Molecular Dynamics Investigation of the Interactions Between RNA Aptamer and Graphene-Monoxide/Boron-Nitride Surfaces: Applications to Novel Drug Delivery Systems

  • Mohaddeseh Habibzadeh Mashatooki
  • Jaber Jahanbin SardroodiEmail author
  • Alireza Rastkar Ebrahimzadeh


The interactions between RNA aptamer and boron nitride/graphene monoxide nanosheets were investigated using the molecular dynamics simulations. The potential capability of graphene monoxide and boron nitride surfaces to immobilize RNA aptamer was examined in detail. The distance between center of mass of RNA aptamer and the considered surfaces and root mean square deviation and fluctuation were calculated. The results suggest that the adsorption of RNA aptamer on the boron nitride surface is easily occurred compared to the adsorption on the graphene monoxide surface. Besides, RNA aptamer adsorption on the graphene monoxide nanosheet is energetically more favorable than that on the boron nitride one. The water molecules dipole moment and density profile were used to analyze water effect on the immobilization of aptamer on the GMO and BN surfaces. The results of all-atom molecular dynamics simulations show the higher ability of BN nanosheet for delivery application of this RNA aptamer.

Graphical Abstract


Nanosheet Biocompatible RNA aptamer Molecular dynamics 



This work has been supported by Azarbaijan Shahid Madani University. [Grant number 214/D/25972]. The authors thank to Dr. Amirali Abbasi for valuable discussions and suggestions.


  1. 1.
    K.S. Novoselov, A.K. Geim, S.V. Morozov, D. Jiang, M.I. Katsnelson, I.V. Grigorieva, S.V. Dubonos, and A.A. Firsov, Two-dimensional gas of massless dirac fermions in graphene. Nature 438, 197 (2005)CrossRefGoogle Scholar
  2. 2.
    K.S. Novoselov, A.K. Geim, S.V. Morozov, D. Jiang, Y. Zhang, S.V. Dubonos, I.V. Grigorieva, A.A. Firsov, Electric field effect in atomically thin carbon films. Science 306, 666–669 (2004)CrossRefGoogle Scholar
  3. 3.
    Y.B. Zhang, Y.W. Tan, H.L. Stormer, P. Kim, Experimental observation of the quantum hall effect and berry’s phase in graphene. Nature 438, 201–204 (2005)CrossRefGoogle Scholar
  4. 4.
    J.C. Meyer, A.K. Geim, M.I. Katsnelson, K.S. Novoselov, T.J. Booth, S. Roth, The structure of suspended graphene sheets. Nature 446, 60–63 (2007)CrossRefGoogle Scholar
  5. 5.
    M.Y. Han, B.O¨ zyilmaz, Y. Zhang, P. Kim, Energy band-gap engineering of graphene nanoribbons. Phys. Rev. Lett. 98, 206805 (2007)CrossRefGoogle Scholar
  6. 6.
    A. Rycerz, Random matrices and quantum chaos in weakly disordered graphene nanoflakes. Phys. Rev. B 85, 245424 (2012)CrossRefGoogle Scholar
  7. 7.
    E. Rasanen, C.A. Rozzi, S. Pittalis, G. Vignale, arXiv:1201.1734v3Google Scholar
  8. 8.
    B.-L. Huang, M.-C. Chang, C.-Y. Mou, Persistent currents in a graphene ring with armchair edges. J. Phys. 24, 245304 (2012)Google Scholar
  9. 9.
    N.V. Hung, F. Mazzamuto, A. Bournel, P. Dollfus, Resonant tunneling diode based on graphene/h-BN heterostructure. J. Phys. D 45, 325104 (2012)CrossRefGoogle Scholar
  10. 10.
    Z. Liu, W.B. Cai, L. He, N. Nakayama, K. Chen, X.M. Sun, X.Y. Chen, H.J. Dai, In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nat. Nanotechnol. 2, 47–52 (2007)CrossRefGoogle Scholar
  11. 11.
    Z. Liu, S. Tabakman, K. Welsher, H.J. Dai, Carbon nanotubes in biology and medicine: in vitro and in vivo detection, imaging and drug delivery. Nano Res. 2, 85–120 (2009)CrossRefGoogle Scholar
  12. 12.
