Uji In Silico Reaktivitas Reseptor NMDA (N-Metil-D-Aspartat) Ensefalitis terhadap Hidroksiprolin
Abstract
Abstract. Encephalitis is an inflammation of the brain caused by parenchymal virus infection. There is another cause of encephalitis which is caused by autoimmune. NMDA receptors are receptors responsible for encephalitis. Hydroxyproline is an amino acid resulting from modification of the amino acid proline. So, hydroxyproline becomes an important metabolite in immunulogical encephalitis at the NMDA receptor. The purpose of this study was to study safety based on the activity between hydroxrolin composition of NMDA receptors in silico compared to their natural ligands. In this study a trial was carried out on NMDA silico encephalitis reactivity receptors against hydroxyproline using a protein-ligand based molecular inhibition method. NMDA receptors and natural ligands are taken first. The best reform simulation was chosen for docking simulation of NMDA receptors. Based on the results of the research, it shows that hydroxyproline compounds have a low risk of security to NMDA receptors because of the docking results obtained free energy bond (∆G) of -4.91 Kcal/mol, compared to natural ligand (d-serine) of -6.35 Kcal/mol. It is predicted that the affinity of hydroxyproline bonds to the receptor is very strong and has a low risk of security, supported by the parameters of the cramer rule is the High (Class III) category.
Keywords: Encephalitis, Hydoxyproline, NMDA receptor
Abstrak. Ensefalitis adalah inflamasi pada parenkim otak yang disebabkan oleh infeksi virus. Terdapat penyebab ensefalitis lain yaitu disebakan oleh autoimun. Reseptor NMDA adalah reseptor yang bertanggung jawab terhadap ensefalitis. Hidroksiprolin adalah asam amino hasil dari modifikasi asam amino prolin, sehingga hidroksiprolin merupakan metabolit yang penting dalam ensefalitis imunulogi pada reseptor NMDA. Tujuan dari penelitian ini adalah untuk melakukan study keamanan berdasarkan aktivitas antara senyawa hidrosiprolin terhadap reseptor NMDA secara in silico yang dibandingkan dengan ligan alaminya. Dalam penelitian ini dilakukan uji in silico reaktivitas reseptor NMDA ensefalitis terhadap hidroksiprolin menggunakan motode penambatan molekular berbasis ligan-protein. Reseptor NMDA dan ligan alami dipisahkan terlebih dahulu. Konformasi senyawa uji terbaik dipilih untuk dilakukan simulasi docking terhadap reseptor NMDA. Berdarkan hasil penelitian, menunjukan senyawa hidroksiprolin memiliki resiko keamaanan yang rendah terhadap reseptor NMDA karena dari hasil docking didapat energi bebas ikatan (∆G) sebesar -4,91 Kcal/mol, dibanding ligan alami (d-serine) sebesar -6.35 Kcal/mol. Diprediksi afinitas ikatan hidroksiprolin terhadap reseptor sangat kuat dan memiliki resiko keamaanan yang rendah, didukung dengan parameter cramer rules masuk kategori High (Class III).
Kata Kunci: Ensefalitis, Hidroksiprolin, Reseptor NMDA
Keywords
Full Text:
PDFReferences
Bustillos, R.J.A., C.W. Olsen., D.A. Olson, B. Chiou, E. Yee, P.J. Bechtel and T.H. McHugh. (2006). Water vapor permeability of mammalian and fish gelatin films. Journal of Food Science, 4(71):202-207.
Dalmau J, Lancaster E, Hernandez EM, Rosenfeld MR, dan Gordon RB. (2011). Clinical Experience and Laboratory Investigations In Patients With Anti-NMDAR Encephalitis. Lancet Neurol. 10(1): 63-74.
Ferdinand P dan Mitchell L. (2012). Anti-NMDA Receptor Encephalitis. J Clin Cell Immunol. S10:1-6.
Fischer, E. (1902). Gelatin Manufacturers Institute of America.USA. 35:2660-2665.
Gleichman AJ, Spruce LA, Dalmau J, Seeholzer SH, dan Lynch DR. (2012). Anti-NMDA Receptor Encephalitis Antibody Binding is Dependent on Amino Acid Identity of a Small Region within the GluN1 Amino Terminal Domain. The Journal of Neuroscience. 32(32): 11082-11094.
Jones KC, Benseler SM, dan Moharir M. (2013). Anti-NMDA Receptor Encephalitis. Neuroimag Clin N Am. 23: 309-320.
Kartasasmita, Emran, Rahmana., Herowati, Rina., Harmastuti, Nuraeni., Gusdiar, Tutus. (2009). Quercetin Derivatives Docking Based on Study Of Flavonoids Interaction To Cyclooxygenase-2. Indo. J. Chem, 9 (2): 297- 302.
Kelly, L., Gorres, Ronald, T., Raines. (2010). Review Artikel Prolyl 4-hydroxylase. USA. University of Wisconsin Madison.
Kesuma, D., Siswandono., Bambang, T. P., Suko, H. (2018). Uji in silico Aktivitas Sitotoksik Senyawa Turunan N-(Benzoil)-N’-fenilteourea sebagai Calon Obat Antikanker. J Pharm Sci Clin Res. 01:2.
Kontoyianni, M., McClellan, L.M., Sokol, G.S. (2004). Evaluation of docking performance: comparative data on docking algorithm. Journal of Medicinal Chemistry, 47:558- 565.
Lenox BR, Coles AJ, dan Vincent A. (2012). Antibody-mediated encephalitis: a treatable cause of schizophrenia. BJPsych. 200: 92-94.
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. (1997). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 23, 3-25.
Longo D, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J. (2011). Harrison’s Principles of Internal Medicine: Volumes 1 and 2, 18th Edition. McGraw-Hill Professional.
Luca N, Daengsuwan T, Dalmau J, Jones K, deVeber G, Kobayashi J, Laxer RM, dan Benseler SM. (2011). Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Newly Recognized Inflammatory Brain Disease in Children. Arthritis Rheum. 63(8): 2516-2522.
Motiejunas, D., & Wade, R. (2006). Structural, Energetics, and Dynamic Aspects of Ligand-Receptor Interactions. In J. B. Taylor & D. J. Triggle (Eds.), Comprehensive Medicinal Chemistry II Volume 4: Computer-Assisted Drug Design (Vol. 4, pp. 193-214). Elsevier.
Peery HE, Day GS, Dunn S., et al. (2012 March). Anti-NMDA receptor encephalitis. The disorder, the diagnosis and the immunobiology, Autoimmun; AUTREV-01245; No of Pages 10
Sikorski, E. Dorian N. Scott, David H. Buisson &R. Malcolm Love. (2009). The role of collagen in the quality and processing of fish. C R C Critical Reviews in Food Science and Nutrition, Vol 20
Suhud, Farida. (2015). Uji Aktivitas in silico Senyawa Baru 1-Benzil-3-benzoilurea Induk dan Tersubstitusi sebagai Agen Antirolifratif. Jurnal Farmasi Indonesia. 7:243.
DOI: http://dx.doi.org/10.29313/.v6i2.24029
