Insights from the Molecular Docking of Hydrolytic Products of Methyl Isocyanate (MIC) to Inhibition of Human Immune Proteins

  • Manish Kumar Tripathi
  • Mohammad Yasir
  • Vikram Singh Gurjar
  • Protiti Bose
  • Amit Dubey
  • Rahul ShrivastavaEmail author
Original Research Article


This study is an attempt to find the reason for immunological suppression in victims of Bhopal gas tragedy during 1984 against Mycobacterium tuberculosis (Mtb) infection. Here, we tried to understand this problem by studying interactions between immune proteins associated with susceptibility to tuberculosis and hydrolytic products of methyl isocyanate (MIC) released during the tragedy. The hydrolytic products of MIC i.e. dimethyl urea, trimethyl urea and trimethyl isocyanurate were docked to different human immune proteins against Mtb using AutoDock 4.0. Results shows that all hydrolytic products (dimethyl urea, trimethyl urea and trimethylisocyanurate) strongly inhibit to CD40 ligand, and their binding energies were found to be \(\Delta\)G\(-\)3.51, \(-\)3.79, \(-\)4.55 (Kcal/mole), respectively. Further, to check the stability of docked complex, we performed the molecular dynamics simulation study which also shows that CD40 Ligand was maximally inhibited by trimethylisocyanurate and has a role in the macrophage activation for the destruction of M. tuberculosis. The present study may lead to better understanding of human immune protein inhibition by hydrolytic product of MIC.


Methyl isocyanate Hydrolytic product Mycobacterium tuberculosis Molecular docking Immune suppression 


  1. 1.
    Shrivastava R, Punde RP, Deshpande S (2010) Molecular characterization and bioinformatics approach of tuberculosis infection prevalent in methyl isocyanate affected population in Bhopal. Pharmacologyonline 3:757–767Google Scholar
  2. 2.
    Inadera H (2006) The immune system as a target for environmental chemicals: xenoestrogens and other compounds. Toxicol Lett 164(3):191–206CrossRefGoogle Scholar
  3. 3.
    Fausta F, Kassiea F, Knasmüllerb S, Kevekordesc S, Mersch-Sundermanna V (2004) Use of primary blood cells for the assessment of exposure to occupational endotoxicants in human biomonitoring studies. Toxicology 198:341–350CrossRefGoogle Scholar
  4. 4.
    Mishra PK, Bhargava A, Pathak N, Desikan P, Maudar KK, Varshney S, Shrivastava R, Jain A (2011) Molecular surveillance of hepatitis and tuberculosis infection in a cohort exposed to methyl isocyanate. Int J Occup Med Environ Health 24:94–101CrossRefGoogle Scholar
  5. 5.
    Shrivastava R, Yasir M, Tripathi M, Singh P (2013) In silico interaction of methyl isocyanate with immune protein responsible for Mycobacterium tuberculosis infection using molecular docking. Toxicol Ind Health. doi: 10.1177/0748233713498447 CrossRefGoogle Scholar
  6. 6.
    Yang P, Ebbert JO, Sun Z, Weinshilboum RM (2006) Role of the glutathione metabolic pathway in lung cancer treatment and prognosis: a review. JCO 24(11):1761–1769CrossRefGoogle Scholar
  7. 7.
    Sabel MS, Yamada M, Kawaguchi Y, Chen FA, Takita H, Bankert RB (2000) CD40 expression on human lung cancer correlates with metastatic spread. Cancer Immunol Immunother 49(2):101–108CrossRefGoogle Scholar
  8. 8.
    Ventura JJ, Tenbaum S, Perdiguero E, Huth M, Guerra C, Barbacid M, Pasparakis M, Nebreda AR (2007) P38\(\alpha\) MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat Genet 39:750–758CrossRefGoogle Scholar
  9. 9.
    Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (2007) AutoDock, Version 4.0.1: The Scripps Research Institute, La Jolla Google Scholar
  10. 10.
    Kinjo AR, Suzuki H, Yamashita R, Ikegawa Y, Kudou T, Igarashi R, Kengaku Y, Cho H, Standley DM, Nakagawaand A, Nakamura H (2012) Protein Data Bank Japan (PDBj): maintaining a structural data archive and resource description framework format. Nucl Acids Res 40:D453–D460CrossRefGoogle Scholar
  11. 11.
    Dundas J, Ouyang Z, Jeffery T, Andrew B, Yaron T, Liang J (2006) CASTp: computed atas of surface topography of proteins with structural and topographical mapping of functionally annotated residues. Nucl Acids Res 34:W116–W118CrossRefGoogle Scholar
  12. 12.
    O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison RG (2011) Open Babel: an open chemical toolbox. J Cheminf 3:33CrossRefGoogle Scholar
  13. 13.
    Berendsen HJC, Vander Spoel D, Van Drunen R (1995) GROMACS—a message passing parallel molecular dynamics implementation. Comp Phys Comm 91:43–56CrossRefGoogle Scholar
  14. 14.
    Lindah E, Hess B, Vander Spoel D (2001) Gromacs 3.0: a package for molecular simulation and trajectory analysis. J Mol Model 7:306–317CrossRefGoogle Scholar
  15. 15.
    Schuttelkopf AW, Van Aalten DMF (2004) PRODRG: a tool for high-throughput crystallography of protein-ligand complexes. Acta Cryst 60:1355–1363Google Scholar
  16. 16.
    Visconti R, Gadina M, Chiariello M, Chen EH, Stancato LF, Gutkind JS, O’Shea JJ (2000) Importance of the MKK6/P38 pathway for Interleukin-12-induced STAT4 serine phosphorylation and transcriptional activity. Blood 96:1844–1852PubMedGoogle Scholar
  17. 17.
    Hickman SP, Chan J, Salgame P (2002) Mycobacterium tuberculosis induces differential cytokine production from dendritic cells and macrophages with divergent effects on naive T Cell polarization. J Immunol 168:4636–4642CrossRefGoogle Scholar
  18. 18.
    Hewison M (2012) An update on Vitamin D and human immunity. ClinEndocrinol 76(3):315–325Google Scholar
  19. 19.
    White JH (2008) Vitamin D signaling, infectious diseases and regulation of innate immunity. Infect Immun 76(9):3837–3843CrossRefGoogle Scholar
  20. 20.
    Connell Nancy D, Venketaraman V (2009) Control of Mycobacterium tuberculosis infection by glutathione. Recent Pat Antiinfect Drug Discov 4(3):214–226CrossRefGoogle Scholar

Copyright information

© International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Manish Kumar Tripathi
    • 1
  • Mohammad Yasir
    • 1
  • Vikram Singh Gurjar
    • 2
  • Protiti Bose
    • 2
  • Amit Dubey
    • 3
  • Rahul Shrivastava
    • 1
    Email author
  1. 1.Department of Biological Sciences and EngineeringMaulana Azad National Institute of TechnologyBhopalIndia
  2. 2.Department of ResearchBhopal Memorial Hospital and Research CentreBhopalIndia
  3. 3.Department of ChemistryMaulana Azad National Institute of TechnologyBhopalIndia

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