    R.H. Zhou, H.J. Gao, Cytotoxicity of graphene: Recent advances and future perspective. Wiley Interdiscip. Rev. 6, 452–474 (2014)Google Scholar
  13. 13.
    A. Sasidharan, L.S. Panchakarla, P. Chandran, D. Menon, S. Nair, C.N.R. Rao, M. Koyakutty, Differential nano-bio interactions and toxicity effects of pristine versus functionalized graphene. Nanoscale 3, 2461–2464 (2011)CrossRefGoogle Scholar
  14. 14.
    K. Andre Mkhoyan, A.W. Contryman, J. Silcox, D.A. Stewart, G. Eda, C. Mattevi, S. Miller, M. Chhowalla, Atomic and electronic structure of graphene-oxide. Nano Lett. 9(3), 1058–1063 (2009)CrossRefGoogle Scholar
  15. 15.
    S. Park, J.W. Suk, J. An, J. Oh, S. Lee, W. Lee, J.R. Potts, J.-H. Byunc, R.S. Ruoff, The effect of concentration of graphene nanoplatelets on mechanical and electrical properties of reduced graphene oxide papers. Carbon 50(12), 4573–4578, (2012)CrossRefGoogle Scholar
  16. 16.
    K. Yang, S. Zhang, G.X. Zhang, X.M. Sun, S.T. Lee, Z. Liu, Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy. Nano Lett. 10, 3318–3323 (2010)CrossRefGoogle Scholar
  17. 17.
    S.B. Liu, T.H. Zeng, M. Hofmann, E. Burcombe, J. Wei, R.R. Jiang, J. Kong, Y. Chen, Antibacterial activity of graphite, graphite oxide, graphene oxide, and reduced graphene oxide: membrane and oxidative stress. ACS Nano 5, 6971–6980 (2011)CrossRefGoogle Scholar
  18. 18.
    A.M. Pinto, I.C. Gonçalves, F.D. Magalhães, Graphenebased materials biocompatibility: a review. Colloids Surf. B 111, 188–202 (2013)CrossRefGoogle Scholar
  19. 19.
    H. Bai, C. Li, G.Q. Shi, Functional composite materials based on chemically converted graphene. Adv. Mater 23, 1089–1115 (2011)CrossRefGoogle Scholar
  20. 20.
    E.C. Mattson, H. Pu, S. Cui, et al., Evidence of nanocrystalline semiconducting graphene monoxide during thermal reduction of graphene oxide in vacuum. ACS Nano 5(12), 9710–9717 (2011)CrossRefGoogle Scholar
  21. 21.
    D.R. Dreyer, S. Park, C.W. Bielawski, R.S. Ruoff, TheChemistry of Graphene Oxide. Chem. Soc. Rev. 39, 228–240 (2010)CrossRefGoogle Scholar
  22. 22.
    M. Acik, G. Lee, C. Mattevi, M. Chhowalla, K. Cho, Y.J. Chabal, Unusual infrared-absorption mechanism in thermally reduced graphene oxide. Nat. Mater. 9, 840–845 (2010)CrossRefGoogle Scholar
  23. 23.
    A. Bagri, C. Mattevi, M. Acik, Y.J. Chabal, M. Chhowalla, V.B. Shenoy, Structural evolution during the reduction of chemically derived graphene oxide. Nat. Chem. 2, 581–587 (2010)CrossRefGoogle Scholar
  24. 24.
    M. Acik, C. Mattevi, C. Gong, G. Lee, K. Cho, M. Chhowalla, Y.J. Chabal, The role of intercalated water in multilayered graphene oxide. ACS Nano 4, 5861–5868 (2010)CrossRefGoogle Scholar
  25. 25.
    G. Yang, Y. Zhang, X. Yan, Electronic structure and optical properties of graphene monoxide. J. Semicond. 34, 83004–83021 (2013)CrossRefGoogle Scholar
  26. 26.
    M. Atabay, J.J. Sardroodi, A.R. Ebrahimzadeh, Adsorption and immobilisation of human insulin on graphene monoxide, silicon carbide and boron nitride nanosheets investigated by molecular dynamics simulation. Mol. Simulat. 43, 298–311 (2017)CrossRefGoogle Scholar
  27. 27.
