Skip to main content
SpringerLink
Log in

The nature of base stacking: a Monte Carlo study

  • Regular Article
  • Published:
Theoretical Chemistry Accounts Aims and scope Submit manuscript

Abstract

To elucidate the physical origin of the preference of nucleic acid bases for stacking over hydrogen bonding in water, Monte Carlo simulations were performed starting from Watson–Crick structures of the adenine–thymine, adenine–uracil and guanine–cytosine base pairs, as well as from the Hoogsteen adenine–thymine base pair, in clusters comprising 400 and 800 water molecules. The simulations employed a newly implemented Metropolis Monte Carlo algorithm based on the extended cluster approach. All simulations reached stacked structures, confirming that such structures are preferred over the hydrogen-bonded Watson–Crick and Hoogsteen base pairs. The Monte Carlo simulations show the complete transition from hydrogen-bonded base pairs to stacked structures in the Monte Carlo framework. Analysis of the average energies shows that the preference of stacked over hydrogen-bonded structures is due to the increased water–base interaction in these structures. This is corroborated by the increased number of water–base hydrogen bonds in the stacked structures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Schultze P, Smith FW, Feigon J (1994) Refined solution structure of the dimeric quadruplex formed from the Oxytricha telomeric oligonucleotide d(GGGGTTTTGGGG). Structure 2:221–233

    Article  CAS  Google Scholar 

  2. Yakovchuk P, Protozanova E, Frank-Kamenetskii MD (2006) Base-stacking and base-pairing contributions into thermal stability of the DNA double helix. Nucleic Acids Res 34:564–574

    Article  CAS  Google Scholar 

  3. Nakano NI, Igarashi SJ (1970) Molecular interactions of pyrimidines, purines, and some other heteroaromatic compounds in aqueous media. Biochemistry 9:577–583

    Article  CAS  Google Scholar 

  4. Ts’o POP, in: P.O.P. Ts’o (ed) (1974) Basic principles in nucleic acid chemistry. Academic Press, London, p 453

  5. Sinnokrot MO, Sherrill CD (2004) Substituent effects in π–π interactions: sandwich and T-shaped configurations. J Am Chem Soc 126:7690–7697

    Article  CAS  Google Scholar 

  6. Sinnokrot MO, Sherrill CD (2004) Highly accurate coupled cluster potential energy curves for the benzene dimer: sandwich, T-shaped, and parallel-displaced configurations. J Phys Chem A 108:10200–10207

    Article  CAS  Google Scholar 

  7. Hill JG, Platts JA, Werner H-J (2006) Calculation of intermolecular interactions in the benzene dimer using coupled-cluster and local correlation methods. Phys Chem Chem Phys 8:4072–4078

    Article  CAS  Google Scholar 

  8. Ringer AL, Sinnokrot MO, Lively RP, Sherrill CD (2006) The effect of multiple substituents on sandwich and T-shaped pi–pi interactions. Chem Eur J 12:3821–3828

    Article  CAS  Google Scholar 

  9. Sinnokrot MO, Sherrill CD (2006) High-accuracy quantum mechanical studies of pi–pi interactions in benzene dimers. J Phys Chem A 110:10656–10668

    Article  CAS  Google Scholar 

  10. Arnstein SA, Sherrill CD (2008) Substituent effects in parallel-displaced pi–pi interactions. Phys Chem Chem Phys 10:2646–2655

    Article  CAS  Google Scholar 

  11. Ringer AL, Sherrill CD (2009) Substituent effects in sandwich configurations of multiply substituted benzene dimers are not solely governed by electrostatic control. J Am Chem Soc 131:4574–4575

    Article  CAS  Google Scholar 

  12. Takatani T, Sherrill CD (2007) Performance of spin-component-scaled Møller-Plesset theory (SCS-MP2) for potential energy curves of noncovalent interactions. Phys Chem Chem Phys 9:6106–6114

    Article  CAS  Google Scholar 

  13. Sherrill CD, Takatani T, Hohenstein EG (2009) An assessment of theoretical methods for nonbonded interactions: comparison to complete basis set limit coupled-cluster potential energy curves for the benzene dimer, the methane dimer, benzene-methane, and benzene-H2S. J Phys Chem A 113:10146–10159

    Article  CAS  Google Scholar 

  14. Vazquez-Mayagoitia A, Sherrill CD, Apra E, Sumpter BG (2010) An assessment of density functional methods for potential energy curves of nonbonded interactions: the XYG3 and B97-D approximations. J Chem Theor Comput 6:727–734

