VIRTUAL SCREENING AND MOLECULAR DYNAMICS SIMULATION OF COMPOUNDS FROM THE HERBAL DATABASE OF INDONESIA AGAINST HISTONE DEACETYLASE 2

Authors

  • Muhammad Teguh Setiawan Department of Biomedical Computation, Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, Indonesia.
  • Arry Yanuar Department of Biomedical Computation, Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, Indonesia.

DOI:

https://doi.org/10.22159/ijap.2018.v10s1.52

Keywords:

Histone deacetylase 2, Diabetes, Herbal database Indonesia, Molecular docking, Molecular dynamics simulation

Abstract

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.

Downloads

Download data is not yet available.

References

Ye J. Improving insulin sensitivity with HDAC inhibitor. Diabetes

;62:685-7.

Phamte H, Lethithu H. Integrating structure and ligand-base approaches

for modelling the histone deacetylase inhibition activity of hydroxamic

acid derivatives. Asian J Pharm Clin Res 2018;11:198-206.

Christensen DP, Dahllöf M, Lundh M, Rasmussen DN, Nielsen MD,

Billestrup N, et al. Histone deacetylase (HDAC) inhibition as a novel

treatment for diabetes mellitus. Mol Med 2011;17:378-90.

Patil SV, Mandare AP, Pandurang GB. Study of total cholesterol (TC),

tryacylglycerols (TG), high density lipoprotein cholesterol (HDL-C) in

Type II diabetes mellitus. Asian J Pharm Clin Res 2017;10:116-8.

Ministry of Health, Republic of Indonesia. Situation and Diabetes

Analysis. Jakarta: Data Center and Information, Ministry of Health,

Republic of Indonesia; 2014.

Al-Haddad R, Karnib N, Assaad RA, Bilen Y, Emmanuel N, Ghanem A,

et al. Epigenetic changes in diabetes. Neurosci Lett 2016;625:64-9.

Tanisa AA, Riadhi R, Yanuar A. Virtual screening of beta-secretase 1 (BASE1)

inhibitors in the Indonesian herbal database as using autodock and autodock

VNA. Asian J Pharm Clin Res 2017;10:148-52.

Fogolari F, Brigo A, Molinari H. Protocol for MM/PBSA molecular

dynamics simulations of proteins. Biophys J 2003;85:159-66.

Wolber G, Langer T. LigandScout: 3-D pharmacophores derived from

protein-bound ligands and their use as virtual screening filters. J Chem

Inf Model 2005;45:160-9.

Kästner J, Loeffler HH, Roberts SK, Martin-Fernandez ML, Winn MD.

Ectodomain orientation, conformational plasticity and oligomerization

of erbB1 receptors investigated by molecular dynamics. J Struct Biol

;167:117-28.

Desheng L, Jian G, Yuanhua C, Wei C, Huai Z, Mingjuan J,

et al. Molecular dynamics simulations and MM/GBSA methods to

investigate binding mechanisms of aminomethylpyrimidine inhibitors

with DPP-IV. Bioorg Med Chem Lett 2011;21:6630-5.

Published

20-12-2018

How to Cite

Setiawan, M. T., & Yanuar, A. (2018). VIRTUAL SCREENING AND MOLECULAR DYNAMICS SIMULATION OF COMPOUNDS FROM THE HERBAL DATABASE OF INDONESIA AGAINST HISTONE DEACETYLASE 2. International Journal of Applied Pharmaceutics, 10(1), 235–239. https://doi.org/10.22159/ijap.2018.v10s1.52

Issue

Section

Original Article(s)