Background: The lungs are directly exposed to pollutants, pathogens, allergens, and chemicals, which might lead to physiological disorders. During the Bhopal gas disaster, the lungs of the victims were exposed to various chemicals. Here, using molecular modelling studies, we describe the effects of these chemicals (Dimethyl urea, Trimethyl urea, Trimethyl isocyanurate, Alphanaphthol, Butylated hydroxytoluene and Carbaryl) on pulmonary immune proteins.
Objectives: In the current study, we performed molecular modelling methods like molecular docking and molecular dynamics simulation studies to identify the effects of hydrolytic products of MIC and dumped residues on the pulmonary immune proteins.
Methods: Molecular docking studies of (Dimethyl urea, Trimethyl urea, Trimethyl isocyanurate, Alphanaphthol, Butylated hydroxytoluene and Carbaryl) on pulmonary immune proteins was performed using the Autodock 4.0 tool, and gromacs was used for the molecular dynamics simulation studies to get an insight into the possible mode of protein-ligand interactions. Further, in silico ADMET studies was performed using the TOPKAT protocol of discovery studio.
Results: From docking studies, we found that surfactant protein-D is inhibited most by the chemicals alphanaphthol (dock score, -5.41Kcal/mole), butylated hydroxytoluene (dock score,-6.86 Kcal/mole), and carbaryl (dock score,-6.1 Kcal/mole). To test their stability, the obtained dock poses were placed in a lipid bilayer model system mimicking the pulmonary surface. Molecular dynamics simulations suggest a stable interaction between surfactant protein-D and carbaryl.
Conclusion: This, study concludes that functioning of surfactant protein-D is directly or indirectly affected by the carbaryl chemical, which might account for the increased susceptibility of Bhopal gas disaster survivors to pulmonary tuberculosis.
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