    Article  CAS  Google Scholar 

  15. Jurečka P, Nachtigall P, Hobza P (2001) RI-MP2 calculations wih extended basis sets—a promising tool for study of H-bonded and stacked DNA base pairs. Phys Chem Chem Phys 3:4578–4582

    Article  Google Scholar 

  16. Hobza P, Sponer J (2002) Toward true DNA base-stacking energies: MP2, CCSD(T) and complete basis set calculations. J Am Chem Soc 124:11802–11808

    Article  CAS  Google Scholar 

  17. Leininger ML, Nielsen IMB, Colvin ME, Janssen CL (2002) Accurate structures and binding energies for stacked uracil dimers. J Phys Chem A 106:3850–3854

    Article  CAS  Google Scholar 

  18. Dąbkowska I, Jurecka P, Hobza P (2005) On geometries of stacked and H-bonded nucleic acid base pairs determined at various DFT, MP2, and CCSD(T) levels up to the CCSD(T)/complete basis set level. J Chem Phys 122:204322

    Article  Google Scholar 

  19. Pitoňák M, Riley KE, Neogrády P, Hobza P (2008) Highly accurate CCSD(T) and DFT-SAPT stabilization energies of H-bonded and stacked structures of the uracil dimer. ChemPhysChem 9:1636–1644

    Article  Google Scholar 

  20. Czyznikowska Z (2009) On the importance of electrostatics in stabilization of stacked guanine-adenine complexes appearing in B-DNA crystals. J Mol Struct (Theochem) 895:161–167

    Article  CAS  Google Scholar 

  21. Sivanesan D, Babu K, Gadre SR, Subramanian V, Ramasami T (2000) Does a stacked DNA base pair hydrate better than a hydrogen-bonded one?: an ab initio study. J Phys Chem A 104:10887–10894

    Article  CAS  Google Scholar 

  22. Sivanesan D, Sumathi I, Welsh WJ (2003) Comparative studies between hydrated hydrogen bonded and stacked DNA base pair. Chem Phys Lett 367:351–360

    Article  CAS  Google Scholar 

  23. Kabeláč M, Zendlová L, Řeha D, Hobza P (2005) Potential energy surfaces of an adenine–thymine base pair and its methylated analogue in the presence of one and two water molecules: molecular mechanics and correlated ab Initio study. J Phys Chem B 109:12206–12213

    Article  Google Scholar 

  24. Dkhissi A, Blossey R (2008) Metahybrid density functional theory and correlated ab initio studies on microhydrated adenine–thymine base pairs. J Phys Chem B 112:9182–9186

    Article  CAS  Google Scholar 

  25. Friedman RA, Honig B (1995) A free-energy analysis of nucleic-acid base stacking in aqueous-solution. Biophys J 69:1528–1535

    Article  CAS  Google Scholar 

  26. Danilov VI, van Mourik T, Kurita N, Wakabayashi H, Tsukamoto T, Hovorun DM (2009) On the mechanism of the mutagenic action of 5-bromouracil: a DFT study of uracil and 5-bromouracil in a water cluster. J Phys Chem A 113:2233–2235

    Article  CAS  Google Scholar 

  27. van Mourik T, Danilov VI, Dailidonis VV, Kurita N, Wakabayashi H, Tsukamoto T (2010) A DFT study of uracil and 5-bromouracil in nanodroplets. Theor Chem Acc 125:233–244

    Article  CAS  Google Scholar 

  28. Palafox MA, Iza N, de la Fuente M, Navarro R (2009) Simulation of the first hydration shell of nucleosides D4T and thymidine: structures obtained using MP2 and DFT methods. J Phys Chem B 113:2458–2476

    Article  CAS  Google Scholar 

  29. Tajkhorshid E, Jalkanen KJ, Suhai S (1998) Structure and vibrational spectra of the zwitterion l-alanine in the presence of explicit water molecules: a density functional analysis. J Phys Chem B 102:5899–5913

    Article  CAS  Google Scholar 

  30. Han W-G, Jalkanen KJ, Elstner M, Suhai S (1998) Theoretical study of aqueous N-acetyl-l-alanine N′-methylamide: structures and Raman, VCD, and ROA spectra. J Phys Chem B 102:2587–2602

