Volume : 7, Issue : 8, AUG 2021

GAMMA-D-CRYSTALLIN EYE LENS PROTEIN IS TARGETED FOR SENILE CATARACT- AN IN SILICO ANALYSIS

KIRUBA RAJAMANI, R. SATHISH KUMAR*

Abstract

Age-related or senile cataract is one of the important reasons for blindness in half of the world. Opacification of the inner core region of the lens that focuses the light on the retina is inevitable with aging. Gamma-D-crystallin protein is present in the middle layer of the lens, which undergoes biochemical and physiological changes leading to opacification of the lens. The primary treatment of senile cataract includes surgery, but surgical treatment is not accessible by most people, so identification of anti-cataract drugs to treat cataract is focused in the present study. The main objective of the present study is to predict the tentative binding parameters like ligand chemistry, receptor flexibility and the scoring function of ligand-receptor complex and predominant binding mode (s) of a ligand with the target protein - Gamma-D-crystallin. Drug compounds are retrieved from the PubChem database. The 3D structure of Gamma-D-crystallin protein was retrieved from the PDB ID 2G98. Drug compounds are screened primarily for ADMETox properties, and docking studies were performed using Glide module of Schrodinger software. Docking studies of 3D model of Gamma-D-crystallin protein with  ligands revealed that most of them have good binding affinity and maximum G score. In particular, the drug compound salsalate showed -9.21 Kcal/mol of G.score and formed 3 numbers of hydrogen bonds with the residues Arg79,Gln54. It is found to have prominent interactions.

Keywords

SENILE CATARACT, GAMMA CRYSTALLIN PROTEIN, EYE LENS PROTEIN, IN SILICO ANALYSIS, DOCKING STUDIES.

Article : Download PDF

Cite This Article

Article No : 4

Number of Downloads : 440

References

  1. Moncef Khairallah, Rim Kahloun, Rupert Bourne, Hans Limburg, Seth R. Flaxman, Jost B. Jonas, Jill Keeffe, Janet Leasher, Kovin Naidoo, Konrad Pesudovs, Holly Price, Richard A. White, Tien Y. Wong, Serge Resnikoff, Hugh R. Taylor. (2015) Vision Loss Expert Group of the Global Burden of Disease Study Investigative, Ophthalmology & Visual Science October. Vol.56, 6762-6769.
  2. Yasemin Budama-Kilinc, Rabia Cakir-Koc, Serda Kecel-Gunduz, Yagmur Kokcu, Bilge Bicak, Hande Mutlu, Aysen E. (2018) Novel NAC-loaded poly (lactide-co-glycolide acid) nanoparticles for cataract treatment: preparation, characterization, evaluation of structure, cytotoxicity, and molecular docking studies. PeerJ 6:e4270.
  3. Pascolini D & Mariotti SP. (2012) Global estimates of visual impairment. Br J Ophthalmol. 96: 614–618.
  4. Hamdy Abdelkader, Raid G. Alanyac and Barbara Pierscionek. (2015) Age-related cataract and drug

 

therapy: opportunities and challenges for topical antioxidant delivery to the lens, Journal of Pharmacy and Pharmacology. Volume 67, Issue 4, Pages 537–550

  1. Vinson JA. (2006) Oxidative stress in cataracts. Pathophysiology 13, 151–162.
  2. Rosenthal R. (2002) Outcome indicators for cataract. In: Rosenthal R, ed. Health Outcome Indicators. London: University of Oxford. 1–86
  3. Bloemendal H, de Jong W, Jaenicke R, Lubsen NH, Slingsby C, Tardieu A. (2004) Ageing and vision: structure, stability and function of lens crystallins. Prog Biophys Mol Biol.86: 407–485.
  4. Liu XF, Hao JL, Xie T, Malik TH, Lu CB, Liu C, Shu C, Lu CW, Zhou DD. (2017) Nrf2 as a target for the prevention of age-related and diabetic cataracts by against oxidative stress. Aging Cell. 16, 934–942.
  5. Harding J. (1991) The ageing lens. In: Harding J, ed. Cataract: Biochemistry, Epidemiology and Pharmacology. London: Chapman and Hall. 71–81.
  6. Wilmarth P, et al. (2006) Age-related changes in human crystallins determined from comparative analysis of post-translational modifications in young and aged lens: does deamidation contribute to crystallin insolubility? J Proteome Res. 5: 2554–2566.
  7. Higashide T, Sugiyama K. (2008) Use of viscoelastic substance in ophthalmic surgery - focus on sodium hyaluronate. Clin Ophthalmol 2(1):21-30.
  8. Duan P, Liu Y, Li J. (2017) The comparative efficacy and safety of topical non-steroidal anti-inflammatory drugs for the treatment of anterior chamber inflammation after cataract surgery: a systematic review and network meta-analysis. Graefes Arch Clin Exp Ophthalmol 255(4):639–649.
  9. Dick HB, Schwenn O, Krummenauer F, Krist R, Pfeiffer N. (2000) Inflammation after sclerocorneal versus clear corneal tunnel phacoemulsification. Ophthalmology. 107(2):241–247
  10. Yasemin Budama-Kilinc, Rabia Cakir-Koc, Serda Kecel-Gunduz, Yagmur Kokcu, Bilge Bicak, Hande Mutlu, Aysen E. (2018) Novel NAC-loaded poly (lactide-co-glycolide acid) nanoparticles for cataract treatment: preparation, characterization, evaluation of structure, cytotoxicity, and molecular docking studies. PeerJ 6:e4270.
  11. Shen H, et al. (2010) Synthesis and biological evaluations of novel bendazac lysine analogues as potent anticataractagents. Bioorg Med Chem Lett. 20: 2115–2118.
  12. Testa M, et al. (1987) Higher efficacy of flunoxaprofen over bendazac and other non-steroidal anti-inflammatory drugs in treatment of cataract. CurrTherap Res 42: 182–189.
  13. Maggs JL, Park BK. (1988) Drug-protein conjugates XVI studies of sorbinil metabolism: formation of 2- hydroxysorbinil and unstable protein conjugates. BiochemPharmacol. 37: 743–748
  14. Tauseef M, et al. (2008) Antioxidative action of aspirin on endothelial function in hypercholesterolaemic rats. Basic Clin Pharmacol Toxicol. 103: 314–321
  15. Abdelkader H, et al. (2011) New therapeutic approaches in treatment of diabetic keratopathy. Clin Exp Opthalmol. 39: 259–270.
  16. Pang YP & Kozikowski AP. (1994) Prediction of the binding sites of huperzine A in acetylcholinesterase by docking studies. Journal of Computer-Aided Molecular Design 8(6), 669–681.
  17. Sampark S Thakkar, Parth Thakor, Hiren Doshi, Arabinda Ray. (2017) 1,2,4-Triazole and 1,3,4-oxadiazole analogues: Synthesis, MO studies, in silico molecular docking studies, antimalarial as DHFR inhibitor and antimicrobial activities. Bioorganic & Medicinal Chemistry 25 4064–4075
  18. Muhammad S & Fatima N. (2015) In silico analysis and molecular docking studies of potential angiotensin-converting enzyme inhibitor using quercetin glycosides. Pharmacognosy Magazine 11(42), 123.
  19. Alves, Ferreira, Froufe, Abreu, Martins, Pintado. (2013) Antimicrobial activity of phenolic compounds identified in wild mushrooms, SAR analysis and docking studies. Journal of Applied Microbiology 115, 346-35.