• Saurabh Kumar Jha Department of Biotechnology, Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi -
  • Pravir Kumar Department of Biotechnology, Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi -



 Objective: Naringenin is a dietary biomolecule with broad spectrum of activities which protects neurons from various neurotoxic insults and improves cognition and motor function in neurodegenerative diseases. DJ-1 has both, ubiquitin E3 ligase as well as chaperonic activity, and loss of ubiquitin E3 ligase activity of DJ-1 has been found to be associated with familial Parkinson’s disease (PD). Naringenin induced E3 ligase activity of DJ-1 which can have possible clinical relevance in PD.

Methods: Various in silico parameters such as phylogenetic analysis, homology modeling, active site prediction, and molecular docking studies using AutoDock 4.2.1 and LIGPLOT1.4.5 were carried out.

Results: Three-dimensional structure of DJ-1 was generated and Ramachandran plot was obtained for quality assessment. RAMPAGE displayed 99.5% of residues in the most favored regions. 0% residues in additionally allowed and 0.5% disallowed regions of DJ-1 protein. Further, initial screenings of the molecules were done based on Lipinski’s rule of five. CastP server used to predict the ligand binding site suggests that this protein can be utilized as a potential drug target. Finally, we have found naringenin to be most effective among four biomolecules in modulating DJ-1 based on minimum inhibition constant, Ki, and highest negative free energy of binding with maximum interacting surface area in the course of docking studies.

Conclusion: Our study suggests that based on different in silico parameters and molecular docking studies, naringenin can provide a new avenue for PD therapeutics.

Keywords: Parkinson’s disease, Ubiquitin E3 ligase, DJ-1, Molecular docking, Naringenin.

Author Biographies

Saurabh Kumar Jha, Department of Biotechnology, Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi -

Molecular Neuroscience and Functional Genomics Laboratory,

Department of Biotechnology

PhD student

Pravir Kumar, Department of Biotechnology, Molecular Neuroscience and Functional Genomics Laboratory, Delhi Technological University (Formerly DCE), Delhi -

Associate Professor at Delhi Technological University (Former Delhi College of Engineering);

Ex-Faculty, Neurology Depaertment, Tufts University School of Medicine, Boston, MA USA


1. Massano J, Bhatia KP. Clinical approach to Parkinson’s disease: Features, diagnosis, and principles of management. Cold Spring Harb Perspect Med 2012;2(6):a008870.
2. Gundersen V. Protein aggregation in Parkinson’s disease. Acta Neurol Scand Suppl 2010;190:82-7.
3. Exner N, Lutz AK, Haass C, Winklhofer KF. Mitochondrial dysfunction in Parkinson’s disease: Molecular mechanisms and pathophysiological consequences. EMBO J 2012;31:3038-62.
4. Pirkevi C, Lesage S, Brice A, Basak AN. From genes to proteins in mendelian Parkinson’s disease: An overview. Anat Rec (Hoboken) 2009;292(12):1893-901.
5. Cookson MR. Parkinsonism due to mutations in PINK1, parkin, and DJ-1 and oxidative stress and mitochondrial pathways. Cold Spring Harb Perspect Med 2012;2(9):a009415.
6. Saurabh S, West AB. The therapeutic potential of LRRK2 and Α-synuclein in Parkinson’s disease. Antioxid Redox Signal 2009;11(9):2167-87.
7. Klein C, Westenberger A. Genetics of Parkinson’s disease. Cold Spring Harb Perspect Med 2012;2(1):a008888.
8. Saikat S, Chakraborty R, De B, Mazumder J. Free radicals, antioxidants, diseases and phytomedicines: Current status and future prospect. Indian J Pharm Sci 2010;3(1):91-100.
9. Jeremy PE. The interactions of flavonoids within neuronal signalling pathways. Genes Nutr 2007;2(3):257-73.
10. Jha SK, Jha NK, Kar R, Ambasta RK, Kumar P. p38 MAPK and PI3K/AKT signalling cascades in Parkinson’s disease. Int J Mol Cell Med 2015;4(2):67-86.
11. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 2010;4(8):118-26.
12. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool 1990;215(3):403-10.
13. Edgar RC. Muscle: A multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 2004;5:113.
14. Arnold K, Bordoli L, Kopp J, Schwede T. The SWISS-MODEL workspace: A web-based environment for protein structure homology modelling. Bioinformatics 2006;15;22:195-201.
15. Lipinski CA. Lead - And drug-like compounds: The rule-of-five revolution. Drug Discov Today Technol 2004;1(4):337-41.
16. Dundas J, Ouyang Z, Tseng J, Binkowski A, Turpaz Y, Liang J. CASTp: Computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues. Nucleic Acids Res 2006;34:116-8.
17. Wang C, Ma H, Feng X, Xie S, Chan P. Parkin dosage mutations in patients with early-onset sporadic and familial Parkinson’s disease in Chinese: An independent pathogenic role. Brain Res 2010;1358:30-8.
18. Mizuno Y, Fisher A, Hanin I. Progress in familial Parkinson’s disease. Parkinson’s Disease and Related Disorders. Vienna: Springer; 2006; p. 191-204.
19. Kumar GP, Khanum F. Neuroprotective potential of phytochemicals. Pharmacogn Rev 2012;6(12):81-90.
20. Azam F, Madi AM, Ali HI. Molecular docking and prediction of
pharmacokinetic properties of dual mechanism drugs that block MAO-B and adenosine A(2A) receptors for the treatment of Parkinson’s disease. J Young Pharm 2012;4(3):184-92.
21. Gupta P, Rai N, Gautam P. Anticancer drugs as potential inhibitors of acrab-tolc of multidrug resistant Escherichia coli: An in silico molecular modeling and docking study. Asian J Pharm Clin Res 2015;8(1):351-8.
22. Dharani RS, Ranjitha R, Sripathi R, Alimuhammad KS, Ravi S. Docking studies in target proteins involved in antibacterial actionmechanisms: Alkaloids isolated from Scutellaria genus. Asian J Pharm Clin Res 2016;9(5):121-5.
23. Engels M, Balaji BS, Divakar S, Geetha G. Ligand based pharmacophore modeling, virtual screening and molecular docking studies to design novel pancreatic lipase inhibitors. Int J Pharm Pharm Sci 2017;9(4):48-64.
24. Guerrero RV, Vargas RA, Petricevich VL. Chemical compounds and biological activity of an extract from Bougainvillea x Buttiana (var. Rose) holttum and standl. Int J Pharm Pharm Sci 2017;9(4):42-6.
25. Singh N, Kumar B, Kolli MK, Kumari M, Mishra AK. Molecular docking studies of some novel thiophene carbohydrazide derivatives on enterotoxin of bacillus cereus. Int J Curr Pharm Res 2016;8(3):59-63.
395 Views | 249 Downloads
How to Cite
Jha, S. K., and P. Kumar. “AN IN SILICO STUDY OF NARINGENIN-MEDIATED NEUROPROTECTION IN PARKINSON’S DISEASE”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 10, no. 8, Aug. 2017, pp. 171-6, doi:10.22159/ajpcr.2017.v10i8.18709.
Original Article(s)