    D. Pacilé, J.C. Meyer, ÇÖ Girit, A. Zettl, The two dimensional phase of boron nitride: few-atomic-layer sheets and suspended membranes. Appl. Phys. Lett. 92, 133107 (2008)CrossRefGoogle Scholar
  28. 28.
    C.Y. Zhi, Y. Bando, C.C. Tang, H. Kuwahara, D. Golberg, Large-scale fabrication of boron nitride nanosheets and their utilization in polymeric composites with improved thermal and mechanical properties. Adv. Mater. 21, 2889–2893 (2009)CrossRefGoogle Scholar
  29. 29.
    C.K. Yang, Exploring the interaction between the boron nitride nanotube and biological molecules. Comput. Phys. Commun. 182, 39–42 (2011)CrossRefGoogle Scholar
  30. 30.
    M. Thomas, M. Enciso, T.A. Hilder, Insertion mechanism and stability of boron nitride nanotubes in lipid bilayers. J. Phys. Chem. B 119, 4929–4936 (2015)CrossRefGoogle Scholar
  31. 31.
    T.A. Hilder, N. Gaston, Interaction of boron nitride nanosheets with model cell membranes. ChemPhysChem 17, 1573–1578 (2016)CrossRefGoogle Scholar
  32. 32.
    S. Mateti, C.S. Wong, Z. Liu, W. Yang, Y. Li, L.H. Li, Y. Chen, Biocompatibility of boron nitride nanosheets. Nano Res. 11, 334–342 (2017)Google Scholar
  33. 33.
    H.M. Ghassemi, C.H. Lee, Y.K. Yap, R.S. Yassar, In situ TEM monitoring of thermal decomposition in individual boron nitride nanotubes, JOM, 62, 62–69 (2010)CrossRefGoogle Scholar
  34. 34.
    G. Ciofani, V. Raffa, J. Yu, Y. Chen, Y. Obata, S. Takeoka, A. Menciassi, A. Cuschieri, Boron nitride nanotubes: a novel vector for targeted magnetic drug delivery. Curr. Nanosci. 5, 33–38 (2009)CrossRefGoogle Scholar
  35. 35.
    G. Ciofani, V. Raffa, A. Menciassi, A. Cuschieri, Boron nitride nanotubes: an innovative tool for nanomedicine. Nano Today 4, 8–10 (2009)CrossRefGoogle Scholar
  36. 36.
    A. Abbasi, J.J. Sardroodi, An innovative method for the removal of toxic SOx molecules from environment by TiO2/Stanene nanocomposites: a first-principles study. J. Inorg. Organomet. Polym. 28, 1901–1913 (2018)CrossRefGoogle Scholar
  37. 37.
    A. Abbasi, J.J. Sardroodi, Exploration of sensing of nitrogen dioxide and ozone molecules using novel TiO2/Stanene heterostructures employing DFT calculations. Appl. Surf. Sci. 442, 368–381 (2018)CrossRefGoogle Scholar
  38. 38.
    A. Abbasi, J.J. Sardroodi, A highly sensitive chemical gas detecting device based on N-doped ZnO as a modified nanostructure media: a DFT + NBO analysis. Surf. Sci. 668, 150–163 (2018)CrossRefGoogle Scholar
  39. 39.
    N.S. Que-Gewirth, B.A. Sullenger, Gene therapy progress and prospects: RNA aptamers. Gene Ther. 14, 283–291 (2007)CrossRefGoogle Scholar
  40. 40.
    D.B. Huang, D. Vu, L.A. Cassiday, J.M. Zimmerman, L.J. Maher III, G. Ghosh, Crystal structure of NF-kappaB (p50)2 complexed to a high-affinity RNA aptamer. Proc. Natl. Acad. Sci. USA 100, 9268–9273 (2003)CrossRefGoogle Scholar
  41. 41.
    C.P. Rusconi, J.D. Roberts, G.A. Pitoc, S.M. Nimjee, R.R. White, G. Quick Jr., et al., Antidote-mediated control of an anticoagulant aptamer in vivo. Nat Biotechnol 22, 1423–1428 (2004)CrossRefGoogle Scholar
  42. 42.
    S. Santulli-Marotto, S.K. Nair, C. Rusconi, B. Sullenger, E. Gilboa, Multivalent RNA aptamers that inhibit CTLA-4 and enhance tumor immunity. Cancer Res. 63, 7483–7489 (2003)Google Scholar
  43. 43.
