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Quantum Chemical Approaches in Modeling the Structure of DNA Quadruplexes and Their Interaction with Metal Ions and Small Molecules

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Application of Computational Techniques in Pharmacy and Medicine

Part of the book series: Challenges and Advances in Computational Chemistry and Physics ((COCH,volume 17))

Abstract

Certain guanine-rich DNA and RNA sequences can fold into unique biologically significant high-order structures called G-quadruplexes (G4) formed by stacked arrays of guanine quartets connected by non-canonical hydrogen bonds. Novel anticancer strategy is based on the use of organic molecules that specifically target quadruplex structures present in telomeres and some other regions of the genome. We provide a brief overview of the structural features of quadruplex nucleic acids and main mechanisms of G4-ligand interaction. Current methods for the molecular modeling of quadruplex DNA structures and their ligand binding are discussed in the review. We mainly focus on quantum chemical computational approaches to model the interaction of G4 DNA and its structural elements with metal cations and small molecules, including hybrid QM/MM approaches.

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REFERENCES

  1. Harley CB (2008) Telomerase and cancer therapeutics. Nature Rev. Cancer 8:167–179.

    CAS  Google Scholar 

  2. Rudolph KL (2010) Telomeres and Telomerase in Aging, Disease, and Cancer. Springer-Verlag, Berlin-Heidelberg

    Google Scholar 

  3. Tian X, Chen B, Liu X (2010) Telomere and telomerase as targets for cancer therapy. Appl Biochem Biotechnol 160:1460–1472

    CAS  Google Scholar 

  4. Ruden M, Puri N (2012) Novel anticancer therapeutics targeting telomerase. Cancer Treat Rev doi:10.1016/j.ctrv.2012.06.007

    Google Scholar 

  5. De Cian A, Lacroix L, Douarre C, Temime-Smaali N, Trentesaux C, Riou J-F, Mergny J-L (2008) Targeting telomeres and telomerase. Biochimie 90:131–155

    CAS  Google Scholar 

  6. Tarkanyi I, Aradi J (2008) Pharmacological intervention strategies for affecting telomerase activity. Further prospects to treat cancer and degenerative diseases. Biochimie 90:156–172

    CAS  Google Scholar 

  7. Xu Y (2011) Chemistry in human telomere biology: structure, function and targeting of telomere DNA/RNA. Chem Soc Rev 40:2719–2740

    CAS  Google Scholar 

  8. Andrews L, Tollefsbol TO. (eds) (2011) Telomerase Inhibition: Strategies and Protocols. Humana Press, New York.

    Google Scholar 

  9. Chen H, Li Y, Tollefsbol TO. (2009) Strategies targeting telomerase inhibition. Mol Biotechnol 41:194–199

    CAS  Google Scholar 

  10. Neidle S (2010) Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer. FEBS J. 277:1118–1125

    CAS  Google Scholar 

  11. Collie G.W, Parkinson GN (2011) The application of DNA and RNA G-quadruplexes to therapeutic medicines. Chem Soc Rev 40:5867–5892.

    CAS  Google Scholar 

  12. Kaushik M, Kaushik S, Bansal A, Saxena S, Kukreti S. (2011) Structural diversity and specific recognition of four stranded G-quadruplex DNA. Curr Mol Med 11:744–769

    CAS  Google Scholar 

  13. Duchler M (2012) G-quadruplexes: targets and tools in anticancer drug design. J Drug Target 20:389–400

    CAS  Google Scholar 

  14. Huppert JL, Balasubramanian S (2007) G-quadruplexes in promoters throughout the human genome. Nucleic Acids Res. 35:406–413

    CAS  Google Scholar 

  15. Balasubramanian S, Hurley LH, Neidle S (2011) Targeting G-quadruplexes in gene promoters: a novel anticancer strategy?. Nature Rev Drug Discov 10:261–275

    CAS  Google Scholar 

  16. Ji X, Sun H, Zhou H, Xiang J, Tang Y, Zhao C (2011) Research progress of RNA quadruplex. Nucleic Acid Ther 21:185–200