    Article  CAS  Google Scholar 

  31. Frimand K, Bohr H, Jalkanen KJ, Suhai S (2000) Structures, vibrational absorption and vibrational circular dichroism spectra of image-alanine in aqueous solution: a density functional theory and RHF study. Chem Phys 255

  32. Jalkanen KJ, Nieminen RM, Frimand K, Bohr J, Bohr H, Wade RC, Tajkhorshid E, Suhai S (2001) A comparison of aqueous solvent models used in the calculation of the Raman and ROA spectra of image-alanine. Chem Phys 265:125–151

    Article  CAS  Google Scholar 

  33. Jalkanen KJ, Würtz Jürgensen V, Claussen A, Rahim A, Jensen GM, Wade RC, Nardi F, Jung C, Degtyarenko IM, Nieminen RM, Herrmann F, Knapp-Mohammady M, Niehaus TA, Frimand K, Suhai S (2006) Use of vibrational spectroscopy to study protein and DNA structure, hydration, and binding of biomolecules: a combined theoretical and experimental approach. Int J Quant Chem 106:1160–1198

    Article  CAS  Google Scholar 

  34. Jürgensen VW, Jalkanen K (2006) The VA, VCD, Raman and ROA spectra of tri-l-serine in aqueous solution. Phys Biol 3:S63

    Article  Google Scholar 

  35. Losada M, Xu Y (2007) Chirality transfer through hydrogen-bonding: experimental and ab initio analyses of vibrational circular dichroism spectra of methyl lactate in water. Phys Chem Chem Phys 9:3127–3135

    Article  CAS  Google Scholar 

  36. Deplazes E, van Bronswijk W, Zhu F, Barron L, Ma S, Nafie L, Jalkanen K (2008) A combined theoretical and experimental study of the structure and vibrational absorption, vibrational circular dichroism, Raman and Raman optical activity spectra of the l-histidine zwitterion. Theor Chem Acc 119:155–176

    Article  CAS  Google Scholar 

  37. Jalkanen KJ, Degtyarenko IM, Nieminen RM, Cao X, Nafie LA, Zhu F, Barron LD (2008) Role of hydration in determining the structure and vibrational spectra of l-alanine and N-acetyl l-alanine N′-methylamide in aqueous solution: a combined theoretical and experimental approach. Theor Chem Acc 119:191–210

    Article  CAS  Google Scholar 

  38. Mukhopadhyay P, Zuber G, Beratan DN (2008) Characterizing aqueous solution conformations of a peptide backbone using Raman optical activity computations. Biophys J 95:5574–5586

    Article  CAS  Google Scholar 

  39. van Mourik T (2006) Density functional theory reveals an increase in the amino 1H chemical shift in guanine due to hydrogen bonding with water. J Chem Phys 125:191101

    Article  Google Scholar 

  40. Degtyarenko IM, Jalkanen KJ, Gurtovenko AA, Nieminen RM (2007) l-Alanine in a droplet of water: a density-functional molecular dynamics study. J Phys Chem B 111:4227–4234

    Article  CAS  Google Scholar 

  41. Sykes MT, Levitt M (2007) Simulations of RNA base pairs in a nanodroplet reveal solvation-dependent stability. PNAS 104:12336–12340

    Article  CAS  Google Scholar 

  42. Stewart JJP (2007) Optimization of parameters for semiempirical methods V: modification of NDDO approximations and application to 70 elements. J Mol Model 13:1173–1213

    Article  CAS  Google Scholar 

  43. Dang LX, Kollman PA (1990) Molecular dynamics simulations study of the free energy of association of 9-methyladenine and 1-methylthymine bases in water. J Am Chem Soc 112:503–507

    Article  CAS  Google Scholar 

  44. Danilov VI, Dailidonis VV, van Mourik T, Früchtl HA (2011) A study of nucleic acid base-stacking by the Monte Carlo method: extended cluster approach. Centr Eur J Chem 9:720–727

    Article  CAS  Google Scholar 

  45. Danilov VI, Dailidonis VV, van Mourik T, Früchtl HA (2011) The study of the nucleic acid base-stacking by Monte Carlo method: extended cluster approach. J Biomol Struct Dyn 28:1140–1141 (Book of Abstracts: Albany 2011, Conversation 17, June 14–18 2011). http://www.jbsdonline.com/The-Study-of-the-Nucleic-Acid-Base-Stacking-by-Monte-Carlo-Method-Extended-Cluster-Approach-p18003.html