    X. Yu, S. Ghamande, H. Liu, L. Xue, S. Zhao, W. Tan, L. Zhao, S.C. Tang, D. Wu, H. Korkaya, N.J. Maihle, H.Y. Liu, Targeting EGFR/HER2/HER3 with a three-in-one aptamer-siRNA chimera confers superior activity against HER2+ breast cancer. Mol. Ther. Nucleic Acids. 10, 317–330 (2018). CrossRefGoogle Scholar
  44. 44.
    V. Romanucci, A. Zarrelli, S. Liekens, S. Noppen, C. Pannecouque, G. Di Fabio, New findings on the d(TGGGAG) sequence: Surprising anti-HIV-1 activity. Eur. J. Med. Chem. 145, 425–430 (2018). CrossRefGoogle Scholar
  45. 45.
    J. Bala, S. Chinnapaiyan, R.K. Dutta, H. Unwalla, Aptamers in HIV research diagnosis and therapy. RNA Biol. 15, 327–337 (2018). CrossRefGoogle Scholar
  46. 46.
    J.L. Henri, J. Macdonald, M. Strom, W. Duan, S. Shigdar, Aptamers as potential therapeutic agents for ovarian cancer. Biochimie. 145, 34–44 (2018). CrossRefGoogle Scholar
  47. 47.
    A. Bouvier-Müller, F. Ducongé, Nucleic acid aptamers for neurodegenerative diseases. Biochimie. 145, 73–83 (2018). CrossRefGoogle Scholar
  48. 48.
    J.I. Jung, S.R. Han, S.W. Lee, Development of RNA aptamer that inhibits methyltransferase activity of dengue virus. Biotechnol. Lett. 40, 315–324 (2018). CrossRefGoogle Scholar
  49. 49.
    M. Chakravarthy, H. AlShamaileh, H. Huang, R.K. Tannenberg, S. Chen, S. Worrall, P.R. Dodd, R.N. Veedu, Development of DNA aptamers targeting low-molecular-weight amyloid-β peptide aggregates in vitro. Chem. Commun. 54, 4593–4596 (2018). CrossRefGoogle Scholar
  50. 50.
    M. Yang, D. Xu, L. Jiang, L. Zhang, D. Dustin, R. Lund, L. Liu, H. Dong, Filamentous supramolecular peptide-drug conjugates as highly efficient drug delivery vehicles. Chem. Commun. 50, 4827 (2014)CrossRefGoogle Scholar
  51. 51.
    L. Liu, L. Zhang, Z. Sun, G. Xi, Graphene nanoribbon-guided fluid channel: a fast transporter of nanofluids. Nanoscale 4, 6279 (2012)CrossRefGoogle Scholar
  52. 52.
    L. Zhang, Z. Bai, L. Liu, Exceptional thermal conductance across hydrogen–bonded graphene/polymer interfaces, Adv. Mater. Interfaces, 3, 1600211 (2016)CrossRefGoogle Scholar
  53. 53.
    American Mineralogist Crystal Structure Database, 2018 (n.d.). (accessed June 8)
  54. 54.
    S. Fleming, A. Rohl, GDIS: a visualization program for molecular and periodic systems. Z. Für Krist. Cryst. Mater. 220, 580-584. Google Scholar
  55. 55.
    W. Humphrey, A. Dalke, K. Schulten, VMD: visual molecular dynamics. J. Mol. Graph. 14, 33–38 (1996). CrossRefGoogle Scholar
  56. 56.
    N. Li, H.H. Nguyen, M. Byrom, A.D. Ellington, Inhibition of cell proliferation by an anti-EGFR aptamer. PLoS ONE 6, e20299 (2011)CrossRefGoogle Scholar
  57. 57.
    A. Xayaphoummine, T. Bucher, H. Isambert, Kinefold web server for RNA/DNA folding path and structure prediction including pseudoknots and knots. Nucleic Acids Res. 33, W605–W610 (2005). CrossRefGoogle Scholar
  58. 58.
    M. Magnus, M.J. Boniecki, W. Dawson, J.M. Bujnicki, SimRNAweb: a web server for RNA 3D structure modeling with optional restraints. Nucleic Acids Res. 44, 315–319 (2016). CrossRefGoogle Scholar
  59. 59.
