In silico docking studies of RP2 (X-Linked retinitis pigmentosa) protein using anthocyanins as potential inhibitors
DOI:
https://doi.org/10.3329/bjp.v8i3.15110Keywords:
Anthocyanins, Cyanidin 3, 5 Diglucoside, Flavonoids, Syzygium cumini,Abstract
Mutations occurring in X-Linked retinitis pigmentosa (RP2) gene causes retinal damage, ultimately leading to vision loss. Owing to the complications of the disease, there is no effective treatment till date. In the present study, we have refined the crystal structure of RP2 using protein preparation wizard of Glide software. Active site of the protein was predicted with SiteMap program. Five anthocyanin compounds from Syzygium cumini fruit peel were docked into the active site of RP2. Molecular docking calculations were performed by employing Glide XP algorithm. Cyanidin 3,5 diglucoside with lowest Gscore (-12.62 kcal/mol) was rescored subsequently with Prime-MMGBSA binding free energy calculations. Binding affinity (-93.62 kcal/mol) of the inhibitor suggests its potential use in the treatment of retinitis pigmentosa.
Downloads
305
266 Read
11
References
Adisakwattana S, Yibchok-Anun S, Charoenlertkul P, Wongsasiripat N. Cyanidin-3-rutinoside alleviates postprandial hyperglycemia and its synergism with acarbose by inhibition of intestinal α-glucosidase. J Clin Biochem Nutr. 2011; 49: 36-41.
Ayuso C, Jose MM. Retinitis pigmentosa and allied conditions today: a paradigm of translational research. Genome Med. 2010; 2: 34.
Berson EL, Rosner B, Sandberg MA, Weigel-Difranco C, Willett WC. ?-3 intake and visual acuity in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2012; 130: 707-11.
Bhalla S, Joshi D, Bhullar S, Kasuga D, Park Y, Kay CN. Long-term follow-up for efficacy and safety of treatment of retinitis pigmentosa with valproic acid. Br J Ophthalmol. 2013.
Byamukama R, Kiremire BT, Andersen OM, Steigen A. Anthocyanins from fruits of Rubus Pinnatus and Rubus Rigidus. J Food Composit Anal. 2005; 18: 599-605.
DiMasi JA, Hansen RW, Grabowski HG. The price of innovation: New estimates of drug development costs. J Health Econ. 2003; 22: 151-85.
Eldridge MD, Murray CW, Auton TR, Paolini GV, Mee RP. Empirical scoring functions: the development of a fast empirical scoring function to estimate the binding affinity of ligands in receptor complexes. J Comput-Aided Mol Des. 1997; 11:425-45.
Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, Sanschagrin PC, Mainz DT. Extra precision Glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem. 2006; 49: 6177-96.
Ghosh D, Konishi T. Anthocyanins and anthocyanin-rich extracts: role in diabetes and eye function. Asia Pac J Clin Nutr. 2007; 16: 200-08.
Glide, version 5.8, Schrödinger, LLC, New York, NY, 2012.
Halgren TA. Identifying and characterizing binding sites and assessing druggability. J Chem Inf Model. 2009; 49: 377-89.
Hardcastle AJ, Thiselton DL, Van Maldergem L, Saha BK, Jay M, Plant C, Taylor R, Bird AC, Bhattacharya S. Mutations in the RP2 gene cause disease in 10% families with familial X-Linked retinitis pigmentosa in this study. Am J Hum Genet. 1999; 64: 1210-15.
Inglehearn CF. Molecular genetics of human retinal dystrophies. Eye 1998; 12: 571-79.
Jeong JW, Lee WS, Shin SC, Kim G-Y, Choi BT, Choi YH. Anthocyanins Downregulate Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglial Cells by Suppressing the NF-κB and Akt/MAPKs Signaling Pathways. Int J Mol Sci. 2013; 14: 1502-15.
Ji HF, Li XJ, Zhang HY. Natural products and drug discovery can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia? Embo Reports. 2009; 10: 194-200.
Kong JM, Chia LS, Goh NK, Chia TF, Brouillard R. Analysis and biological activities of anthocyanins. Phytochemistry 2003; 64: 923-33.
