopore detection of DNA molecules in magnesium chloride solutions. Nanoscale Res Lett 8:245

    Article  Google Scholar 

  66. Fologea D, Uplinger J, Thomas B et al (2005) Slowing DNA translocation in a solid-state nanopore. Nano Lett 5:1734–1737

    Article  Google Scholar 

  67. Si W, Sha J, Liu L et al (2013) Effect of nanopore size on poly(dt)30 translocation through silicon nitride membrane. Sci China Technol Sci 56:2398–2402

    Article  Google Scholar 

  68. Utkur M, Jeffrey C, Valentin D et al (2010) Slowing the translocation of double-stranded DNA using a nanopore smaller than the double helix. Nanotechnology 21:395501

    Article  Google Scholar 

  69. Lu B, Hoogerheide DP, Zhao Q et al (2013) Pressure-controlled motion of single polymers through solid-state nanopores. Nano Lett 13:3048–3052

    Article  Google Scholar 

  70. Zhang H, Zhao Q, Tang Z et al (2013) Slowing down DNA translocation through solid-state nanopores by pressure. Small 9:4112–4117

    Article  Google Scholar 

  71. Manrao EA, Derrington IM, Laszlo AH et al (2012) Reading DNA at single-nucleotide resolution with a mutant mspa nanopore and Phi29 DNA polymerase. Nat Biotechnol 30:349–353

    Article  Google Scholar 

  72. Cherf GM, Lieberman KR, Rashid H et al (2012) Automated forward and reverse ratcheting of DNA in a nanopore at 5-Angstrom precision. Nat Biotechnol 30:344–348

    Article  Google Scholar 

  73. Olasagasti F, Lieberman KR, Benner S et al (2010) Replication of individual DNA molecules under electronic control using a protein nanopore. Nat Nanotechnol 5:798–806

    Article  Google Scholar 

  74. Lieberman KR, Cherf GM, Doody MJ et al (2010) Processive replication of single DNA molecules in a nanopore catalyzed by Phi29 DNA polymerase. J Am Chem Soc 132:17961–17972

    Article  Google Scholar 

  75. Hyun C, Kaur H, Rollings R et al (2013) Threading immobilized DNA molecules through a solid-state nanopore at >100 Μs per base rate. ACS Nano 7:5892–5900

    Article  Google Scholar 

  76. Luan B, Aksimentiev A (2010) Control and reversal of the electrophoretic force on DNA in a charged nanopore. J Phys Condens Matter 22:454123

    Article  Google Scholar 

  77. Sigalov G, Comer J, Timp G et al (2008) Detection of DNA sequences using an alternating electric field in a nanopore capacitor. Nano Lett 8:56–63

    Article  Google Scholar 

  78. Belkin M, Maffeo C, Wells DB et al (2013) Stretching and controlled motion of single-stranded DNA in locally heated solid-state nanopores. ACS Nano 7:6816–6824

    Article  Google Scholar 

  79. Avdoshenko SM, Nozaki D, Gomes da Rocha C et al (2013) Dynamic and electronic transport properties of DNA translocation through graphene nanopores. Nano Lett 13:1969–1976

    Article  Google Scholar 

  80. Luan BQ, Peng HB, Polonsky S et al (2010) Base-by-base ratcheting of single stranded DNA through a solid-state nanopore. Phys Rev Lett 104:238103

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Basic Research Program of China (2011CB707605) and the National Natural Science Foundation of China (50925519, 51375092).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments, Southeast University, Nanjing, 210096, China

    Wei Si, Yin Zhang, Gensheng Wu, Jingjie Sha, Lei Liu & Yunfei Chen

Authors
  1. Wei Si
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gensheng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jingjie Sha
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yunfei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yunfei Chen.

Additional information

SPECIAL TOPIC: Nanopore Analysis

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Si, W., Zhang, Y., Wu, G. et al. DNA sequencing technology based on nanopore sensors by theoretical calculations and simulations. Chin. Sci. Bull. 59, 4929–4941 (2014). https://doi.org/10.1007/s11434-014-0622-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11434-014-0622-x

Keywords

Search

Navigation