    CAS  Google Scholar 

  17. Millevoi S, Moine H, Vagner S (2012) G-quadruplexes in RNA biology. Wiley Interdisc. Rev RNA 3:495–507

    CAS  Google Scholar 

  18. Xu Y, Komiyama M (2012) Structure, function and targeting of human telomere RNA. Methods 57:100–105

    CAS  Google Scholar 

  19. Hardin CC, Perry AG, White K (2001) Thermodynamic and kinetic characterization of the dissociation and assembly of quadruplex nucleic acids. Biopolym 56:147–194

    CAS  Google Scholar 

  20. Kumar N, Maiti S (2005) The effect of osmolytes and small molecule on Quadruplex-WC duplex equilibrium: a fluorescence resonance energy transfer study. Nucleic Acids Res 33:6723–6732.

    CAS  Google Scholar 

  21. Monchaud D., Teulade-Fichou M.-P. (2008). A hitchhiker’s guide to G-quadruplex ligands. Org Biomol Chem 6:627–636

    CAS  Google Scholar 

  22. Le TVT, Han S, Chae J, Park H-J (2012). G-quadruplex binding ligands: from naturally occurring to rationally designed molecules Curr Pharm Des 18:1948–1972

    CAS  Google Scholar 

  23. Paul A, Bhattacharya S (2012) Chemistry and biology of DNA-binding small molecules. Curr Sci 102:212–231

    CAS  Google Scholar 

  24. Gonzalez-Ruiz V, Olives AI, Martin MA, Ribelles P, Ramos MT, Menendez JC (2011) An overview of analytical techniques employed to evidence drug-DNA interactions. Applications to the design of genosensors. In: Olsztynska S. (ed.). Biomedical engineering. trends, research and technologies. InTech, Rijeka, p. 65–90

    Google Scholar 

  25. Murat P, Singh Y, Defrancq E (2011) Methods for investigating G-quadruplex DNA/ligand interactions. Chem Soc Rev 40:5293–307

    CAS  Google Scholar 

  26. Palchaudhuri R, Hergenrother PJ (2007) DNA as a target for anticancer compounds: methods to determine the mode of binding and the mechanism of action. Curr Opin Biotechnol 18:497–503

    CAS  Google Scholar 

  27. Sun D, Hurley H (2010) Biochemical techniques for the characterization of G-quadruplex structures: EMSA, DMS footprinting and DNA polymerase stop assay. Methods Mol Biol 608:65–79

    CAS  Google Scholar 

  28. Mergny J-L, Lacroix L (2009) UV melting of G-quadruplexes. Curr Protoc Nucleic Acid Chem 37:17.1.1–17.1.15. doi: 10.1002/0471142700.nc1701s37

    Google Scholar 

  29. Olsen CM, Marky LA (2010) Monitoring the temperature unfolding of G-quadruplexes by UV and circular dichroism spectroscopies and calorimetry techniques. Methods Mol Biol 608:147–158

    CAS  Google Scholar 

  30. Vorlíčková M, Kejnovská I, Sagi J, Renčiuk D, Bednářová K, Motlová J, Kypr J (2012) Circular dichroism and guanine quadruplexes. Methods 57:64–75

    Google Scholar 

  31. Juskowiak B, Takenaka S (2006) Fluorescence resonance energy transfer in the studies of guanine quadruplexes. Methods Mol Biol. 335:311–341

    CAS  Google Scholar 

  32. Okumus B, Ha T (2010) Real-time observation of G-quadruplex dynamics using single-molecule FRET microscopy. Methods Mol Biol 608: 81–96

    CAS  Google Scholar 

  33. De Cian A, Guittat L, Kaiser M, Saccà B, Amrane S, Bourdoncle A, Alberti P, Teulade-Fichou M-P, Lacroix L, Mergny J-L (2007) Fluorescence-based melting assays for studying quadruplex ligands. Methods 42:183–195

    CAS  Google Scholar 

  34. Zhao Y, Kan Z-y, Zeng Z-x, Hao Y-h, Chen H, Tan Z (2004) Determining the folding and unfolding rate constants of nucleic acids by biosensor. application to telomere G-quadruplex. J Am Chem Soc 126:13255–13264