  46. Cieplak P, Kollman PA (1988) Calculation of the free-energy of association of nucleic-acid bases in vacuo and water solution. J Am Chem Soc 110:3734–3739

    Article  CAS  Google Scholar 

  47. Danilov VI, Tolokh IS (1984) Nature of the stacking of nucleotide bases in water—a Monte Carlo simulation. J Biomol Struct Dyn 2:119–130

    CAS  Google Scholar 

  48. Danilov VI, Tolokh IS (1984) On the role of hydrophobic groups in nucleotide base stacking—a Monte-Carlo study of hydration of thymine dimers. FEBS Lett 173:347–350

    Article  CAS  Google Scholar 

  49. Danilov VI, Tolokh IS, Poltev VI (1984) A Monte Carlo study of the hydration of thymine molecule associates. FEBS Lett 171:325–328

    Article  CAS  Google Scholar 

  50. Danilov VI, Tolokh IS, Poltev VI, Malenkov GG (1984) Nature of the stacking interaction of nucleotide bases in water—a Monte-Carlo study of the hydration of uracil molecule associates. FEBS Lett 167:245–248

    Article  CAS  Google Scholar 

  51. Pohorille A, Burt SK, MacElroy RD (1984) Monte Carlo simulation of the influence of solvent on nucleic acid base associations. J Am Chem Soc 106:402–409

    Article  CAS  Google Scholar 

  52. Pohorille A, Pratt LR, Burt SK, MacElroy RD (1984) Solution influence on biomolecular equilibria—nucleic-acid base associations. J Biomol Struct Dyn 1:1257–1280

    CAS  Google Scholar 

  53. Danilov VI, Tolokh IS (1985) Nature of the stacking of nucleic acid bases in water: a Monte Carlo study. J Mol Struct (THEOCHEM) 123:109–119

    Article  Google Scholar 

  54. Danilov VI (1986) Application of the Monte Carlo method for studying the hydration of molecules: base stacking. J Mol Struct (THEOCHEM) 138:239–242

    Article  Google Scholar 

  55. Danilov VI (1986) In: Trinajstic N (ed) Mathematics and computational concepts in chemistry. Elis Horwood Lmd, Chichester, p 48

    Google Scholar 

  56. Lee JK, Barker JA, Abraham FF (1973) Theory and Monte Carlo simulation of physical clusters in the imperfect vapor. J Chem Phys 58:3166–3180

    Article  CAS  Google Scholar 

  57. Abraham FF (1974) Monte Carlo simulation of physical clusters of water molecules. J Chem Phys 61:1221–1225

    Article  CAS  Google Scholar 

  58. Abraham FF, Mruzik MR, Pound GM (1976) The thermodynamics and structure of hydrated halide and alkali ions. Faraday Discuss Chem Soci 61:34–47

    Article  CAS  Google Scholar 

  59. Mruzik MR, Abraham FF, Schreiber DE, Pound GM (1976) A Monte Carlo study of ion-water clusters. J Chem Phys 64:481–491

    Article  CAS  Google Scholar 

  60. Mruzik MR (1977) A Monte Carlo study of water clusters. Chem Phys Lett 48:171–175

    Article  CAS  Google Scholar 

  61. Metropolis N, Rosenbluth AW, Rosenbluth MN, Teller AH, Teller E (1953) J Chem Phys 21:1087–1092

    Article  CAS  Google Scholar 

  62. Poltev VI, Grokhlina TI, Malenkov GG (1984) Hydration of nucleic-acid bases studied using novel atom–atom potential functions. J Biomol Struct Dyn 2:413–429

    CAS  Google Scholar 

  63. González-Jiménez E, Castro-Valdez I, López-Apresa E, Filippov SV, Teplukhin AV, Poltev VI (1999) Computer study of the role of hydration in the accuracy of nucleic acid biosynthesis. J Mol Struct (Theochem) 493:301–308

    Article  Google Scholar 

  64. González E, Cedeño FI, Teplukhin AV, Malenkov GG, Poltev VI (2000) Refinement of methodology for simulation of nucleic acid hydration. Rev Mex Fis 46:142–147

    Google Scholar 

  65. Poltev VI, Deryabina AS, González E, Grokhlina TI (2002) Interactions between nucleic acid bases. New parameters of potential functions and new energy minima. Biofizika 47:996–1004

