Molecular Docking and Molecular Dynamics Studies of L-Glycyl-L-Glutamic Acid Dipeptide

Yıl 2019, Cilt: 3 Sayı: 1, 1 - 9, 30.03.2019

Bilge Bıçak , Serda Kecel Gündüz , Yağmur Kökcü Ayşen E. Özel Sevim Akyüz

https://doi.org/10.30516/bilgesci.476841

Cited By: 14

Öz

The Gly-Glu (GE) dipeptide, which
acts as a neurotransmitter, is made of glycine and glutamic amino acids that
are used in the treatment of neurological diseases such as Schizophrenia,
Parkinson and Alzheimer. Gly-Glu dipeptide is an important peptide structure
that helps prevent neuronal degeneration, especially in Alzeimer's disease.
Caspases which are cysteine proteases play a crucial role for apoptotic death
of neurons in Alzheimer’s disease. In patients with Alzheimer's disease, there
was an increase in caspase-3 immunoreactivity in the death of pyramidal
neurons, where the initial sites of neuronal loss were proven (Gervais et al.
1999). The molecular structure of the GE dipeptide having anti-apoptotic
properties is very important for clarifying the activation mechanism with
caspase-3 protein. Molecular dynamics and molecular docking calculations were
applied to elucidate the most stable molecular conformation and to grasp the
mechanism of activity of GE with caspase-3. Firstly, GROMACS program was used
to reveal the conformation variations of the GE within the body. The stability
of the peptide is ensured by confinement in 704 water molecules. Secondly,
Glide SP (standard precision) module of the Maestro 11.4 version in the
Schrodinger Software program was used to determine the linkages and activity of
the peptide with the caspase-3 protein. In this study, the structure of this
dipeptide, pharmacological properties and its mechanism of action with
caspase-3 protein were investigated for the first time by molecular dynamics
and docking calculations.