    CAS  Google Scholar 

  35. Redman JE (2007) Surface plasmon resonance for probing quadruplex folding and interactions with proteins and small molecules. Methods 43:302–312

    CAS  Google Scholar 

  36. Schlachter C, Lisdat F, Frohme M, Erdmann VA, Konthur Z, Lehrach H, Glökler J (2012) Pushing the detection limits: The evanescent field in surface plasmon resonance and analyte-induced folding observation of long human telomeric repeats. Biosens. Bioelectron 31:571–574

    CAS  Google Scholar 

  37. Parkinson GN, Lee MP, Neidle S (2002) Crystal structure of parallel quadruplexes from human telomeric DNA. Nature 417:876–880

    CAS  Google Scholar 

  38. Li J, Correia JJ, Wang L, Trent JO, Chaires JB (2005) Not so crystal clear: the structure of the human telomere G-quadruplex in solution differs from that present in a crystal. Nucleic Acids Res 33:4649–4659

    CAS  Google Scholar 

  39. Campbell NH, Parkinson GN (2007) Crystallographic studies of quadruplex nucleic acids. Methods 43:252–263

    CAS  Google Scholar 

  40. Neidle S, Parkinson GN (2008) Quadruplex DNA crystal structures and drug design. Biochimie 90:1184–1196

    CAS  Google Scholar 

  41. Campbell N, Collie GW, Neidle S (2012) Crystallography of DNA and RNA G-quadruplex nucleic acids and their ligand complexes. Curr Protoc Nucleic Acid Chem 50:17.6.1–17.6.22. doi: 10.1002/0471142700.nc1706s50

    Google Scholar 

  42. Webba da Silva M (2007) NMR methods for studying quadruplex nucleic acids. Methods 43:264–277

    Google Scholar 

  43. Adrian M, Heddi B, Phan AT (2012) NMR spectroscopy of G-quadruplexes. Methods 57:11–24

    CAS  Google Scholar 

  44. Hehre JW, Radom L, Schleyer P, Pople J (1986) Ab initio molecular orbital theory. John Wiley and Sons, New York

    Google Scholar 

  45. Berkert U, Allinger NL (1982) Molecular Mechanics. American Chem Soc Washington, DC

    Google Scholar 

  46. Tsai SC (2007) Biomacromolecules. Introduction to Structure, Function and Informatics. Wiley-Liss, New York p. 249–288

    Google Scholar 

  47. Šponer J, Šponer JE, Mládek A, Jurečka P, Banáš P, Otyepka M (2013) Nature and magnitude of aromatic base stacking in DNA and RNA: Quantum chemistry, molecular mechanics, and experiment. Biopolym, 99, 978–988.

    Google Scholar 

  48. McCammon JA, Harvey SC (1987) Dynamics of Proteins and Nucleic Acids. Cambridge University Press, New York

    Google Scholar 

  49. Špačková N, Berger I, Šponer J (2001) Structural dynamics and cation interactions of DNA quadruplex molecules containing mixed guanine/cytosine quartets revealed by large-scale MD simulations. J Am Chem Soc 123:3295–3307

    Google Scholar 

  50. Šponer J, Špačková N (2007) Molecular dynamics simulations and their application to four-stranded DNA. Methods 43:278–290

    Google Scholar 

  51. Haider S, Parkinson GN, Neidle S (2008) Molecular dynamics and principal components analysis of human telomeric quadruplex multimers. Biophys J 95:296–311

    CAS  Google Scholar 

  52. Šponer J, Cang X, Cheatham TE III (2012) Molecular dynamics simulations of G-DNA and perspectives on the simulation of nucleic acid structures. Methods 57:25–39

    Google Scholar 

  53. Chowdhury S, Bansal M (2000) Effect of coordinated ions on structure and flexibility of parallel G-quandruplexes: a molecular dynamics study. J Biomol Struct Dyn 18:11–28

    CAS  Google Scholar 

  54. Cavallari M, Calzolari A, Garbesi A., DiFelice R (2006) Stability and migration of metal ions in G4-wires by molecular dynamics simulations. J Phys Chem B 110:26337–26348

