Atomic insight into designed carbamate-based derivatives as acetylcholine esterase (AChE) inhibitors: a computational study by multiple molecular docking and molecular dynamics simulation

Over 100 variants have been designed and studied, using multiple docking methods such as Autodock Vina, ArgusLab, Molegro Virtual Docker, and Hex-Cuda, to study the effect of alteration in the structure of carbamate-based acetylcholyne esterase (AChE) inhibitors. Sixteen selected systems were then subjected to 14 ns molecular dynamics (MD) simulations. Results from all the docking methods are in agreement. Variants that involved biphenyl substituents possess the most negative binding energies in the -37.64 to -39.31 kJ mol(-1) range due to their pi-pi interactions with AChE aromatic residues. The root mean square deviation values showed that all of these components achieved equilibration after 6 ns. Gyration radius (R-g) and solvent accessibility surface area were calculated to further investigate the AChE conformational changes in the presence of these components. MD simulation results suggested that these components might interact with AChE, possibly with no major changes in AChE secondary and tertiary structures.