Conformational Analysis of Tyrosyl-Lysyl-Threonine Tripeptide Using MM, MD and QM Methods and Its Hyperpolarizability Study

Year 2022, , 745 - 756, 31.08.2022

Bilge Bıçak , Serda Kecel Gunduz

https://doi.org/10.16984/saufenbilder.1025541

Abstract

Peptides are important structures that offer important opportunities for therapeutic interventions in various diseases. Tyrosyl-Lysyl-Threonine is an important peptide structure that contains the antiviral, antioxidant and anticancer properties of the amino acids in its structure. Examination of the conformational structure, which has great importance on both the ability of the molecule to fulfill its biological functions and electronic properties, is important for molecular studies. In this study, determination of the stable conformations and optimization of the most stable structure of Tyrosyl-Lysyl-Threonine molecule was carried out using molecular mechanical and quantum mechanical methods. With molecular dynamics simulation studies, the changes in conformational structure, RMSD and Rg values in different environments were monitored for 10 ns. Additionally, the hyperpolarizability study of Tyrosyl-Lysyl-Threonine were carried out. As a result of this study, it was aimed to determine the optimized geometry of the tripeptide, its conformational changes and nonlinear optical properties.

Keywords

peptide, conformational analysis, hyperpolarizability

Supporting Institution

İstanbul Üniversitesi

Project Number

FDK-2018-32253

Thanks

We thank Prof Dr Petra Imhof and her team for their advice on MD studies.

