• Krishna Pal Singh Department of Amity Institute of Biotechnology, Amity University, Uttar Pradesh, India
  • Anupam Dhasmana Department of Himalayan School of Biosciences, Swami Rama Himalayan University, Dehradun, Uttarakhand, India.
  • Qamar Rahman Department of Amity Institute of Biotechnology, Amity University, Uttar Pradesh, India


 Objective: At present, toxicological tests are resource-intensive, time-consuming and require a large pool of animal models for toxicity assessment. To speed up the toxicity evaluation and to reduce animal suffering during toxicity assessment, the use of alternative methods including computational models is in high demand. The computational toxicity prediction methods are very helpful for the regulatory bodies to quickly assess the health impact of nanomaterial materials. In the present work, we have examined the mechanism of zinc oxide nanoparticle (ZnO-NP)-proteins interaction and their effect of surface chemistries of ZnO-NP on the bioactive conformation of chemokines and other cytological proteins using in silico molecular docking approaches.

Methods: Molecular docking study was conducted using AutoDock 4.0 version and the visualization result using Discover Studio 4.0.

Results: In the present study, we observed that ZnO-NP has high binding affinity with the mitogen-activated protein kinases (P-38), nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) proteins, and matrix metallopeptidase-9 with docking energies −8.81, −7.64, and −7.27 Kcal/ Mol, respectively, involving with hydrogen, metal acceptor, and electrostatic interaction. The top interacting amino acid residues with ZnO-NP are GLY, PHE, ARG, ASP, GLN, and ASN.

Conclusion: Thus, based on the molecular docking studies, we determine that the ZnO-NP is strongly interacting with the chemokines and other cytological proteins thus responsible for blocking of the activation stimuli for these proteins to initiate the biological signals for the proper functioning. The important interaction pattern ZnO-NP with the surface-enriched amino acid residues of chemokines and cytological proteins using molecular docking approach.

Keywords: Zinc oxide nanoparticle, Molecular docking, Nanoparticle-protein interaction, Toxicity.

Author Biography

Krishna Pal Singh, Department of Amity Institute of Biotechnology, Amity University, Uttar Pradesh, India
Assistant professor


