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Abstract

Arginine, useful in protein refolding, solubilization of proteins, and suppression of protein aggregation and non-specific adsorption during formulation and purification, is a ubiquitous additive in the biotechnology and pharmaceutical industries. In order to provide a framework for analyzing the molecular level mechanisms behind arginine/protein interactions in the above context, density functional theory was used to systematically examine how arginine interacts with naturally occurring amino acids. The results show that the most favorable interaction of arginine is with acidic amino acids and arises from charge interactions and hydrogen-bond interactions. Arginine is also shown to form stacking and T-shaped structures with aromatic amino acids, the types of cation–p and N–H…p interactions, respectively, known to be important contributors to protein stability. The analysis also shows that arginine-arginine interactions lead to stable clusters, with the stability of the clusters arising from the stacking of the guanidinium part of arginine. The results show that the unique ability of arginine to form clusters with itself makes it an effective aggregation suppressant and support the interpretations of the current study using experimental and molecular dynamics results available in the literature. The results also contribute to understanding the role of arginine in increasing protein solubility, imparting thermal stability of important enzymes, and designing better additives.

 

 

Keywords

Protein aggregation Protein solubility Arginine Quantum chemical calculation Amino acid.

Article Details

How to Cite
Shaikh, A. R., & Shah, D. (2015). Arginine-Amino Acid Interactions and Implications to Protein Solubility and Aggregation. The Journal of Engineering Research [TJER], 12(2), 1–14. https://doi.org/10.24200/tjer.vol12iss2pp1-14
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References