Anahtar Kelimeler

Gly-Glu, dipeptide, Molecular Dynamics, Molecular Docking, ADME

Kaynakça

• Aprison, M. H., & Werman, R. (1965). The distribution of glycine in cat spinal cord and roots. Life sciences, 4(21), 2075.
• Becker, J. W., Rotonda, J., Soisson, S. M., Aspiotis, R., Bayly, C., Francoeur, S., ... & Han, Y. (2004). Reducing the peptidyl features of caspase-3 inhibitors: a structural analysis. Journal of medicinal chemistry, 47(10), 2466-2474.
• Benet, L. Z., Kroetz, D., Sheiner, L., Hardman, J., & Limbird, L. (1996). Pharmacokinetics: the dynamics of drug absorption, distribution, metabolism, and elimination. Goodman and Gilman’s the pharmacological basis of therapeutics, 3-27.
• Berendsen, H. J. C. (1991). Transport properties computed by linear response through weak coupling to a bath. In: Computer Simulations in Material Science.
• Bienert, S., Waterhouse, A., de Beer, T. A., Tauriello, G., Studer, G., Bordoli, L., & Schwede, T. (2016). The SWISS-MODEL Repository—new features and functionality. Nucleic acids research, 45(D1), D313-D319.
• Bosshard, H. R., Marti, D. N., & Jelesarov, I. (2004). Protein stabilization by salt bridges: concepts, experimental approaches and clarification of some misunderstandings. Journal of Molecular Recognition, 17(1), 1-16.
• Brandon, C., & Lam, D. M. (1983). L-glutamic acid: a neurotransmitter candidate for cone photoreceptors in human and rat retinas. Proceedings of the National Academy of Sciences, 80(16), 5117-5121.
• Brecht, S., Gelderblom, M., Srinivasan, A., Mielke, K., Dityateva, G., & Herdegen, T. (2001). Caspase-3 activation and DNA fragmentation in primary hippocampal neurons following glutamate excitotoxicity. Molecular Brain Research, 94(1-2), 25-34.
• Butina, D., Segall, M. D., & Frankcombe, K. (2002). Predicting ADME properties in silico: methods and models. Drug discovery today, 7(11), S83-S88.
• Ferreira, L. G., dos Santos, R. N., Oliva, G., & Andricopulo, A. D. (2015). Molecular docking and structure-based drug design strategies. Molecules, 20(7), 13384-13421.
• Friesner, R. A., Murphy, R. B., Repasky, M. P., Frye, L. L., Greenwood, J. R., Halgren, T. A., ... & Mainz, D. T. (2006). Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein− ligand complexes. Journal of medicinal chemistry, 49(21), 6177-6196.
• Friesner, R. A., Banks, J. L., Murphy, R. B., Halgren, T. A., Klicic, J. J., Mainz, D. T., ... & Shaw, D. E. (2004). Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. Journal of medicinal chemistry, 47(7), 1739-1749.
• Frisch, M. J. E. A., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., ... & Nakatsuji, H. (2009). Gaussian 09, revision a. 02, gaussian. Inc., Wallingford, CT, 200.
• Gervais, F. G., Xu, D., Robertson, G. S., Vaillancourt, J. P., Zhu, Y., Huang, J., ... & Clarke, E. E. (1999). Involvement of caspases in proteolytic cleavage of Alzheimer’s amyloid-β precursor protein and amyloidogenic Aβ peptide formation. Cell, 97(3), 395-406.
• Halgren, T. A., Murphy, R. B., Friesner, R. A., Beard, H. S., Frye, L. L., Pollard, W. T., & Banks, J. L. (2004). Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. Journal of medicinal chemistry, 47(7), 1750-1759.
• Harder, E., Damm, W., Maple, J., Wu, C., Reboul, M., Xiang, J. Y., ... & Kaus, J. W. (2015). OPLS3: a force field providing broad coverage of drug-like small molecules and proteins. Journal of chemical theory and computation, 12(1), 281-296.
• Hess, B., Bekker, H., Berendsen, H. J., & Fraaije, J. G. (1997). LINCS: a linear constraint solver for molecular simulations. Journal of computational chemistry, 18(12), 1463-1472.
• Huang, S. Y., & Zou, X. (2010). Advances and challenges in protein-ligand docking. International journal of molecular sciences, 11(8), 3016-3034.
• Ioudina, M., & Uemura, E. (2003). A three amino acid peptide, Gly-Pro-Arg, protects and rescues cell death induced by amyloid β-peptide. Experimental neurology, 184(2), 923-929.
• Koelle, G. B., Sanville, U. J., & Wall, S. J. (1985). Glycyl-L-glutamine, a precursor, and glycyl-L-glutamic acid, a neurotrophic factor for maintenance of acetylcholinesterase and butyrylcholinesterase in the preganglionically denervated superior cervical ganglion of the cat in vivo. Proceedings of the National Academy of Sciences, 82(15), 5213-5217.
• Lexa, K. W., Dolghih, E., & Jacobson, M. P. (2014). A structure-based model for predicting serum albumin binding. PLoS One, 9(4), e93323.
• Li, C. (2002). Poly (L-glutamic acid)–anticancer drug conjugates. Advanced drug delivery reviews, 54(5), 695-713.
• Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced drug delivery reviews, 23(1-3), 3-25.
• Lipinski, C. A. (2004). Lead-and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies, 1(4), 337-341.
• Manto, M. U., Laute, M. A., Aguera, M., Rogemond, V., Pandolfo, M., & Honnorat, J. (2007). Effects of anti–glutamic acid decarboxylase antibodies associated with neurological diseases. Annals of neurology, 61(6), 544-551.
• McDermott Jr, W. V., Wareham, J., & Riddell, A. G. (1955). Treatment of hepatic coma with L-glutamic acid. New England Journal of Medicine, 253(25), 1093-1102.
• Parrinello, M., & Rahman, A. (1981). Polymorphic transitions in single crystals: A new molecular dynamics method. Journal of Applied physics, 52(12), 7182-7190.
• Sastry, G. M., Adzhigirey, M., Day, T., Annabhimoju, R., & Sherman, W. (2013). Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. Journal of computer-aided molecular design, 27(3), 221-234.
• Shahidi, F. (Ed.). (1997). Natural antioxidants: chemistry, health effects, and applications. The American Oil Chemists Society.
• Smith, P. E., & van Gunsteren, W. F. (1993). The viscosity of SPC and SPC/E water at 277 and 300 K. Chemical physics letters, 215(4), 315-318.
• Søndergaard, C. R., Olsson, M. H., Rostkowski, M., & Jensen, J. H. (2011). Improved treatment of ligands and coupling effects in empirical calculation and rationalization of p K a values. Journal of chemical theory and computation, 7(7), 2284-2295.
• Turner, P. J. (2005). XMGRACE, Version 5.1. 19. Center for Coastal and Land-Margin Research, Oregon Graduate Institute of Science and Technology, Beaverton, OR.
• Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E., & Berendsen, H. J. (2005). GROMACS: fast, flexible, and free. Journal of computational chemistry, 26(16), 1701-1718.
• van Gunsteren, W. F., & Berendsen, H. J. (1987). Groningen molecular simulation (GROMOS) library manual. Biomos, Groningen, 24(682704), 13.
• Venkatesan, A., Rambabu, M., Jayanthi, S., & Febin Prabhu Dass, J. (2018). Pharmacophore feature prediction and molecular docking approach to identify novel anti‐HCV protease inhibitors. Journal of cellular biochemistry, 119(1), 960-966.
• Zhong, Z., Wheeler, M. D., Li, X., Froh, M., Schemmer, P., Yin, M., ... & Lemasters, J. J. (2003). L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Current Opinion in Clinical Nutrition & Metabolic Care, 6(2), 229-240.