1. Amelia M, Lincheneau C, Silvi S, Credi A. Electrochemical properties of cdSe and cdTe quantum dots. Chem Soc Rev 2012;41:5728-43.
2. Yan L, Zheng YB, Zhao F, Li S, Gao X, Xu B, et al. Chemistry and physics of a single atomic layer: Strategies and challenges for functionalization of graphene and graphene-based materials. Chem Soc Rev 2012;41:97-114.
3. Nel A, Xia T, Mädler L, Li N. Toxic potential of materials at the nanolevel. Science 2006;311:622-7.
4. Buzea C, Pacheco II, Robbie K. Nanomaterials and nanoparticles: Sources and toxicity. Biointerphases 2007;2:MR17-71.
5. De Stefano D, Carnuccio R, Maiuri MC. Nanomaterials toxicity and cell death modalities. J Drug Deliv 2012;2012:167896.
6. Oberdörster G. Nanotoxicology: In vitro-in vivo dosimetry. Environ Health Perspect 2012;120:A13.
7. Oberdörster G, Oberdörster E, Oberdörster J. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 2005;113:823-39.
8. Fan Z, Lu JG. Zinc oxide nanostructures: Synthesis and properties. J Nanosci Nanotechnol 2005;5:1561-73.
9. Nations S, Wages M, Cañas JE, Maul J, Theodorakis C, Cobb GP, et al. Acute effects of Fe2O3, TiO2, ZnO and CuO nanomaterials on Xenopus laevis. Chemosphere 2011;83:1053-61.
10. Jeng HA, Swanson J. Toxicity of metal oxide nanoparticles in mammalian cells. J Environ Sci Heal Part A 2006;41:2699-711.
11. Horie M, Nishio K, Fujita K, Endoh S, Miyauchi A, Saito Y, et al. Protein adsorption of ultrafine metal oxide and its influence on cytotoxicity toward cultured cells. Chem Res Toxicol 2009;22:543-53.
12. Wu W, Samet JM, Peden DB, Bromberg PA. Phosphorylation of p65 is required for zinc oxide nanoparticle–induced interleukin 8 EXPRESSION in human bronchial epithelial cells. Environ Health Perspect 2010;118:982-7.
13. Hackenberg S, Scherzed A, Technau A, Kessler M, Froelich K, Ginzkey C, et al. Cytotoxic, genotoxic and pro-inflammatory effects of zinc oxide nanoparticles in human nasal mucosa cells in vitro. Toxicol In Vitro 2011;25:657-63.
14. Babin K, Antoine F, Goncalves DM, Girard D. TiO2, ceO2 and znO nanoparticles and modulation of the degranulation process in human neutrophils. Toxicol Lett 2013;221:57-63.
15. Yuan L, Wang Y, Wang J, Xiao H, Liu X. Additive effect of zinc oxide nanoparticles and isoorientin on apoptosis in human hepatoma cell line. Toxicol Lett 2014;225:294-304.
16. Suzuki Y, Tada-Oikawa S, Ichihara G, Yabata M, Izuoka K, Suzuki M, et al. Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation. Toxicol Appl Pharmacol 2014;278:16-25.
17. Li CH, Liao PL, Shyu MK, Liu CW, Kao CC, Huang SH, et al. Zinc oxide nanoparticles–induced intercellular adhesion molecule 1 expression requires Rac1/Cdc42, mixed lineage kinase 3, and c-Jun N-terminal kinase activation in endothelial cells. Toxicol Sci 2012;126:162-72.
18. Sharma V, Anderson D, Dhawan A. Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2). Apoptosis 2012;17:852-70.
19. Song J, Du L, Feng Y, Wu W, Yan Z. Pyroptosis induced by zinc oxide nanoparticles in A549 cells. Wei Sheng Yan Jiu 2013;42:273-6.
20. Chuang KJ, Lee KY, Pan CH, Lai CH, Lin LY, Ho SC, et al. Effects of zinc oxide nanoparticles on human coronary artery endothelial cells. Food Chem Toxicol 2016;93:138-44.
21. Umrani RD, Paknikar KM. Zinc oxide nanoparticles show antidiabetic activity in streptozotocin-induced type 1 and 2 diabetic rats. Nanomedicine (Lond) 2014;9:89-104.
22. Pandurangan M, Veerappan M, Kim DH. Cytotoxicity of zinc oxide nanoparticles on antioxidant enzyme activities and mRNA expression in the cocultured C2C12 and 3T3-L1 cells. Appl Biochem Biotechnol 2015;175:1270-80.
23. Kumar A, Dhawan A, Shanker R. The need for novel approaches in ecotoxicity of engineered nanomaterials. J Biomed Nanotechnol 2011;7:79-80.
24. Ranjan S, Dasgupta N, Chinnappan S, Ramalingam C, Kumar A. A novel approach to evaluate titanium dioxide nanoparticle–protein interaction through docking: An insight into mechanism of action. Proc Natl Acad Sci India Sect B Biol Sci 2015;87:937-43.