    J.C. Phillips, R. Braun, W. Wang, J. Gumbart, E. Tajkhorshid, E. Villa, C. Chipot, R.D. Skeel, L. Kalé, K. Schulten, Scalable molecular dynamics with NAMD. J. Comput. Chem. 26, 1781–1802 (2005). CrossRefGoogle Scholar
  60. 60.
    K. Vanommeslaeghe, E. Hatcher, C. Acharya, S. Kundu, S. Zhong, J. Shim, E. Darian, A.D. Mackerell, CHARMM general force field: a force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J. Comput. Chem. (2009). Google Scholar
  61. 61.
    L. Ningbo, Z. Beirong, Z. Hongming, X. Wei, First principle investigation on structural and electronic properties of silicon oxycarbide ceramics. J. Alloys Compd. 647, 665–669 (2015)CrossRefGoogle Scholar
  62. 62.
    L. Ningbo, X. Wei, Z. Hongming, Z. Miao, Molecular dynamics investigation of structure and high-temperature mechanical properties of SiBCO ceramics. J. Alloys Compd. 610, 45–49 (2014)CrossRefGoogle Scholar
  63. 63.
    L. Ningbo, Z. Beirong, Z. Hongming, X. Wei, Effect of carbon segregation on performance of inhomogeneous SiCyO6/5 as anode materials for lithium-ion battery: a first-principles study. J. Power Sources 334, 39–43 (2016)CrossRefGoogle Scholar
  64. 64.
    R. Kubo, M. Toda, N. Hashitsume, Statistical Physics II: Nonequilibrium Statistical Mechanics, 2nd edn. (Springer, New York, 1991)CrossRefGoogle Scholar
  65. 65.
    S.E. Feller, Y. Zhang, R.W. Pastor, B.R. Brooks, Constant pressure molecular dynamics simulation: the Langevin piston method. J. Chem. Phys. 103, 4613 (1995)CrossRefGoogle Scholar
  66. 66.
    J. Azamat, J.J. Sardroodi, A. Rastkar, Molecular dynamics simulation of ion separation and water transport trough boron nitride nanotubes. Desalination Water Treat. 56, 1090–1098 (2015)CrossRefGoogle Scholar
  67. 67.
    L. Zhang, T. chen, H. Ban, L. Liu, Hydrogen bonding-assisted thermal conduction in beta-sheet crystals of spider silk protein. Nanoscale 6, 7786–7791 (2014)CrossRefGoogle Scholar
  68. 68.
    L. Zhang, Z. Baj, H. Ban, L. Liu, Effects of the amino acid sequence on thermal conduction through ß-sheet crystals of natural silk protein. Phys. Chem. Chem. Phys. 17, 29007–29013 (2015)CrossRefGoogle Scholar
  69. 69.
    D.A. McQuarrie, Statistical thermodynamics, Univ. Sci. Books (1984)Google Scholar
  70. 70.
    K. Xu, J. Jicheng Zhang, X. Xiaoli Hao, C. Chunbo Zhang, N. Ning Wei, C. Zhang, Wetting properties of defective graphene oxide: a molecular simulation study. Molecules 23, 1439 (2018). CrossRefGoogle Scholar
  71. 71.
    J.M. Healy, S.D. Lewis, M. Kurz, R.M. Boomer, K.M. Thompson, C. Wilson et al., Pharmacokinetics and biodistribution of novel aptamer compositions. Pharm. Res. 21, 2234–2246 (2004)CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Mohaddeseh Habibzadeh Mashatooki
    • 1
    • 2
    • 3
  • Jaber Jahanbin Sardroodi
    • 1
    • 2
    • 3
    Email author
  • Alireza Rastkar Ebrahimzadeh
    • 1
    • 2
    • 4
  1. 1.Molecular Simulation laboratory (MSL)Azarbaijan Shahid Madani UniversityTabrizIran
  2. 2.Computational Nanomaterials Research Group (CNRG)Azarbaijan Shahid Madani UniversityTabrizIran
  3. 3.Department of Chemistry, Faculty of Basic SciencesAzarbaijan Shahid Madani UniversityTabrizIran
  4. 4.Department of Physics, Faculty of Basic SciencesAzarbaijan Shahid Madani UniversityTabrizIran

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