STABILITY OF OMEGA-3 COMPOUNDS COMPLEX WITH PPAR-γ RECEPTOR AS AN ANTI-OBESITY USING MOLECULAR DYNAMIC SIMULATION

Authors

  • IDA MUSFIROH Department of Pharmaceutical Analysis dan Medicinal Chemistry, Faculty of Pharmacy Universitas Padjadjaran Bandung Indonesia
  • GINNA MEGAWATI Division of Medical Nutrition, Department of Public Health, Faculty of Medicine Universitas Padjadjaran, Bandung, Indonesia, Doctoral Study Program, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
  • DEWI M. D. HERAWATI Division of Medical Nutrition, Department of Public Health, Faculty of Medicine Universitas Padjadjaran, Bandung, Indonesia
  • MUS IFAYA Department of Pharmaceutical Analysis dan Medicinal Chemistry, Faculty of Pharmacy Universitas Padjadjaran Bandung Indonesia, Department of Pharmacy, Faculty of Science and Technology, Universitas Mandala Waluya, Indonesia

DOI:

https://doi.org/10.22159/ijap.2022.v14s5.04

Keywords:

Molecular dynamic simulation, Obesity, Omega-3 fatty acids, PPAR-γ

Abstract

Objective: Obesity is a major contributor to comorbid diseases based on low grade chronic inflammation. Omega-3 fatty acids have a role in inflammation so it is thought to prevent obesity. This study was conducted to analyze the stability of omega-3 fatty acids with the PPAR-γ receptor using molecular dynamic simulation to investigate the relationship of macromolecule interactions to biologically relevant as an obesity comorbid.

Methods: The methods consisted of ligand acquisition, molecular dynamic simulation, and analysis of dynamic molecular results using Gromacs 2016.3 software and the results of the MD analysis were carried out by simulating time with VMD software and graphing the results of MD data analysis using Microsoft Excel.

Results: The result showed that docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and heneicosapentaenoic acid (HPA) have good stability. Average RMSD values of DHA, DPA, and HPA were 0.347 Å, 0.464 Å, and 0.706 Å with similar pattern of fluctuation across the region. DHA forms a hydrogen bond to Tyr347 and Leu343. Meanwhile, DPA binds to Asn52 and HPA bind to Arg213. DHA, DPA, and HPA have an average SASA of 233.91 nm2, 231.47 nm2, and 225.52 nm2, respectively. DHA has the lowest total binding energy (-129.914 kJ/mol) compared to DPA (-102.018 kJ/mol) and HPA (-115.992 kJ/mol).

Conclusion: Based on the molecular dynamics simulation approach, omega-3 compounds, DHA, DPA, and HPA showed that DHA has good stability compared to DPA and HPA. DHA, DPA, and HPA can be used as lead drugs to bind to PPAR-γ receptors to prevent and treat obesity.

Downloads

Download data is not yet available.

References

Fruh SM. Obesity: risk factors, complications, and strategies for sustainable long-term weight management. J Am Assoc Nurse Pract. 2017;29(S1)Suppl 1:S3-S14. doi: 10.1002/2327-6924.12510, PMID 29024553.

Calder PC. Very long chain omega-3 (n-3) fatty acids and human health. Eur J Lipid Sci Technol. 2014;116(10):1280-300. doi: 10.1002/ejlt.201400025.

Song T, Yang Y, Zhou Y, Wei H, Peng J. GPR120: a critical role in adipogenesis, inflammation, and energy metabolism in adipose tissue. Cell Mol Life Sci. 2017;74(15):2723-33. doi: 10.1007/s00018-017-2492-2, PMID 28285320.

Chandra M, Miriyala S, Panchatcharam M. PPARγ and its role in cardiovascular diseases. PPAR Res. 2017;2017:6404638. doi: 10.1155/2017/6404638, PMID 28243251.

Brogi S, Ramalho TC, Kuca K, Medina Franco JL, Valko M. Editorial: in silico methods for drug design and discovery. Front Chem. 2020;8(612):612. doi: 10.3389/fchem.2020.00612, PMID 32850641.

Megawati G, Herawati DMD, Musfiroh I. Binding affinity of omega-3 fatty acid as an agonist PPAR-γ and GPR120 receptor for obesity using molecular docking and ADME prediction. Eur J Mol Clin Med. 2021;710:1686-95.

Musfiroh I, Megawati G, Herawati DMD, Rusdin A. 3D-pharmacophore modelling of omega-3 derivatives with peroxisome proliferator-activated receptor gamma as an anti-obesity agent. Int J App Pharm. 2021;13(4):167-70. doi: 10.22159/ijap.2021.v13s4.43851.

Hospital A, Goni JR, Orozco M, Gelpi JL. Molecular dynamics simulations: advances and applications. Adv Appl Bioinform Chem. 2015;8(8):37-47. doi: 10.2147/AABC.S70333, PMID 26604800.

Case D, Babin J, Berryman J. Amber reference manual. San Francisco: University of California; 2014.

Zhao Y, Zeng C, Massiah MA. Molecular dynamics simulation reveals insights into the mechanism of unfolding by the A130T/V mutations within the MID1 zinc-binding Bbox1 domain. Plos One. 2015;10(4):e0124377. doi: 10.1371/journal.pone.0124377, PMID 25874572.

Zaki AA, Ashour A, Elhady SS, Darwish KM, Al-Karmalawy AA. Calendulaglycoside a showing potential activity against SARS-CoV-2 main protease: molecular docking, molecular dynamics, and SAR studies. J Tradit Complement Med. 2022;12(1):16-34. doi: 10.1016/j.jtcme.2021.05.001, PMID 34026584.

Fenwick S, Vanga SK, DiNardo A, Wang J, Raghavan V, Singh A. Computational evaluation of the effect of processing on the trypsin and alpha‐amylase inhibitor from Ragi (Eleusine coracana) seed. Eng Rep. 2019;1(4):(e212064). doi: 10.1002/eng2.12064.

Kitao A. Principal component analysis and related methods for investigating the dynamics of biological macromolecules. Journal. 2022;5(2):298-317. doi: 10.3390/j5020021.

Pitaloka DAE, Ramadhan DSF, Arfan CL, Chaidir L, Fakih TM. Docking-based virtual screening and molecular dynamics simulations of quercetin analogs as enoyl-acyl carrier protein reductase (InhA) inhibitors of Mycobacterium tuberculosis. Sci Pharm. 2021;89(2):1-11. doi: 10.3390/scipharm89020020.

Kumari R, Kumar R, Open Source Drug Discovery Consortium, Lynn A. G_mmpbsa-a GROMACS tool for high-throughput MM-PBSA calculations. J Chem Inf Model. 2014;54(7):1951-62. doi: 10.1021/ci500020m. PMID 24850022.

Published

27-12-2022

How to Cite

MUSFIROH, I., MEGAWATI, G., HERAWATI, D. M. D., & IFAYA, M. (2022). STABILITY OF OMEGA-3 COMPOUNDS COMPLEX WITH PPAR-γ RECEPTOR AS AN ANTI-OBESITY USING MOLECULAR DYNAMIC SIMULATION. International Journal of Applied Pharmaceutics, 14(5), 45–49. https://doi.org/10.22159/ijap.2022.v14s5.04

Issue

Section

Original Article(s)