Open AccessVIRTUAL SCREENING AND MOLECULAR DYNAMICS SIMULATION OF COMPOUNDS FROM THE HERBAL DATABASE OF INDONESIA AGAINST HISTONE DEACETYLASE 2
Author(s) -
Muhammad Teguh Setiawan,
Arry Yanuar
Publication year - 2018
Publication title -
international journal of applied pharmaceutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.238
H-Index - 15
ISSN - 0975-7058
DOI - 10.22159/ijap.2018.v10s1.52
Subject(s) - virtual screening , pharmacophore , molecular dynamics , histone deacetylase , chemistry , computational biology , computational chemistry , stereochemistry , histone , biochemistry , biology , gene
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 withthe 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 asa positive control, with ΔG value of −10.27. Molecular dynamic’s simulations showed that the activity of HDAC2 inhibitors was known to interact inthe 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 ofanalysis. Simulation analysis of molecular dynamics from hits compound showed that analysis with MMGBSA gave higher free energy binding valuethan MMPBSA.