Skip to main content
SpringerLink
Log in

A hydrophobic similarity analysis of solvation effects on nucleic acid bases

  • Original paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

We investigate the changes in the solvation properties of the natural nucleic acid bases due to the formation of the canonical Watson–Crick hydrogen-bonded complexes. To this end, the changes in the free energy of solvation of the bases induced upon hydrogen-bonded dimerization are analyzed by means of the hydrophobic similarity index, which relies on the atomic contributions to the free energy of solvation determined by the partitioning method implemented in the framework of the MST continuum model. Such an index is also used to examine the hydrophobic similarity between the canonical nucleic acid bases and a series of highly apolar analogues, which have been designed as potential candidates to expand the genetic alphabet. The ability of these analogues to be incorporated into modified DNA duplexes can be related to the large reduction in the hydrophilicity of the natural bases upon formation of the canonical hydrogen-bonded dimers. The results illustrate the suitability of the hydrophobic similarity index to rationalize the role played by solvation in molecular recognition.

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

Similar content being viewed by others

References

  1. Bleicher KH, Bohm HJ, Muller K, Alanine AI (2003) Nat Rev Drug Discov 52:369–378

    Article  Google Scholar 

  2. Schuffenhauer A, Popov M, Schopfer U, Acklin P, Stanek J, Jacoby E (2004) Comb Chem High Throughput Screen 7:771–781

    Article  CAS  Google Scholar 

  3. Dean PM (ed) (1995) Molecular similarity in drug design. Blackie Academic, London

    Google Scholar 

  4. Johnson MA, Maggiora GM (eds) (1990) Concepts and applications of molecular similarity. Wiley, New York

    Google Scholar 

  5. Carbó-Dorca R, Gironés X, Mezey PG (eds) (2001) Fundamentals of molecular similarity. Kluwer Academic/Plenum Publishers, New York

    Google Scholar 

  6. Carbó R, Leyda L, Arnau M (1980) Int J Quant Chem 17:1185–1189

    Article  Google Scholar 

  7. Carbó-Dorca R, Robert D, Amat L, Girones X, Besalú E (2000) Lecture notes in chemistry, vol 73. Springer, Berlin, Hiedelberg, New York

    Google Scholar 

  8. Lee C, Smithline S (1994) J Phys Chem 98:1135–1138

    Article  CAS  Google Scholar 

  9. Bowen-Jenkins PE, Richards WG (1986) J Chem Soc, Chem Commun 133–135

  10. Popelier PLA (1999) J Phys Chem A 103:2883–2890

    Article  CAS  Google Scholar 

  11. O’Brien SE, Popelier PLA (1999) Can J Chem 77:28–36

    Article  CAS  Google Scholar 

  12. Kier LB, Hall LH (1986) Molecular connectivity letchworkin structure-activity analysis. Research Studies, Letchwork

    Google Scholar 

  13. Hall LH, Kier LB (1991) The molecular connectivity chi indexes and kappa shape indexes in structure-property relations. In: Lipkowitz KB, Boyd DB (eds) Reviews in Computational Chemistry, vol 2. VCH, New York pp 367–442

    Chapter  Google Scholar 

  14. Luque FJ, Sanz F, Illas F, Pouplana R, Smeyers YG (1988) Eur J Med Chem 23:7–10

    Article  CAS  Google Scholar 

  15. Richard AM (1991) J Comput Chem 12:959–969

    Article  CAS  Google Scholar 

  16. Hernández B, Orozco M, Luque FJ (1996) J Comput Aided Mol Des 10:535–544

    Article  Google Scholar 

  17. Náray-Szabó G, Ferenczy GG (1995) Chem Rev 95:829–847

    Article  Google Scholar 

  18. Hodgkin EE, Richards WG (1987) Int J Quant Chem 14:105–110

    Article  CAS  Google Scholar 

  19. Burt C, Richards WG, Huxley P (1990) J Comput Chem 11:1139–1146

    Article  CAS  Google Scholar 

  20. Manaut F, Sanz F, José J, Milesi M (1991) J Comput Aided Mol Des 5:371–380

    Article  CAS  Google Scholar 

  21. Petke JD (1993) J Comput Chem 8:928–933

    Article  Google Scholar 

  22. Rodríguez J, Manaut F, Sanz F (1993) J Comput Chem 14:922–927

    Article  Google Scholar 

  23. Thorner DA, Willet P, Wright PM, Taylor R (1997) J Comput Aided Mol Des 11:163–174

    Article  CAS  Google Scholar 

  24. Meyer AM, Richards WG (1991) J Comput Aided Mol Des 5:427–439

    Article  CAS  Google Scholar 

  25. Mezey PG (1993) Shape in chemistry: an introduction to molecular shape and topology. VCH, New York

    Google Scholar 

  26. Tokarski JS, Hopfinger AJ (1994) J Med Chem 37:3639–3654

    Article  CAS  Google Scholar 

  27. Jain N, Dietterich TG, Lathrop RH, Chapman D, Critchlow Jr RE, Bauer BE, Webster TA, Lozano-Pérez T (1994) J Comput Aided Mol Des 8:635–652

