Interaction of Cationic and Anionic Phthalocyanines with Adenosine Deaminase, Molecular Dynamics Simulation and Docking Studies


Interactions of anionic, cationic and metal phthalocyanine with adenosine deaminase were studied by molecular dynamics and docking simulation. Structural parameters such as solvent accessible surface area (SAS), mid-point of transition temperature (Tm), radial distribution function (RDF) and hydrogen bond, helix, coil, beta percentage and other physical parameters were obtained. The denaturation of adenosine deaminase (ADA) by heat, anionic and cationic phthalocyanines was compared. A series of 20 ns simulation performed at temperatures ranging from 275 to 450 K, starting from the ADA native structure. Results of radial distribution functions (RDFs) showed that metallic derivative at low concentration behaves the same as osmolytes that increases the beta form and increases the enzyme stability. Molecular docking studies have been carried out to confirm the simulation results. Investigation of binding site and free energy confirmed that the efficiency of interaction with adenosine deaminase depends on metal core. Binding energy of non-metallic form is more negative than metallic form and it significantly decreases for phthalocyanine. Self-aggregation of anionic phthalocyanine decreases in comparison with cationic derivative, therefore enzyme denaturation in the presence of anionic form is higher than the other. Furthermore, thermal stability of the enzyme also depends on temperature in presence of phthalocyanine. Binding site of phthalocyanine on the enzyme has been identified by docking analysis.

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D. Ajloo, S. Fazeli and F. Amirani, "Interaction of Cationic and Anionic Phthalocyanines with Adenosine Deaminase, Molecular Dynamics Simulation and Docking Studies," Computational Molecular Bioscience, Vol. 3 No. 4, 2013, pp. 81-93. doi: 10.4236/cmb.2013.34010.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] N. Spencer, D. Hopkinson and H. Harris, “Adenosine Deaminase Polymorphism in Man,” Annals of Human Genetics, Vol. 32, No. 1, 1968, pp. 9-14.
[2] P. E. Doddona, D. S. Schewach, E. N. Kelly, P. Argos, A. F. Markham and S. H. Orkin, “Human Adenosine Deaminase,” The Journal of Biological Chemistry, Vol. 259, No. 19, 1984, pp. 12101-12106.
[3] Z. Chang, P. Nygaard, A. C. Chinualt and R. E. Kellems, “Deduced Amino Acid Sequence of Escherichia coli Adenosine Deaminase Reveals Evolutionary Conserved Amino Acid Residues Implication for Catalytic Function,” Biochemistry, Vol. 30, No. 8, 1991, pp. 2273-2280.
[4] D. K. Wilson, F. B. Rudolph and F. A. Quiocho, “Atomic Structure of Adenosine Deaminase Complexed with a Transition-State Analog: Understanding Catalysis and Immunodeficiency Mutations,” Science, Vol. 252, No. 5010, 1991, pp. 1278-1284.
[5] G. K. Farber and G. A. Petsko, “The Evolution of Alpha/Beta Barrel Enzymes,” Trends in Biochemical Sciences, Vol. 15, No. 6, 1990, pp. 228-234.
[6] M. Hershfield, B. Mitchell, C. R. Scriver, A. L. Beaudet, W. Sly and D. Valle, “The Metabolic and Molecular Basis of Inherited Disease,” 17th Edition, McGraw-Hill, New York, 1995, pp. 1725-1768.
[7] M. van Der Weyden and W. Kelley, “Human Adenosine Deaminase. Distribution and Properties,” The Journal of Biological Chemistry, Vol. 251, No. 18, 1976, pp. 5448-5456.
[8] M. F. Baghanha, A. Pego and M. A. Lima, “Serum and Pleural Adenosine Deaminase Correlation with Lymphocyte Populations,” Chest, Vol. 97, No. 3, 1990, pp. 605-610.
[9] T. Hovi, J. F. Smyth, A. C. Allison and S. C. Williams, “Role of Adenosine Deaminase in Lymphocyte Proliferation,” Clinical & Experimental Immunology, Vol. 23, No. 3, 1976, pp. 395-403.
[10] J. L. Sullivan and R. J. Wedgewood, “Adenosine Deaminase Activity in Lymphocytes,” British Journal of Haematology, Vol. 37, No. 1, 1977, pp. 157-158.
[11] Y. Edwards, D. Hopkinson and H. Harris, “Adenosine Deaminase Isozymes in Human,” The Jornal Brasileiro de Pneumologia, Vol. 35, 1971, pp. 207-219.