  1. Andzelm J, Govind N, Fitzgerald G, Maiti A (2003), DFT study of methanol conversion to hydrocarbons in a zeolite catalyst. International Journal of Quantum Chemistry 91(3): 467-473.
  2. Arakawa T, Ejima D, Tsumoto K, Obeyama N, Tanaka Y, Kita Y, Timasheff SN (2007), Suppression of protein interactions by arginine: a proposed mechanism of the arginine effects. Biophysical Chemistry 127(1-2): 1-8.
  3. Cellamare S, Stefanachi A, Stolfa DA, Basile T, Catto M, Campagna F, Sotelo E, Acquafredda P, Carotti A (2008), Design, synthesis, and biological evaluation of glycine-based molecular tongs as inhibitors of Aβ1–40 aggregation in vitro. Bioorganic and Medicinal Chemistry 16: 4810-4822.
  4. Chakarova-Kack SD, Schroder E, Lundqvist BI, Langreth DC (2006), Application of van der Waals density functional to an extended system: adsorption of benzene and naphthalene on graphite. Physical Review Letter 96(14): 46107-(1-4).
  5. Chen D, Martin ZS, Soto C, Schein CH (2009), Computational selection of inhibitors of Abeta aggregation and neuronal toxicity. Bioorganic and Medicinal Chemistry 17: 5189-5197.
  6. Cleland JL (1991), Mechanisms protein aggregation and refolding. PhD Thesis, Massachusetts Institute of Technology, Cambridge.
  7. Das U, Hariprasad G, Ethayathulla AS, Manral P, Das TK, Pasha S, Mann A, Ganguli M, Verma AK, Bhat R, Chandrayan SK, Ahmed S, Sharma S, Kaur P, Singh TP, Srinivasan A (2007), Inhibition of protein aggregation: supramolecular assemblies of arginine hold the key. PLoS One 2(11): e1176.
  8. Delley B (1990), An all-electron numerical method for solving the local density functional for polyatomic molecules. Journal of Chemical Physics 92(1): 508-517.
  9. Delley B (2000), From molecules to solids with the DMol3 approach. Journal of Chemical Physics 113(18): 7756-7764.
  10. Ejima D, Yumioka R, Arakawa T, Tsumoto K (2005), Arginine as an effective additive in gel permeation chromatography. Journal of Chromatography A 1094(1-2): 49-55.
  11. Flocco MM, Mowbray SL (1994), Planar stacking interactions of arginine and aromatic side chains in proteins. Journal of Molecular Biology 235: 709- 717.
  12. Frokjaer S, Otzen DE (2005), Protein drug stability: a formulation challenge. Nature Review Drug Discovery 4: 298-306.
  13. Ghosh R, Sharma S, Chattopadhyay, K (2009), Effect of arginine on protein aggregation studied by fluorescence correlation spectroscopy and other biophysical methods. Biochemistry 48(5): 1135-1143.
  14. Gregoret LM, Rader SD, Fletterick RJ, Cohen FE (1991), Hydrogen bonds involving sulfur atoms in proteins. Proteins Structure Function Genetics 9: 99-107.
  15. Iwaoka M, Takemoto S, Okada M, Tomoda S (2002), Weak nonbonded S•••X (X = O, N, and S) interactions in proteins. Statistical and Theoretical Studies. Bulletin of Chemical Society of Japan 75: 1611-1625.
  16. Ito L, Shiraki K, Matsuura T, Okumura M, Hasegawa K, Baba S, Yamaguchi H, Kumasaka T (2011), High-resolution X-ray analysis reveals binding of arginine to aromatic residues of lysozyme surface: implication of suppression of protein aggregation by arginine. Protein Engineering Design and Selection 24(3): 269-74.
  17. Julian RR, Hodyss R, Beauchamp JL (2001), Salt bridge stabilization of charged zwitterionic arginine aggregates in the gas phase. Journal of American Chemical Society 123: 3577-3583.
  18. Klamt A (1995), Conductor-like screening model for real solvents: A New Approach to the Quantitative Calculation of Solvation Phenomena. Journal of Physical Chemistry 99(7): 2224-2235.
  19. Klamt A, Schuurmann G (1993), COSMO: a new approach to dielectric screening in solvents with explicit expressions for the screening energy and its gradient. Journal of Chemical Society Perkin Transaction 2(5): 799-805.
  20. Lee SH, Carpenter JF, Chang BS, Randolph TW, Kim YS (2006), Effects of solutes on solubilization and refolding of proteins from inclusion bodies with high hydrostatic pressure. Protein Science 15: 304-313.
  21. Leippert M, Beck E, Weiland F, Pfaff E (1997), Point mutations within the betaG-betaH loop of footand- mouth disease virus O1K affect virus attachment to target cells. Journal of Virology 71: 1046-1051.
  22. Lim WK, Rosgen J, Englander SW (2009), Urea, but not guanidinium, destabilizes proteins by forming hydrogen bonds to the peptide group. Proceedings of Natural Academy of Sciences USA 106(8): 2595-2600.
  23. Martis RL, Singh SK, Gromiha MM, Santhosh C (2008), Role of cation-pi interactions in single chain 'all-alpha' proteins. Journal of Theoretical Biology 250: 655-662.
  24. Matsuoka T, Tomita S, Hamada H, Shiraki K (2007), Amidated amino acids are prominent additives for preventing heat-induced aggregation of lysozyme. Journal of Bioscience and Bioengineering 103(5): 440-443.
  25. Melo A, Ramos MJ, Floriano WB, Gomes JANF, Leão JFR, Magalhães AL, Maigret B, Nascimento MC, Reuter N (1999), Theoretical study of arginine-carboxylate interactions. Journal of Molecular Structure THEOCHEM 463(1-2): 81-90.
  26. Natsume T, Ishikawa Y, Dedachi K, Tsukamoto T, Kurita N (2006), DFT study of the electronic properties of DNA–DNA and PNA–DNA double strands. International Journal of Quantum Chemistry 106(15): 3278-3287.
  27. Ortmann F, Schmidt WG, Bechstedt F (2005), Attracted by long-range electron correlation: adenine on graphite. Physical Review Letter 95(18): 186101-(1-4).
  28. Ottiger P, Pfaffen C, Leist R, Leutwyler S, Bachorz RA, Klopper W (2009), Strong N-H...pi hydrogen bonding in amide-benzene interactions. Journal of Physical Chemistry B 113: 2937-2943.
  29. Ryu S, Park TG (1998), Thermal stabilization of aspergillus phytase by L-arginine. Biotechnology Bioprocess Engineering 3(1): 32-34.
  30. Shah D, Shaikh AR, Peng X, Rajagopalan R (2011), Effects of arginine of heat-induced aggregation of concentrated protein solutions. Biotechnology Progress 27(2): 513-520.
  31. Shah D, Li J, Shaikh AR, Rajagopalan R (2012), Arginine–aromatic interactions and their effects on arginine-induced solubilization of aromatic solutes and suppression of protein aggregation. Biotechnology Progress 28(1): 223-231.
  32. Shiraki K, Kudou M, Fujiwara S, Imanaka T, Takagi M (2002), Biophysical effect of amino acids on the prevention of protein aggregation. The Journal of Biochemistry 132: 591-595.
  33. Takano K, Higashi R, Okada J, Mukaiyama A, Tadokoro T, Koga Y, Kanaya S (2009), Proline effect on the thermostability and slow unfolding of a hyperthermophilic protein. The Journal of Biochemistry 145(1): 79-85.
  34. Timasheff SN (2002), Protein hydration, thermodynamic binding, and preferential hydration. Biochemistry 41(46): 13473-13482.
  35. Vondrasek J, Mason PE, Heyda J, Collins KD, Jungwirth P (2009), The molecular origin of likecharge arginine-arginine pairing in water. Journal of Physical Chemistry B 113: 9041-9045.