    Article  CAS  Google Scholar 

  28. Cramer RD III, Paterson DE, Bunce JD (1988) J Am Chem Soc 110:5959–5967

    Article  CAS  Google Scholar 

  29. Klebe G, Mietzner T, Weber F (1994) J Comput Aided Mol Des 8:751–778

    Article  CAS  Google Scholar 

  30. Perkins TDJ, Mills JEJ, Dean PM (1995) J Comput Aided Mol Des 9:479–490

    Article  CAS  Google Scholar 

  31. Mestres J, Rohrer DC, Maggiora GM (1997) J Comput Chem 18:934–954

    Article  CAS  Google Scholar 

  32. Kubinyi H (ed) 3D QSAR in drug design: theory, methods and applications. (1993) ESCOM, Leiden

    Google Scholar 

  33. Lemmen C, Lengauer T, Klebe G (1998) J Med Chem 41:4502–4520

    Article  CAS  Google Scholar 

  34. Miller MD, Sheridan RP, Kearsley K (1999) J Med Chem 42:1505–1514

    Article  CAS  Google Scholar 

  35. Palm K, Luthman K, Ungell AL, Strandlund G, Artursson P (1996) J Pharm Sci 85:32–39

    Article  CAS  Google Scholar 

  36. Palm K, Luthman K, Ungell AL, Strandlund G, Beigi F, Lundahl P, Artursson P (1998) J Med Chem 41:5382–5392

    Article  CAS  Google Scholar 

  37. Clark DE (1999) J Pharm Sci 88:807–814

    Article  CAS  Google Scholar 

  38. Clark DE (1999) J Pharm Sci 88:815–821

    Article  CAS  Google Scholar 

  39. Kantola A, Villar HO, Loew GH (1991) J Comput Chem 12:681–689

    Article  CAS  Google Scholar 

  40. Segarra V, López M, Ryder H, Palacios JM (1999) Quant Struct- Act Relatsh 18:474–481

    Article  CAS  Google Scholar 

  41. Sulea T, Purísima EO (1999) Quant Struct- Act Relatsh 18:154–158

    Article  CAS  Google Scholar 

  42. Eisenberg D, McLachlan AD (1986) Nature 319:199–203

    Article  CAS  Google Scholar 

  43. Eisenberg D, Schwarz E, Komaromy M, Wall R (1984) J Mol Biol 179:125–142

    Article  CAS  Google Scholar 

  44. Barril X, Muñoz J, Luque FJ, Orozco M (2000) Phys Chem Chem Phys 2:4897–4905

    Article  CAS  Google Scholar 

  45. Muñoz J, Barril X, Luque FJ, Gelpí JL, Orozco M (2001) Partitioning of free energies of solvation into fragment contributions: applications in drug design. In: Carbó-Dorca R, Gironés X, Mezey PG (eds) Fundamentals of molecular similarity. Kluwer Academic Plenum Publishers, New York pp 143–168

    Google Scholar 

  46. Audry E, Dubost JP, Colleter JC, Dallet P (1986) Eur J Med Chem 21:71–72

    CAS  Google Scholar 

  47. Brasseur R (1991) J Biol Chem 266:16120–16127

    CAS  Google Scholar 

  48. Heiden FW, Moeckel G, Brickmann J (1993) J Comput Aided Mol Des 7:503–514

    Article  CAS  Google Scholar 

  49. Kellogg E, Semus SF, Abraham DJ (1991) J Comput Aided Mol Des 5:545–552

    Article  CAS  Google Scholar 

  50. Gaillard P, Carrupt PA, Testa B, Boudon A (1994) J Comput Aided Mol Des 8:83–96

    Article  CAS  Google Scholar 

  51. Furet P, Sele A, Cohén, NCJ (1988) J Mol Graph 6:182–189

    Article  CAS  Google Scholar 

  52. Croizet F, Langlois MH, Dubost JP, Braquet P, Audry E, Dallet P, Colleter JC (1990) J Mol Graph 8:153–155

    Article  CAS  Google Scholar 

  53. Fauchére JL, Quarendon P, Kaetterer L (1988) J Mol Graph 6:203–206

    Article  Google Scholar 

  54. Du Q, Arteca GA (1996) J Comput Aided Mol Des 10:133–144

    Article  CAS  Google Scholar 

  55. Du Q, Arteca GA, Mezey PG (1997) J Comput Aided Mol Des 11:503–516

    Article  CAS  Google Scholar 

  56. Bone RGA, Villar HO (1995) J Mol Graph 13:201–208

    Article  CAS  Google Scholar 

  57. Muñoz J, Hernández B, Barril X, Orozco M, Luque FJ (2002) J Comput Chem 23:554–563

    Article  Google Scholar 

  58. Luque FJ, Barril X, Orozco M (1999) J Comput Aided Mol Des 13:139–152

    Article  CAS  Google Scholar 

  59. Curutchet C, Orozco M, Luque FJ (2001) J Comput Chem 22:1180–1193

    Article  CAS  Google Scholar 

  60. Luque FJ, Curutchet C, Muñoz-Muriedas J, Bidon-Chanal A, Morreale A, Gelpi JL, Orozco M (2003) Phys Chem Chem Phys 5:3827–3836