[12] M. K. Bi, S. Klü, Y. Meri?, F. Ylmaz, O. Baar, G. Ylmaz, O. Yüksel, E. Yldrm and Z. Ztürk, “Serum Adenosine Deaminase Levels in Pancreatic Diseases,” Pancerat, Vol. 7, No. 5-6, 2007, pp. 5-6.
[13] M. Kaisemann, A. Kritski, M. Pereira and A. Trajman, “Pleural Fluid Adenosine Deaminase Detection for the Diagnosis of Pleural Tubercnlosis,” The Jornal Brasileiro de Pneumologia, Vol. 30, No. 6, 2004, pp. 549-556.
[14] S. Manjula, A. Raja, S. Rao, A. Aroor and A. Rao, “Serum Adenosine Deaminase Activity in Brain Tumours,” Acta Neurochirurgica, Vol. 121, No. 3-4, 1993, pp. 149-151.
[15] O. Z. Yildirim, H. Hasanoglu, O. Akyol, M. Gokirmak and N. Koksal, “Serum Adenosine Deaminase Activities in Lung Cancer and Mesothelioma,” Clinical Biochemistry, Vol. 32, No. 4, 1999, pp. 283-285.
[16] A. B. P. Lever, M. R. Hempstead, C. C. Leznoff, W. Lin, M. Melnik, W. A. Nevin and P. Seymour, “Recent Studies in Phthalocyanine Chemistry,” Pure and Applied Chemistry, Vol. 58, No. 11, 1986, pp. 1467-1476.
[17] E. Orti and J. L. Bredas, “Photoelectron Spectra of Phthalocyanine Thin Films: A Theoretical Interpretation,” Journal of the American Chemical Society, Vol. 114, No. 22, 1992, pp. 8669-8675.
[18] H. Ali and J. E. van Lier, “Porphyrins and Phthalocyanines as Photosensitizers and Radiosensitizers,” In: K. M. Kadish, K. M. Smith and R. Guilard, Eds., Handbook of Porphyrin Science with Applications to Chemistry, Physics, Materials Science, Engineering, Biology and Medecine, World Scientific: Singapore, 2010, pp. 1-119.
[19] A. Henriksson and M. Sundbom, “Semiempirical Molecular Orbital Studies of Phthalocyanines,” Theoretica Chimica Acta, Vol. 27, No. 3, 1972, pp. 213-222.
[20] A. K. Gosh, D. L. Morel, T. Feng and R. F. Shaw, “Three Dimensional Solar Cells Based on Optical Confinement Geometries,” Journal of Applied Physics, Vol. 45, 1974, pp. 230-236.
[21] A. Ghosh, P. G. Gassman and J. Almlof, “Substituent Effects in Porphyrazines and Phthalocyanines,” Journal of the American Chemical Society, Vol. 116, No. 5, 1994, pp. 1932-1940.
[22] R. D. Loutfy and J. H. Sharp, “Photovoltaic Properties of Metal-Free Phthalocyanines,” Journal of Chemical Physics, Vol. 71, No. 3, 1979, pp. 1211-1217.
[23] F. R. Fan and L. R. Faulkner, “Photovoltaic Effects of Metalfree and Zinc Phthalocyanines. I. Dark Electrical Properties of Rectifying Cells,” Journal of Chemical Physics, Vol. 69, No. 7, 1978, pp. 3334-3341.
[24] H. Jahnke, M. Schonborn and G. Zimmerman, “Synthesis and Characterization of ‘Face-to-Face’ Porphyrins,” Topics in Current Chemistry, Vol. 61, 1976, pp. 133-181.
[25] W. M. Sharmana, J. E van Liera and C. M. Allen, “Targeted Photodynamic Therapy by Receptor Mediated Delivery Systems,” Advanced Drug Delivery Reviews, Vol. 56, No. 1, 2004, pp. 53-76.
[26] Y. Y. Geng, D. H. Gu, Y. Q. Wu and F. X. Gan, “High Speed Recording Property of Phthalocyanine Thin Film for Compact Disc Recordable,” SPIE—The International Society for Optics and Photonics, Vol. 63, 2003, pp. 63-66.
[27] K. Petritsch, R. H. Friend, A. Lux, G. Rozenberg, S. C. Moratti and A. B. Holmes, “Liquid Crystalline Phthalocyanines in Organic Solar Cells,” Synthetic Metals, Vol. 102, No. 1-3, 1999, pp. 1776-1777.
[28] T. Nyokong and S. Vilakazi, “Phthalocyanines and Related Complexes as Electrocatalysts for the Detection of Nitric Oxide,” Talanta, Vol. 61, No. 1, 2003, pp. 27-35.