    CAS  Google Scholar 

  66. Zhurkin VB, Poltev VI, Florentev VL (1980) Atom-atom potential functions for conformational calculations of nucleic-acids. Mol Biol 14:882–895

    Google Scholar 

  67. Poltev VI, Shulyupina NV (1986) Simulation of interactions between nucleic-acid bases by refined atom–atom potential functions. J Biomol Struct Dyn 3:739–765

    CAS  Google Scholar 

  68. Poltev VI, Malenkov GG, Gonzalez EJ, Teplukhin A, Rein R, Shibata M, Miller JH (1996) Modeling DNA hydration: comparison of calculated and experimental hydration properties of nucleic acid bases. J Biomol Struct Dyn 13:717–725

    CAS  Google Scholar 

  69. Grimme S, Antony J, Ehrlich S, Krieg H (2010) A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu. J Chem Phys 132:154104

    Article  Google Scholar 

  70. TURBOMOLE V6.0 2009, a development of University of Karlsruhe and Forschungszentrum Karlsruhe GmbH, 1989–2007, TURBOMOLE GmbH, since 2007. Available from http://www.turbomole.com

  71. Dailidonis VV, Danilov VI (2010) The extended cluster approach in the Metropolis-Monte Carlo algorithm, see http://www.biophys.in.ua/

  72. El Hassan MA, Calladine CR (1997) Conformational characteristics of DNA: empirical classifications and a hypothesis for the conformational behaviour of dinucleotide steps. Phil Trans Roy Soc Lond A 355:43–100

    Article  CAS  Google Scholar 

  73. Danilov VI, Stewart JPP, van Mourik T (2007) A PM6 study of the “hydration shell” of nucleic acid bases in small water clusters. J Biomol Struct Dyn 24:652–653 (Book of Abstracts: Albany 2007, Conversation 15, June 19–23 2007). http://www.jbsdonline.com/A-PM6-Study-of-the-Hydration-Shell-of-Nucleic-Acid-Bases-in-Small-Water-Clusters-p15619.html

  74. Gusarov S, Malmqvist P-Å, Lindh R, Roos BO (2004) Correlation potentials for a multiconfigurational-based density functional theory with exact exchange. Theor Chem Acc 112:84–94

    Article  CAS  Google Scholar 

  75. Gräfenstein J, Cremer D (2005) Development of a CAS-DFT method covering non-dynamical and dynamical electron correlation in a balanced way. Mol Phys 103:279–308

    Google Scholar 

  76. Weimer M, Sala FD, Görling A (2008) Multiconfiguration optimized effective potential method for a density-functional treatment of static correlation. J Chem Phys 128:144109

    Article  Google Scholar 

Download references

Acknowledgments

We are grateful to Professor Stefan Grimme for providing us with BLYP-D3 energies for the AT, AU and GC stacks. TvM and HAF thank EaStCHEM for support via the EaStCHEM Research Computing Facility. TvM and VID acknowledge financial support from the Royal Society through an International Joint Project grant.

Author information

Authors and Affiliations

  1. Bogolyubov Institute for Theoretical Physics, National Academy of Sciences of Ukraine, 14b Metrologicheskaya Street, Kyiv-143, 03143, Ukraine

    Vladimir V. Dailidonis

  2. Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Zabolotny Street, Kyiv-143, 03143, Ukraine

    Victor I. Danilov

  3. School of Chemistry, University of St. Andrews, North Haugh, St. Andrews, Fife, KY16 9ST, Scotland, UK

    Herbert A. Früchtl & Tanja van Mourik

Authors
  1. Vladimir V. Dailidonis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Victor I. Danilov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Herbert A. Früchtl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tanja van Mourik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tanja van Mourik.

Additional information

Dedicated to Professor Akira Imamura on the occasion of his 77th birthday and published as part of the Imamura Festschrift Issue.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 66 kb)

Supplementary material 2 (MPG 1,522 kb)

Supplementary material 3 (MPG 1,326 kb)

Supplementary material 4 (MPG 1,484 kb)

Supplementary material 5 (MPG 1,436 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dailidonis, V.V., Danilov, V.I., Früchtl, H.A. et al. The nature of base stacking: a Monte Carlo study. Theor Chem Acc 130, 859–870 (2011). https://doi.org/10.1007/s00214-011-1046-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00214-011-1046-1

Keywords

Search

Navigation