    Article  Google Scholar 

  61. Miertus S, Scrocco E, Tomasi J (1981) Chem Phys 55:117–129

    Article  CAS  Google Scholar 

  62. Pierotti RA (1976) Chem Rev 76:717–726

    Article  CAS  Google Scholar 

  63. Claverie P (1978) In: Pullman B (ed) Intermolecular interactions: from diatomics to biomolecules. Wiley, Chichester

    Google Scholar 

  64. Luque FJ, Bofill JM, Orozco M (1995) J Chem Phys 103:10183–10191

    Article  CAS  Google Scholar 

  65. Orozco M, Bachs M, Luque FJ (1995) J Comput Chem 16:563–575

    Article  CAS  Google Scholar 

  66. Peterson M, Poirier, R MonsterGauss. Department of Biochemistry, Univ Toronto, Canada. Version modified by Cammi R, Tomasi J (1987) and by Curutchet C, Orozco M, Luque FJ (2004)

  67. Huertas O, Orozco M, Luque FJ (2006) J Phys Chem A 110:510–518

    Article  CAS  Google Scholar 

  68. Hobza P, Sponer J (1999) Chem Rev 99:3247–3276

    Article  CAS  Google Scholar 

  69. Bader RFW (1991) Chem Rev 91:893–928

    Article  CAS  Google Scholar 

  70. Silvi B, Savin A (1994) Nature 31:683–686

    Article  Google Scholar 

  71. Alkorta I, Rozas I, Elguero J (1998) Struct Chem 9:243–248

    Article  CAS  Google Scholar 

  72. Muñoz J, Sponer J, Hobza P, Orozco M, Luque FJ (2001) J Phys Chem B 105:6051–6060

    Article  Google Scholar 

  73. Fuster F, Silvi B (2000) Theor Chem Acc 104:13–21

    CAS  Google Scholar 

  74. Orozco M, Cubero E, Barril X, Colominas C, Luque FJ (1999) Nucleic acid bases in solution. In: Leszczynski J (ed) Computational molecular biology. Theoretical computational chemistry, vol 8 Elsevier, Amsterdam, pp 119–165

    Google Scholar 

  75. Wu Y, Ogawa AK, Berger M, McMinn DL, Schuitz PG, Romesberg FE (2000) J Am Chem Soc 122:7621–7632

    Article  CAS  Google Scholar 

  76. Loakes D (2001) Nucleic Acids Res 29:2437–2447

    Article  CAS  Google Scholar 

  77. Hansch C, Leo A (1995) Exploring QSAR: hydrophobic, electronic and steric constants. American Chemical Society, Washington

    Google Scholar 

Download references

Acknowledgments

We thank the Ministerio de Ciencia y Tecnología (grants CTQ2005-09365 and BIO2003-06848) for financial assistance and the Centre de Supercomputació de Catalunya for computational facilities.

Author information

Authors and Affiliations

  1. Departament de Fisicoquímica, Facultat de Farmàcia, Avgda. Diagonal 643, Barcelona, 08028, Spain

    Jordi Muñoz-Muriedas, José María López & Francisco Javier Luque

  2. ICREA and Departament de Fisicoquímica, Facultat de Farmàcia, Avgda. Diagonal 643, Barcelona, 08028, Spain

    Xavier Barril

  3. Departament de Bioquímica i Biología Molecular, Facultat de Química, Universitat de Barcelona, Martí i Franqués 1, Barcelona, 08028, Spain

    Modesto Orozco

  4. Unitat de Modelització Molecular i Bioinformàtica, Parc Científic de Barcelona, Josep Samitier 1-6, Barcelona, 08028, Spain

    Modesto Orozco

Authors
  1. Jordi Muñoz-Muriedas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xavier Barril
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. José María López
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Modesto Orozco
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francisco Javier Luque
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Modesto Orozco or Francisco Javier Luque.

Additional information

Proceedings of “Modeling Interactions in Biomolecules II”, Prague, September 5th–9th, 2005.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Muñoz-Muriedas, J., Barril, X., López, J.M. et al. A hydrophobic similarity analysis of solvation effects on nucleic acid bases. J Mol Model 13, 357–365 (2007). https://doi.org/10.1007/s00894-006-0150-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00894-006-0150-y

Keywords

Search

Navigation