Molecular docking and dynamics studies of cigarette smoke carcinogens interacting with acetylcholinesterase and butyrylcholinesterase enzymes of the central nervous system.

The free radicals produced by cigarette smoking are responsible for tissue damage, heart and lung diseases, and carcinogenesis. The effect of tobacco on the central nervous system (CNS) has received increased attention nowadays in research. Therefore, to explore the molecular interaction of cigarette smoke carcinogens (CSC) 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanol (NNAL), 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK), and N'-nitrosonornicotine (NNN) with well-known targets of CNS-related disorders, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes, a cascade of the computational study was conducted including molecular docking and molecular dynamics simulations (MDS). The investigated results of NNAL+AChEcomplex, NNK+AChEcomplex, and NNK+BuChEcomplex based on intermolecular energies (∆G) were found to -8.57 kcal/mol, -8.21 kcal/mol, and -8.08 kcal/mol, respectively. MDS deviation and fluctuation plots of the NNAL and NNK interaction with AChE and BuChE have shown significant results. Further, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) results shown the best total binding energy (Binding∆G) -87.381 (+/-13.119) kJ/mol during NNK interaction with AChE. Our study suggests that CSC is well capable of altering the normal biomolecular mechanism of CNS; thus, obtained data could be useful to design extensive wet laboratory experimentation to know the effects of CSC on human CNS.