title: Insights from the Molecular Docking of Hydrolytic Products of Methyl Isocyanate (MIC) to Inhibition of Human Immune Proteins.
abstract: 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 [Formula: see text] G [Formula: see text]3.51, [Formula: see text]3.79, [Formula: see text]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.
authors: Department of Biological Sciences and Engineering, Maulana Azad National Institute of Technology, Bhopal, 462051, India.
authors: Manish Kumar
authors: MK
authors: Tripathi
authors: Department of Biological Sciences and Engineering, Maulana Azad National Institute of Technology, Bhopal, 462051, India.
authors: Mohammad
authors: M
authors: Yasir
authors: Department of Research, Bhopal Memorial Hospital and Research Centre, Bhopal, 462023, India.
authors: Vikram Singh
authors: VS
authors: Gurjar
authors: Department of Research, Bhopal Memorial Hospital and Research Centre, Bhopal, 462023, India.
authors: Protiti
authors: P
authors: Bose
authors: Department of Chemistry, Maulana Azad National Institute of Technology, Bhopal, 462051, India.
authors: Amit
authors: A
authors: Dubey
authors: Department of Biological Sciences and Engineering, Maulana Azad National Institute of Technology, Bhopal, 462051, India. shrivastavarm@manit.ac.in.
authors: Rahul
authors: R
authors: Shrivastava
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D020134:Catalytic Domain; D006801:Humans; D006868:Hydrolysis; D007107:Immune System / Q000378:metabolism*; D017953:Isocyanates / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011506:Proteins / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D017953:Isocyanates; D008024:Ligands; D011506:Proteins; C008461:methyl isocyanate
keywords: Hydrolytic product; Immune suppression; Methyl isocyanate; Molecular docking; Mycobacterium tuberculosis