25. Yang J, Roy A, Zhang Y. BioLiP: A semi-manually curated database for biologically relevant ligand-protein interactions. Nucleic Acids Res 2013;41:D1096-103.
26. Rahman S, Farooqui SA, Rai A, Kumar R, Santra C, Prabhakaran VC, et al. Mesoporous TUD-1 supported indium oxide nanoparticles for epoxidation of styrene using molecular O2. RSC Adv 2015;5:46850-60.
27. Sahare P, Moon A. In silico modelling of β-lactam resistant enterococcus faecalis pbp4 and its interactions with various phyto-ligands. Int J Pharm Pharm Sci 2016;8:151-5.
28. Dharani R, Ranjitha R, Sripathi R, Ali Muhammad KS, Ravi S. Docking studies in target proteins involved in antibacterial action mechanisms: Alkaloids isolated from Scutellaria genus. Asian J Pharm Clin Res 2016;9:121-5.
29. Morris GM, Goodsell DS, Huey R, Olson AJ. Distributed automated docking of flexible ligands to proteins: Parallel applications of autoDock 2.4. J Comput Aided Mol Des 1996;10:293-304.
30. Benyamini H, Shulman-Peleg A, Wolfson HJ, Belgorodsky B, Fadeev L, Gozin M. Interaction of C60-Fullerene and carboxyfullerene with proteins: Docking and binding site alignment. Bioconjug Chem 2006;17:378-86.
31. Baweja L, Gurbani D, Shanker R, Pandey AK, Subramanian V, Dhawan A, et al. C60-fullerene binds with the ATP binding domain of human DNA topoiosmerase II alpha. J Biomed Nanotechnol 2011;7:177-8.
32. Patel A, Smita S, Rahman Q, Gupta SK, Verma MK. Single wall carbon nanotubes block ion passage in mechano-sensitive ion channels by interacting with extracellular domain. J Biomed Nanotechnol 2011;7:183-5.
33. Goodsell DS, Morris GM, Olson AJ. Automated docking of flexible ligands: Applications of auto dock. J Mol Recognit 1996;9:1–5.
34. Xiao X, Mruk DD, Cheng CY. Intercellular adhesion molecules (ICAMs) and spermatogenesis. Hum Reprod Update 2013;19:167-86.
35. Bai R, Yi S, Zhang X, Liu H, Fang X. Role of ICAM-1 polymorphisms (G241R, K469E) in mediating its single-molecule binding ability: Atomic force microscopy measurements on living cells. Biochem Biophys Res Commun 2014;448:372-8.
36. Kao YT, Hsu WC, Hu HT, Hsu SH, Lin CS, Chiu CC, et al. Involvement of p38 mitogen-activated protein kinase in acquired gemcitabine-resistant human urothelial carcinoma sublines. Kaohsiung J Med Sci 2014;30:323-30.
37. Javadov S, Jang S, Agostini B. Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: Therapeutic perspectives. Pharmacol Ther 2014;144:202-25.
38. Pavlová S, Klucska K, Vašíček D, Ryban L, Harrath AH, Alwasel SH, et al. The involvement of SIRT1 and transcription factor NF-κB (p50/ p65) in regulation of porcine ovarian cell function. Anim Reprod Sci 2013;140:180-8.
39. Marinho HS, Real C, Cyrne L, Soares H, Antunes F. Hydrogen peroxide sensing, signaling and regulation of transcription factors. Redox Biol 2014;2:535-62.
40. Colvin VL. The potential environmental impact of engineered nanomaterials. Nat Biotechnol 2003;21:1166-70.
41. Hayden MS, West AP, Ghosh S. NF-κB and the immune response. Oncogene 2006;25:6758-6780.
42. Jin J, Hu H, Li HS, Yu J, Xiao Y, Brittain GC, et al. Noncanonical NF- κB pathway controls the production of Type I interferons in antiviral innate immunity. Immunity 2014;40:342-54.
43. Kain J, Karlsson HL, Möller L. DNA damage induced by micro-and nanoparticles – interaction with FPG influences the detection of DNA oxidation in the comet assay. Mutagenesis 2012;27:491-500.
44. Magdolenova Z, Collins A, Kumar A, Dhawan A, Stone V, Dusinska M, et al. Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology 2014;8:233-78.
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How to Cite
Singh, K. P., A. Dhasmana, and Q. Rahman. “ELUCIDATION THE TOXICITY MECHANISM OF ZINC OXIDE NANOPARTICLE USING MOLECULAR DOCKING APPROACH WITH PROTEINS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 3, Mar. 2018, pp. 441-6, doi:10.22159/ajpcr.2018.v11i3.23384.
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