    CAS  Google Scholar 

  55. Akhshi P, Acton G, Wu G (2012) Molecular dynamics simulations to provide new insights into the asymmetrical ammonium ion movement inside of the [d(G3T4G4)]2 G-quadruplex DNA structure. J Phys Chem B 116:9363–9370

    CAS  Google Scholar 

  56. Novotny J, Kulhanek P, Marek R (2012) Biocompatible xanthine-quadruplex scaffold for ion-transporting DNA channels. J Phys Chem Lett 3:1788–1792

    CAS  Google Scholar 

  57. Read MA, Wood AA, Harrison JR, Gowan SM, Kelland LR, Dosanjh HS, Neidle S (1999) Molecular modelling studies on G-quadruplex complexes of telomerase inhibitors: structure-activity relationships. J Med Chem 42, 4538–4546

    CAS  Google Scholar 

  58. Gavathiotis E, Heald RA, Stevens MFG, Searle MS (2003) Drug recognition and stabilisation of the parallel-stranded DNA quadruplex d(TTAGGGT)4 containing the human telomeric repeat. J Mol Biol 334:25–36

    CAS  Google Scholar 

  59. Agrawal S, Ojha RP, Maiti S (2008) Energetics of the human Tel-22 quadruplex-telomestatin interaction: a molecular dynamics study. J Phys Chem B 112:6828–6836

    CAS  Google Scholar 

  60. Hou J-Q, Chen S-B, Tan J-H, Ou T-M, Luo H-B, Li D, Xu J, Gu L-Q, Huaang Z-S (2010) New insights into the structures of ligand-quadruplex complexes from molecular dynamics simulations. J Phys Chem B 114:15301–15310

    CAS  Google Scholar 

  61. Li M-H, Luo Q, Li Z-S (2010) Molecular dynamics study on the interactions of porphyrin with two antiparallel human telomeric quadruplexes. J Phys Chem B 114:6216–6224.

    CAS  Google Scholar 

  62. Li J, Jin X, Hu L, Wang J, Su Z (2011) Identification of nonplanar small molecule for G-quadruplex grooves: molecular docking and molecular dynamic study. Bioorg Med Chem Lett 21:6969–6972

    CAS  Google Scholar 

  63. Hou J-Q, Chen S-B, Tan J-H, Luo H-B, Li D, Gu L-Q, Huaang Z-S. (2012) New insights from molecular dynamic simulation studies of the multiple binding sodes of a ligand with G-quadruplex DNA. J Comput Aided Mol Des 26:1355–1368

    CAS  Google Scholar 

  64. Holt PA, Chaires JB, Trent JO (2008) Molecular docking of intercalators and groove-binders to nucleic acids using Autodock and Surflex. J Chem Inf Model 48:1602–1615

    CAS  Google Scholar 

  65. Ma D-L, Chan DS-H, Lee P, Kwan MH-T, Leung C-H (2011) Molecular modeling of drug-DNA interactions: virtual screening to structure-based design. Biochimie 93:1252–1266

    CAS  Google Scholar 

  66. Ma D-L, Ma VP-Y, Chan DS-H, Leung K-H, Zhong H-J, Leung C-H. (2012) In silico screening of quadruplex-binding ligands. Methods 57:106–114

    CAS  Google Scholar 

  67. Alcaro S, Musetti C, Distinto S, Casatti M, Zagotto G, Artese A, Parrotta L, Moraca F, Costa G, Ortuso F, Maccioni E, Sissi C (2013).Identification and characterization of new DNA G-quadruplex binders selected by a combination of ligand and structure-based virtual screening approaches. J Med Chem 56:843–855

    CAS  Google Scholar 

  68. Haider S, Neidle S (2010) Molecular modeling and simulation of G-quadruplexes and quadruplex-ligand complexes. In: Baumann P. (ed.). G-Quadruplex DNA: Methods and Protocols. Methods Mol Biol, vol 608. Humana Press, New York, p. 17–37

    Google Scholar 

  69. Lee JY, Okumus B, Kim DS, Ha T (2005) Extreme conformational diversity in human telomeric DNA. Proc Natl Acad Sci USA 102:18938–18943