References

• [1] D. Agyei, I. Ahmed, Z. Akram, M. N. Iqbal, H., M. K. Danquah, “Protein and peptide biopharmaceuticals: an overview,” Protein and peptide letters, vol. 24, no. 2, pp. 94-101, 2017.
• [2] D. Agyei, M. K. Danquah, “Industrial-scale manufacturing of pharmaceutical-grade bioactive peptides,” Biotechnology Advances, vol. 29, no. 3, pp. 272-277, 2011.
• [3] K. Fosgerau, T. Hoffmann, “Peptide therapeutics: current status and future directions,” Drug Discovery Today, vol. 20, no. 1, pp. 122-128, 2015.
• [4] R. E. Hancock, H. G. Sahl, “Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies,” Nature Biotechnology, vol. 24, no. 12, pp. 1551-1557, 2006.
• [5] S. S. Usmani, G. Bedi, J. S. Samuel, S. Singh, S. Kalra, P. Kumar, ... & G. P. Raghava, “THPdb: Database of FDA-approved peptide and protein therapeutics,” PloS one, vol. 12, no. 7, e0181748, 2017.
• [6] H. R. Lieberman, S. Corkin, B. J. Spring, R. J. Wurtman, J. H. Growdon, “The effects of dietary neurotransmitter precursors on human behavior,” The American Journal of Clinical Nutrition, vol. 42, no. 2, pp. 366-370, 1985.
• [7] D. D. Rasmussen, B. Ishizuka, M. E. Quigley, S. S. C. Yen, “Effects of tyrosine and tryptophan ingestion on plasma catecholamine and 3, 4-dihydroxyphenylacetic acid concentrations,” The Journal of Clinical Endocrinology & Metabolism, vol. 57, no. 4, pp. 760-763, 1983.
• [8] I. Gülçin, “Comparison of in vitro antioxidant and antiradical activities of L-tyrosine and L-Dopa,” Amino Acids, vol. 32, no. 3, pp. 431, 2007.
• [9] H. M. Chen, K. Muramoto, F. Yamauchi, K. Nokihara, “Antioxidant activity of designed peptides based on the antioxidative peptide isolated from digests of a soybean protein.” Journal of Agricultural and Food Chemistry, vol. 44, no. 9, pp. 2619-2623, 1996.
• [10] R. W. Tankersley, “Amino acid requirements of herpes simplex virus in human cells,” Journal of bacteriology, vol. 87, no. 3, pp. 609-613, 1964.
• [11] N. A. El‐Sersy, A. E. Abdelwahab, S. S. Abouelkhiir, D. M. Abou‐Zeid, S. A. Sabry, “Antibacterial and Anticancer activity of ε‐poly‐L‐lysine (ε‐PL) produced by a marine Bacillus subtilis sp.,” Journal of basic microbiology, vol. 52, no. 5, pp. 513-522, 2012.
• [12] P. Simic, H. Sahm, L. Eggeling, “L-Threonine export: use of peptides to identify a new translocator from Corynebacterium glutamicum,” Journal of bacteriology, vol. 183, no. 18, pp. 5317-5324, 2001.
• [13] P. Li, Y. L. Yin, D. Li, S. W. Kim, G. Wu, “Amino acids and immune function,” British Journal of Nutrition, vol. 98, no. 2, pp. 237-252, 2007.
• [14] R. F. Bertolo, C. Z. Chen, G. Law, P. B. Pencharz, R. O. Ball, “Threonine requirement of neonatal piglets receiving total parenteral nutrition is considerably lower than that of piglets receiving an identical diet intragastrically,” The Journal of nutrition, vol. 128, no. 10, pp. 1752-1759, 1998.
• [15] W. W. Wang, S. Y. Qiao, D. F. Li, “Amino acids and gut function,” Amino acids, vol. 37, no. 1, pp. 105-110, 2009.
• [16] K. A. Bala, M. Dogan, T. Mutluer, S. Kaba, O. Aslan, R. Balahoroglu, ... & S. Kocaman, “Plasma amino acid profile in autism spectrum disorder (ASD),” Eur Rev Med Pharmacol Sci, vol. 20, no. 5, pp. 923-929, 2016.
• [17] P. Chen, N. Bodor, W. M. Wu, L. Prokai, “Strategies to target kyotorphin analogues to the brain,” Journal of medicinal chemistry, vol. 41, no. 20, pp. 3773-3781, 1998.
• [18] B. N. P. Sah, T. Vasiljevic, S. Mckechnie, O. N. Donkor, “Identification of anticancer peptides from bovine milk proteins and their potential roles in management of cancer: a critical review,” Comprehensive Reviews in Food Science and Food Safety, vol. 14, no. 2, pp. 123-138, 2015.
• [19] H. Otani, H. Suzuki, “Isolation and characterization of cytotoxic small peptides, α‐casecidins, from bovine αs1‐casein digested with bovine trypsin,” Animal Science Journal, vol. 74, no. 5, pp. 427-435, 2003.
• [20] B. Bicak, S. Kecel Gunduz, Y. Budama Kilinc, P. Imhof, B. Gok, G. Akman, A. E. Ozel, “Structural, spectroscopic, in silico, in vitro and DNA binding evaluations of tyrosyl-lysyl-threonine,” Journal of Biomolecular Structure and Dynamics, 1-17, 2021.
• [21] B. Bicak, Y. Budama Kilinc, S. Kecel Gunduz, T. Zorlud, G. Akman, “Peptide based nano-drug candidate for cancer treatment: Preparation, characterization, in vitro and in silico evaluation,” Journal of Molecular Structure, 1240, 130573, 2021.
• [22] B. Bicak, S. Kecel Gunduz, Y. Budama Kilinc, B. Ozdemir, “Molecular docking studies of YKT tripeptide and drug delivery system with poly (ε‐caprolactone) nanoparticles,” Archiv der Pharmazie, e2100437, 2022.
• [23] I. S. Maksumov, L. I. Ismailova, N. M. Godzhaev, “A program for the semiempirical calculation of the conformations of molecular complexes on a computer,” Journal of structural chemistry, vol. 24, no. 4, pp. 647-648, 1984.
• [24] C. M. Venkatachalam, G. N. Ramachandran, “Conformation of polypeptide chains,” Annual review of biochemistry, vol. 38, no. 1, pp. 45-82, 1969.
• [25] G. T. Ramachandran, V. Sasisekharan, “Conformation of polypeptides and proteins,” Advances in protein chemistry, vol. 23, pp. 283-437, 1968.
• [26] G. Friesecke, F. Theil, “Molecular geometry optimization, models,” Encyclopedia of Applied and Computational Mathematics, pp. 951-957, 2015.
• [27] A. Janaki, V. Balachandran, A. Lakshmi, “First order molecular hyperpolarizabilities and intramolecular charge transfer from vibrational spectra of NLO material: 2, 6-dichloro-4-nitroaniline,” vol. 51, no. 09, pp. 601-614, 2013.
• [28] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, ... & D. J. Fox, Gaussian 09; Gaussian, Inc. Wallingford, CT, vol. 32, pp. 5648-5652, 2009.
• [29] W. F. van Gunsteren, S. R. Billeter, A. A. Eising, P. H. Hünenberger, P. K. H. C. Krüger, A. E. Mark, ... & I. G. Tironi, “Biomolecular simulation: the GROMOS96 manual and user guide,” Vdf Hochschulverlag AG an der ETH Zürich, Zürich, vol. 86, pp. 1-1044, 1996.
• [30] D. Van Der Spoel, E. Lindahl, B. Hess, G. Groenhof, A. E. Mark, H. J. Berendsen, “GROMACS: fast, flexible, and free,” Journal of computational chemistry, vol. 26, no. 16, pp. 1701-1718, 2005.
• [31] G. Bussi, D. Donadio, M. Parrinello, “Canonical sampling through velocity rescaling,” The Journal of chemical physics, vol. 126, no. 1, pp. 014101, 2007.
• [32] M. Parrinello, A. Rahman, “Polymorphic transitions in single crystals: A new molecular dynamics method,” Journal of Applied physics, 52(12), 7182-7190, 1981.
• [33] P. J. Turner, “XMGRACE, Version 5.1. 19.” Center for Coastal and Land-Margin Research, Oregon Graduate Institute of Science and Technology, Beaverton, OR. 2005.
• [34] W. Humphrey, A. Dalke, K. Schulten, “VMD: visual molecular Dynamics,” Journal of molecular graphics, vol. 14, no. 1, pp. 33-38, 1996.
• [35] D. van der Spoel, “Structure and dynamics of peptides: theoretical aspects of protein folding,” Doctoral Thesis, 1996.
• [36] Y. X. Sun, , Q. L. Hao, , W. X. Wei, , Z. X. Yu, , L. D. Lu, X. Wang, Y. S. Wang, “Experimental and density functional studies on 4-(3, 4-dihydroxybenzylideneamino) antipyrine, and 4-(2, 3, 4-trihydroxybenzylideneamino) antipyrine,” Journal of Molecular Structure: THEOCHEM, vol. 904, no. 1-3, pp. 74-82, 2009.
• [37] E. V. Shah, D. R. Roy, “A comparative DFT study on electronic, thermodynamic and optical properties of telluride compounds,” Computational materials science, vol. 88, pp. 156-162, 2014.
• [38] S. Kecel-Gunduz, B. Bicak, S. Celik, S. Akyuz, A. E. Ozel, “Structural and spectroscopic investigation on antioxidant dipeptide, l-Methionyl-l-Serine: A combined experimental and DFT study,” Journal of Molecular Structure, vol. 1137, pp. 756-770, 2017.