[29] M. Ethirajan, N. J. Patel and R. K. Pandey, “Porphyrin-Based Multifunctional Agents for Tumorimaging and Photodynamic Therapy (PDT),” In: K. M. Kadish, K. M. Smith and R. Guilard, Eds., Handbook of Porphyrin Science with Applications to Chemistry, Physics, Materials Science, Engineering, Biology and Medecine, World Scientific, Singapore. 2010, pp. 249-323.
[30] X. Yu, C. Z. Qing, Y. Y. Li and X. Z. Hong, “A Molecular Dynamics and Computational Study of Human KAT3 Involved in KYN Pathway,” Science China Chemistry, Vol. 56, No. 4, 2013, pp. 514-523.
[31] D. S. Zhao, Y. X. Chen and Q. Liu, “Exploring the Binding Mechanism of Thioflavin-T to the β-Amyloid Peptide by Blind Docking Method,” Science China Chemistry, Vol. 42, 2012, pp. 226-228.
[32] Y. X. Yu and S. Fujimoto, “Molecular Dynamics Simulation of the A-DNA to B-DNA Transition in Aqueous RbCl Solution,” Science China Chemistry, Vol. 56, No. 4, 2013, pp. 524-532.
[33] D. Ajloo, S. Hajipour, A. A. Saboury and S. Zakavi, “Effect of Cationic and Anionic Porphyrins on the Structure and Activity of Adenosine Deaminase,” Bulletin of the Korean Chemical Society, Vol. 32, No. 9, 2011, pp. 3411-3420.
[34] D. Ajloo, M. Sangian, M. Ghadamgahi, M. Evini and A. A. Sabouri, “Effect of Two Imidazolium Derivatives of Ionic Liquids on the Structure and Activity of Adenosine Deaminase,” International Journal of Biological Macromolecules, Vol. 55, 2013, pp. 47-61.
[35] M. Ghadamghahi, D. Ajloo and M. Moalem, “Kinetic Studies on the Self-Aggregation of a Non Ionic Porphyrin in the Presence and Absence of Ionic Liquid by Molecular Dynamics Simulation,” Journal of Porphyrins and Phthalocyanines, Vol. 16, No. 10, 2012, pp. 1082-1093.
[36] M. Ghadamghahi and D. Ajloo, “Calculation and Prediction of Rate and Equilibrium Constants for Aggregation of Porphyrin by Molecular Dynamics, Docking and QSPR,” Journal of Porphyrins and Phthalocyanines, Vol. 15, No. 4, 2011, pp. 240-256.
[37] E. van Der Spoel, B. Lindahl, G. Hess, A. E. Groenhof, H. J. Mark and H. J. C. Berendsen, “GROMACS: Fast, Flexible and Free,” Journal of Computational Chemistry, Vol. 26, No. 16, 2005, pp. 1701-1718.
[38] H. J. C. Berendsen, J. P. M. Postma, W. F. Hermans and J. van Gunsteren, In: B. Pullman, Ed., Intermolecular Forces, Dordecht, Holland, Reidel, 1981, 2005, pp. 331-342.
[39] L. Verlet, “Computer ‘Experiments’ on Classical Fluids. I. Thermodynamical Properties of Lennard-Jones Molecules,” Physical Review Letters, Vol. 159, 1967, pp. 98-103.
[40] T. A. Darden, D. York and L. G. Pedersen, “A Long-Range Electrostatic Potential Based on the Wolf Method Charge-Neutral Condition,” Chemical Physics, Vol. 98, No. 12, 1993, pp. 10089-10092.
[41] S. A. Nosé, “A Molecular Dynamics Method for Simulations in the Canonical Ensemble,” Molecular Physics, Vol. 52, No. 2, 1984, pp. 255-268.
[42] W. G. Hoover, “Canonical Dynamics: Equilibrium Phase-Space Distributions,” Physical Review Letters, Vol. 31, 1985, pp. 1695-1697.
[43] M. Parrinello and A. Rahman, “Crystal Structure and Pair Potentials: A Molecular-Dynamics Study,” Physical Review Letters, Vol. 45, No. 14, 1980, pp. 1196-1199.
[44] L. Ranjan, H. Zhang, H. Monzavi, R. F. Boyko, B. D. Sykes and D. S. Wishart, “VADAR: A Web Server for Quantitative Evaluation of Protein Structure Quality,” Nucleic Acids Research, Vol. 31, No. 13, 2003, pp. 3316-3319.

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