    CAS  Google Scholar 

  70. Burge S, Parkinson GN, Hazel P, Todd AK, Neidle S (2006) Quadruplex DNA: sequence, topology and structure. Nucleic Acids Res. 34:5402–5415

    CAS  Google Scholar 

  71. Dai J, Carver M, Yang D (2008) Polymorphism of human telomeric quadruplex structures. Biochimie 90:1172–1183

    CAS  Google Scholar 

  72. Yang D, Okamoto K (2010) Structural insights into G-quadruplexes: towards new anticancer drugs. Future Med Chem 2:619–646

    CAS  Google Scholar 

  73. Ambrus A, Chen D, Dai J, Bialis T, Jones RA, Yang D (2006) Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution. Nucleic Acids Res 34:2723–2735

    CAS  Google Scholar 

  74. Wang Y, Patel DJ (1993) Solution structure of the human telomeric repeat d[AG3(T2AG3)3] G-tetraplex. Structure 1:263–282

    CAS  Google Scholar 

  75. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera – a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612

    CAS  Google Scholar 

  76. Jain AK, Bhattacharya S (2011) Interaction of G-quadruplexes with nonintercalating duplex-DNA minor groove binding ligands. Bioconjugate Chem. 22:2355–2368

    CAS  Google Scholar 

  77. Trotta R, De Tito S, Lauri I, La Pietra V, Marinelli L, Cosconati S, Martino L, Conte MR, Mayol L, Novellino E, Randazzo A (2011) A more detailed picture of the interactions between virtual screening-derived hits and the DNA G-quadruplex: NMR, molecular modelling and ITC studies. Biochimie 93:1280–1287

    CAS  Google Scholar 

  78. Williamson JR (1994) G-quartet structures in telomeric DNA. Annu Rev Biophys Biomol Struct 23:703–730

    CAS  Google Scholar 

  79. Davies JT (2004) G-quartets 40 years later: from 5’-GMP to molecular biology and supramolecular chemistry. Angew. Chem Int Ed 43:668–698

    Google Scholar 

  80. Riley KE, Hobza P (2011) Noncovalent interactions in biochemistry. Wiley Interdisc. Revs Comput Mol Sci 1:3–17

    CAS  Google Scholar 

  81. Bryan TM, Baumann P (2011) G-Quadruplexes: from guanine gels to chemotherapeutics. Mol. Biotechnol 49:198–208

    CAS  Google Scholar 

  82. Chong DP (ed) (1995) Recent advances in density functional methods. V. 1. recent advances in density functional methods (Part I). World Scientific Publishing, Singapore

    Google Scholar 

  83. Wesolowski TA, Wang YA (eds) (2013) Recent advances in computational chemistry. V. 6. recent progress in orbital-free density functional theory. World Scientific Publishing, Singapore

    Google Scholar 

  84. Jissy AK, Ashik UPM, Datta A (2011) Nucleic acid G-quartets: insights into diverse patterns and optical properties. J Phys Chem C 115:12530–12546

    CAS  Google Scholar 

  85. Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652

    CAS  Google Scholar 

  86. Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785–789

    CAS  Google Scholar 

  87. Zhao Y, Schultz NE, Truhlar DG (2006) Design of density functionals by combining the method of constraint satisfaction with parametrization for thermochemistry, thermochemical kinetics, and noncovalent interactions. J Chem Theory Comput 2:364–382

    Google Scholar 

  88. Zhao Y, Truhlar DG (2008) The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Acc 120:215–241

    CAS  Google Scholar 

  89. Jissy AK, Datta A (2010) Designing molecular switches based on DNA-base mispairing. J Phys Chem B 114:15311–15318

    CAS  Google Scholar 

  90. Kendall RA, Fruchtl HA (1997) The impact of the resolution of the identity approximate integral method on modern ab initio algorithm development. Theor Chem Acc 97:158–163

    CAS  Google Scholar 

  91. Vahtras O, Almlof J, Feyereisen MW (1993) Integral approximations for LCAO-SCF calculations. Chem Phys Lett. 213:514–518

    CAS  Google Scholar 

  92. Schlund S, Schmuck C, Engels B (2005) Knock-out” analogues as a tool to quantify supramolecular processes: a theoretical study of molecular interactions in guanidiniocarbonyl pyrrole carboxylate dimers J Am Chem Soc 127:11115–11124

    CAS  Google Scholar 

  93. Ahlrichs R, Bär M, Häser M, Horn H, Kölmel C (1989) Electronic structure calculations on workstation computers: the program system turbomole. Chem Phys Lett 162:165–169.

