Molecular docking analysis and molecular dynamics simulation study of ameltolide analogous as a sodium channel blocker

Fifteen compounds related to ameltolide with sodium channel inhibitory activity were subjected to a molecular docking study. The chemical structures of all compounds were built using the program HyperChem and conformational studies were performed with a semiempirical method followed by the PM3 method. A docking study was performed using the program AutoDock on all the compounds. To confirm the binding mode of inhibitors, molecular dynamics simulations were performed using GROMACS 4.5.5, based upon the docked conformation of ameltolide. The docking analyses indicated that these compounds interacted mainly with residues II-S6 and III-S6 of NaV1.2 by making hydrogen bonds and ( π − π) interactions with domains I, III, and IV in the channel’s inner pore. Our docking study reveals that amide linker plays a major role in the drug–receptor interaction. The results of molecular dynamic simulations confirmed the binding mode of ligands, the accuracy of docking, and the reliability of active conformations obtained by AutoDock.