Kuhnel K, Veltel S, Schlichting I, Wittinghofer A. Crystal structure of the human retinitis pigmentosa 2 protein and its interaction with Arl3. Structure 2006; 14: 367-78.
Lee J, Lee HK, Kim CY, Hong YJ, Choe CM, You TW, Seong GJ. Purified high-dose anthocyanoside oligomer administration improves nocturnal vision and clinical symptoms in myopia subjects. Br J Nutr. 2005; 93: 895-99.
Li T, Sandberg MA, Pawlyk BS, Rosner B, Hayes KC, Dryja TP, Berson EL. Effect of vitamin A supplementation on rhodopsin mutants threonine-17?methionine and proline-347 ?serine in transgenic mice and in cell cultures. Proc Natl Acad Sci U S A. 1998; 95: 11933-38.
LigPrep, version 2.5, Schrödinger, LLC, New York, NY, 2012.
Maestro, version 9.3, Schrödinger, LLC, New York, NY, 2012.
Matsumoto H, Inaba H, Kishi M, Tominaga S, Hirayama M, Tsuda T. Orally administered delphinidin 3-rutinoside and cyanidin 3-rutinoside are directly absorbed in rats and humans and appear in the blood as the intact forms. J Agric Food Chem. 2001; 49: 1546-51.
Matsunaga N, Imai S, Inokuchi Y, Shimazawa M, Yokata S, Araki Y, Hara H. Bilberry and its main constituents have neuroprotective effects against retinal neuronal damage in vitro and in vivo. Mol Nutr Food Res. 2009; 53: 869-77.
Miyake S, Takahashi N, Sasaki M, Kobayashi S, Tsubota K, Ozawa Y. Vision preservation during retinal inflammation by anthocyanin-rich bilberry extract: cellualr and molecular mechanism. Lab Invest. 2012; 92: 102-09.
Nakaishi H, Matsumoto H, Tominaga S, Hirayama M. Effects of black currant anthocyanoside intake on dark adaptation and VDT work-induced transient refractive alteration in healthy humans. Altern Med Rev. 2000; 5: 553-62.
Pearlman, DA. Evaluating the molecular mechanics Poisson-Boltzmann surface area free energy method using a congeneric series of ligands to p38 MAP kinase. J.Med.Chem. 2005; 48: 7796-807.
Prime, version 3.1, Schrödinger, LLC, New York, NY, 2012.
Priya SSL, Devi RP, Eganathan P, Nishith ST. Structure prediction of Bestrophin for the induced-fit docking of anthocyanins, Bioinformation 2012; 8: 742-48.
Rundquist, J. Low vision rehabilitation of retinitis pigmentosa. J Vis Impair Blind. 2004; 98: 718-24.
Sandberg MA, Rosner B, Weigel-DiFranco C, Berson EL. Lack of scientific rationale for use of valproic acid for retinitis pigmentosa. Br J Ophthalmol. 2011; 95: 744.
Scharrer A, Ober M. Anthocyanosides in the treatment of retinopathies. Klin Monatsbl Augenheilkd 1981; 178: 386-89.
Szajdek A, Borowska EJ. Bioactive compounds and health-promoting properties of berry fruits: A review. Plant Foods Hum Nutr. 2008; 63: 147-56.
Taylor CW. Anthocyanins in cardiovascular diseases. Adv Nutr. 2011; 2: 1-7.
Tiupula KC, Blaem F, Yanamala N, Klein-Seetharaman J. pH- dependent interaction of rhodopsin with cyanidin-3-glucoside. 2. Functional aspects. Photochem Photobiol. 2009; 85: 463-70.
Veigas JM, Narayan MS, Laxman PM, Neelwarne B. Chemical nature, stability and bioefficacies of anthocyanins from fruit peel of Syzygium cumini Skeels. Food Chem. 2007; 105: 619-27.
Veltel S, Wittinghofer A. RPGR and RP2: targets for the treatment of X-linked retinitis pigmentosa? Expert Opin Ther Targets. 2009; 13: 1239-51.
Wang LS, Stoner GD. Anthocyanins and their role in cancer prevention. Cancer Lett. 2008; 269: 281-90.
Wrolstad RE. Interaction of natural colors with other ingredients. J Food Sci. 2004; 69: 419-21.
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