    CAS  Google Scholar 

  94. Von Arnim M, Ahlrichs R (1998) Performance of parallel TURBOMOLE for density functional calculations. J Comput Chem 19:1746–1757

    CAS  Google Scholar 

  95. Miertus S, Scrocco, E, Tomasi J (1981) Electrostatic interaction of a solute with a continuum. A direct utilizaion of ab initio molecular potentials for the prevision of solvent effects. Chem Phys 55:117–129

    CAS  Google Scholar 

  96. Ilchenko MM, Dubey I Ya (2011) Density functional study of the structure of guanine octets in aqueous medium. Int Rev Biophys Chem. 2:82–86

    Google Scholar 

  97. Fonseca Guerra C, van der Wijst T, Poater J, Swart M, Bickelhaupt MF (2010) Adenine versus guanine quartets in aqueous solution: dispersion-corrected DFT study on the differences in π-π-stacking and hydrogen-bonding behavior. Theor Chem Acc 125:245–252

    Google Scholar 

  98. Mezzache S, Alves S, Paumard J-P, Pepe C, Tabet J-C (2007) Theoretical and gas-phase studies of specific cationized purine base quartet. Rapid Commun Mass Spectrom 21:1075–1082

    CAS  Google Scholar 

  99. Meyer M, Steinke T, Brandl M, Sühnel J (2001) Density functional study of guanine and uracil quartets and of guanine quartet/metal ion complexes. J Comput Chem 22:109–124

    CAS  Google Scholar 

  100. Meng F, Wang F, Zhao X, Jalbout AF (2008) Guanine tetrad interacting with divalent metal ions (M = Fe2 +, Co2 +, Ni2 +, Cu2 +and Zn2 +): a density functional study. J Mol Struct.: THEOCHEM 854:26–30.

    Google Scholar 

  101. Boys SF, Bernardi F (1970) Calculations of small molecular interaction by the difference of separate total energies. Some procedures with reduced error. Mol Phys 19:553–566

    CAS  Google Scholar 

  102. Bader RFW (1990) Atoms in Molecules: A Quantum Theory. Clarendon Press, Oxford, UK

    Google Scholar 

  103. Rozas I, Alkorta I, Elguero J (1997) Unusual hydrogen bonds: H…π interactions. J Phys Chem A 101:9457–9463

    CAS  Google Scholar 

  104. Deepa P, Kolandaivel P, Senthilkumar K (2011) Structural properties and the effect of interaction of alkali (Li +, Na +, K +) and alkaline earth (Be2 +, Mg2 +, Ca2 +) metal cations with G and SG-tetrads. Comput Theor Chem 974:57–65

    CAS  Google Scholar 

  105. Meng F, Xu W, Liu C (2004) Theoretical study of incorporating 6-thioguanine into a guanine tetrad and their influence on the metal ion–guanine tetrad. Chem. Phys Lett 389:421–426

    CAS  Google Scholar 

  106. Yurenko YeP, Novotný J, Sklenář V, Marek R (2013) Exploring non-covalent interactions in guanine- and xanthine-based model DNA quadruplex structures: A comprehensive quantum chemical approach. Phys. Chem. Chem. Phys. DOI: 10.1039/C3CP53875C

    Google Scholar 

  107. Jissy AK, Datta A (2012) Effect of external electric field on H-bonding and π-stacking interactions in guanine aggregates. Chem Phys Chem 13:4163–4172

    CAS  Google Scholar 

  108. Gu J, Leszczynski J, Bansal M (1999) A new insight into the structure and stability of Hoogsteen hydrogen-bonded G-tetrad: an ab initio SCF study. Chem. Phys Lett 311:209–314

