Virtual screening and molecular dynamics simulation of compounds from the herbal database of Indonesia against histone deacetylase 2

Objective: This study aimed to find the herbal compounds from the database of Indonesian herbs with potential for use as histone deacetylase 2 (HDAC2) enzyme inhibitors through virtual screening using the LigandScout program. Methods: Virtual screening was conducted using LigandScout 4.09.3, AutodockZN, and AutoDockTools. Results: The virtual screening process resulted in 10 compounds with the highest pharmacophore fit score rating, from which five compounds with the best criteria for molecular dynamics simulations were selected: Boesenbergin B, pongachalcone I, 6,8-diprenylgenistein, marmin, and mangostin. The δG values obtained were, respectively, -8.28, -9.15, -7.05, -9.07, and -7.15. The active crystal ligand N-(2-aminophenyl) benzamide was used as a positive control, with δG value of -10.27. Molecular dynamic’s simulations showed that the activity of HDAC2 inhibitors was known to interact in the amino acid residues His145C, Tyr308C, Zn379C, Leu276C, Phe155C, Phe210C, Leu144C, and Met35C. Conclusions: Based on virtual screening and the molecular dynamics simulations, marmin was considered to provide the best overall activity of analysis. Simulation analysis of molecular dynamics from hits compound showed that analysis with MMGBSA gave higher free energy binding value than MMPBSA.