    CAS  Google Scholar 

  109. Gu J, Leszczynski J (2000) A remarkable alteration in the bonding pattern: an HF and DFT study on the interactions between the metal cations and the Hoogsteen hydrogen-bonded G-tetrad. J Phys Chem A 104:6308–6313

    CAS  Google Scholar 

  110. van Mourik T, Dingley AJ (2005) Characterization of the monovalent ion position and hydrogen-bond network in guanine quartets by DFT calculations of NMR parameters. Chem Eur J 11:6064–6079

    CAS  Google Scholar 

  111. Becke AD (1997) Density-functional thermochemistry. V. Systematic optimization of exchange-correlation functionals. J Chem Phys 107:8554–8560

    CAS  Google Scholar 

  112. NWChem (2003) Version 4.5, High Performance Computational Chemistry Group, Pacific Northwest National Laboratory, Richland WA

    Google Scholar 

  113. Szolomájer J, Paragi G, Batta G, Fonseca Guerra C, Bickelhaupt FM, Kele Z, Pádár P, Kupihára Z, Kovács L (2011) 3-Substituted xanthines as promising candidates for quadruplex formation: computational, synthetic and analytical studies. New J Chem 35:486–482

    Google Scholar 

  114. Meyer M, Hocquet A, Sühnel J (2005) Interaction of sodium and potassium ions with sandwiched cytosine-, guanine-, thymine-, and uracil-base tetrads. J Comput Chem 26:352–364

    CAS  Google Scholar 

  115. Meyer M, Steinke T, Sühnel J (2007) Density functional study of isoguanine tetrad and pentad sandwich complexes with alkali metal ions. J Mol Model 13:335–345

    CAS  Google Scholar 

  116. Hua Y, Changenet-Barret P, Improta R, Vaya I, Gustavsson T, Kotlyar AB, Zikich D, Šket P, Plavec J, Markovitsi D (2012) Cation effect on the electronic excited states of guanine nanostructures studied by time-resolved fluorescence spectroscopy. J Phys Chem C 116:14682–14689

    CAS  Google Scholar 

  117. Liu H, Gauld JW (2009) Protonation of guanine quartets and quartet stacks: insights from DFT studies. Phys Chem Chem Phys 11:278–287

    CAS  Google Scholar 

  118. Lech CJ, Heidi B, Phan AT (2013) Guanine base stacking in G-quadruplex nucleic acids. Nucl Acids Res 41:2034–2046

    CAS  Google Scholar 

  119. Šponer J, Mládek A, Špačková N, Cang X, Cheatham TE, Grimme S (2013) Relative stability of different DNA guanine quadruplex stem topologies derived using large-scale quantum-chemical computations. J Am Chem Soc 135:9785–9796

    Google Scholar 

  120. Fonseca Guerra C, Zijlstra H, Paragi G, Bickelhaupt FM (2011) Telomere structure and stability: Covalency in hydrogen bonds, not resonance assistance, causes cooperativity in guanine quartets. Chem Eur J 17:12612–12622

    CAS  Google Scholar 

  121. Warshel A. (1991). Computer Modeling of Chemical Reactions in Enzymes and Solutions. John Wiley, New York.

    Google Scholar 

  122. Acevedo O, Jorgensen WL (2010) Advances in quantum and molecular mechanical (QM/MM) simulations for organic and enzymatic reactions. Acc Chem Res 43:142–151

    CAS  Google Scholar 

  123. Banáš P, Jurečka P, Walter NG, Šponer J, Otyepka M (2009) Theoretical studies of RNA catalysis: hybrid QM/MM methods and their comparison with MD and QM. Methods 49:202–216

    Google Scholar 

  124. Clay EH, Gould IR (2005) A combined QM and MM investigation into guanine quadruplexes J Mol Graph Model 24:138–146

    CAS  Google Scholar 

  125. Pearlman DA, Case DA, Caldwell JW, Ross WS, Cheatham TE III, DeBolt S, Ferguson D, Seibel G, Kollman P (1995) AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules. Comput Phys Comm 91:1–41

    CAS  Google Scholar 

  126. Cornell WD, Cieplak P, Bayly CI, Gould IR, Merz KM, Ferguson DM, Spellmeyer DC, Fox T, Caldwell JW, Kollman PA (1995) A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J Am Chem Soc 117:5179–5197

    CAS  Google Scholar 

  127. Ferreira R, Artali R, Benoit A, Gargallo R, Eritja R, Ferguson DM, Sham YY, Mazzini S (2013) Structure and stability of human telomeric G-quadruplex with preclinical 9-amino acridines. PLOS One, 8, e57701. doi: 10.1371/journal.pone.0057701

    CAS  Google Scholar 

  128. Subramanian AK, Cardin CJ (2012) Molecular modelling studies of binding of DACD derivatives into G-quadruplex DNA: comparison of force field and quantum polarized ligand docking methods. Int J Pharm Pharm Sci 4:509–514

    CAS  Google Scholar 

  129. Glide (2009) version 5.5, Schrodinger, Inc, New York

    Google Scholar 

  130. Jaguar (2011) version 7.8, Schrodinger, Inc, New York

    Google Scholar 

  131. Dubey LV, Ilchenko MM, Zozulya VN, Ryazanova OA, Pogrebnoy PV, Dubey IYa (2011) Synthesis, structure and antiproliferative activity of cationic porphyrin-imidazophenazine conjugate. Int Rev Biophys Chem 2:147–152

    Google Scholar 

  132. Zhao Y, Truhlar DG (2006) Comparative DFT study of van der Waals complexes: rare-gas dimers, alkaline-earth dimers, zinc dimer, and zinc-rare-gas dimers. J Phys Chem A 110:5121–5129

    CAS  Google Scholar 

  133. Cossi M, Scalmani G, Rega N, Barone V (2002) New developments in the polarizable continuum model for quantum mechanical and classical calculations on molecules in solution. J Chem Phys 117:43–54

    CAS  Google Scholar 

  134. Zozulya VN, Ryazanova OA, Voloshin IM, Dubey LV, Dubey IYa (2011) Spectroscopic studies on binding of porphyrin-phenazine conjugate to intramolecular G-quadruplex formed by 22-mer oligonucleotide. Int Rev Biophys Chem 2:112–119

    Google Scholar 

  135. Negrutska VV, Dubey LV, Ilchenko MM, Dubey IYa (2013) Design and study of telomerase inhibitors based on G-quadruplex ligands. Biopolym. Cell 29:169–176

    CAS  Google Scholar 

  136. Nicoludis JM, Miller ST, Jeffrey PD, Barrett SP, Rablen PR, Lawton TJ, Yatsunyk LA (2012) Optimized end-stacking provides specificity of N-methyl mesoporphyrin IX for human telomeric G-quadruplex DNA. J Am Chem Soc 134:20446–20456

    CAS  Google Scholar 

  137. König SLB, Evans AC, Huppert JL (2010) Seven essential questions on G-quadruplexes. BioMol Concepts 1:197–213

    Google Scholar 

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Acknowledgments

Molecular visualization was performed with the UCSF Chimera package developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIGMS P41-GM103311).

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Authors and Affiliations

  1. Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Zabolotnogo str., 03680, Kyiv, Ukraine

    Mykola Ilchenko & Igor Dubey

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  1. Mykola Ilchenko
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  2. Igor Dubey
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Correspondence to Igor Dubey .

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  1. Department of Molecular Biophysics, Laboratory of Computational Structural Biology, Kiev, Ukraine

    Leonid Gorb

  2. Department of Molecular Structure and Chemoinformatics, A.V. Bogatsky Physical-Chemical Institute, National Academy of Sciences of Ukraine, Odessa, Ukraine

    Victor Kuz'min

  3. Department of Chemical Biology and Medicinal Chemistry, University of North Carolina, Laboratory for Molecular Modeling, Chapel Hill, North Carolina, USA

    Eugene Muratov

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Ilchenko, M., Dubey, I. (2014). Quantum Chemical Approaches in Modeling the Structure of DNA Quadruplexes and Their Interaction with Metal Ions and Small Molecules. In: Gorb, L., Kuz'min, V., Muratov, E. (eds) Application of Computational Techniques in Pharmacy and Medicine. Challenges and Advances in Computational Chemistry and Physics, vol 17. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-9257-8_6

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