Biologically important conformational features of DNA as interpreted by quantum mechanics and molecular mechanics computations of its simple fragments

  • V. PoltevEmail author
  • V. M. Anisimov
  • V. Dominguez
  • E. Gonzalez
  • A. Deriabina
  • D. Garcia
  • F. Rivas
  • N. A. Polteva
Original Paper
Part of the following topical collections:
  1. QUITEL 2016


Deciphering the mechanism of functioning of DNA as the carrier of genetic information requires identifying inherent factors determining its structure and function. Following this path, our previous DFT studies attributed the origin of unique conformational characteristics of right-handed Watson-Crick duplexes (WCDs) to the conformational profile of deoxydinucleoside monophosphates (dDMPs) serving as the minimal repeating units of DNA strand. According to those findings, the directionality of the sugar-phosphate chain and the characteristic ranges of dihedral angles of energy minima combined with the geometric differences between purines and pyrimidines determine the dependence on base sequence of the three-dimensional (3D) structure of WCDs. This work extends our computational study to complementary deoxydinucleotide-monophosphates (cdDMPs) of non-standard conformation, including those of Z-family, Hoogsteen duplexes, parallel-stranded structures, and duplexes with mispaired bases. For most of these systems, except Z-conformation, computations closely reproduce experimental data within the tolerance of characteristic limits of dihedral parameters for each conformation family. Computation of cdDMPs with Z-conformation reveals that their experimental structures do not correspond to the internal energy minimum. This finding establishes the leading role of external factors in formation of the Z-conformation. Energy minima of cdDMPs of non-Watson-Crick duplexes demonstrate different sequence-dependence features than those known for WCDs. The obtained results provide evidence that the biologically important regularities of 3D structure distinguish WCDs from duplexes having non-Watson-Crick nucleotide pairing.


Conformation of biopolymers Sequence dependence Density functional theory Molecular mechanics Quantum mechanics computations 



The authors thankfully acknowledge computer resources, technical advice and support provided by Laboratorio Nacional de Supercomputo del Sureste de Mexico (LNS), a member of the CONACYT national laboratories.

Supplementary material

894_2018_3589_MOESM1_ESM.pdf (464 kb)
ESM 1 (PDF 463 kb)


  1. 1.
    Watson JD, Crick FHC (1953a) Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid. Nature 171:737–738CrossRefGoogle Scholar
  2. 2.
    Watson JD, Crick FHC (1953b) Genetical implications of the structure of deoxyribonucleic acid. Nature 171:964–967CrossRefGoogle Scholar
  3. 3.
    Berman HM, Olson WK, Beveridge DL, Westbrook J, Gelbin A, Demeny T, Hsieh S-H, Srinivasan AR, Schneider B (1992) A comprehensive relational database of three-dimensional structures of nucleic acids. Biophys J 63:751–759CrossRefGoogle Scholar
  4. 4.
    Svozil D, Kalina J, Omelka M, Schneider B (2008) DNA conformations and their sequence preferences. Nucleic Acids Res 36:3690–3706CrossRefGoogle Scholar
  5. 5.
    Čech P, Kukal J, Černý J, Schneider B, Svozil D (2013) Automatic workflow for the classification of local DNA conformations. BMC Bioinformatics 14:205CrossRefGoogle Scholar
  6. 6.
    Šponer J, Mládek A, Šponer JE, Svozil D, Zgarbová M, Banáš P, Jurečka P, Otyepka M (2012) The DNA and RNA sugar-phosphate backbone emerges as the key player. An overview of quantum-chemical, structural biology and simulation studies. Phys Chem Chem Phys 14:15257–15277CrossRefGoogle Scholar
  7. 7.
    Zgarbová M, Šponer J, Otyepka M, Cheatham TE, Galindo-Murillo R, Jurečka P (2015) Refinement of the sugar-phosphate backbone torsion beta for AMBER force fields improves the description of Z- and B-DNA. J Chem Theory Comput 11:5723–5736CrossRefGoogle Scholar
  8. 8.
    Ivani I et al (2016) Parmbsc1: a refined force field for DNA simulations. Nat Methods 13:55–58CrossRefGoogle Scholar
  9. 9.
    Galindo-Murillo R, Robertson JC, Marie Zgarbova M, Šponer J, Otyepka M, Jurečka P, Cheatham TE (2016) Assessing the current state of amber force field modifications for DNA. J Chem Theory Comput 2016(12):4114–4127CrossRefGoogle Scholar
  10. 10.
    Zhang Y-C et al (2012) Theoretical study on steric effects of DNA phosphorothioation: B-helical destabilization in Rp-phosphorothioated DNA. J Phys Chem B 116:10639–10648CrossRefGoogle Scholar
  11. 11.
    Kruse H, Mladek A, Gkionis K, Andreas Hansen A, Grimme S, Sponer J (2015) Quantum chemical benchmark study on 46 RNA backbone families using a dinucleotide unit. J Chem Theory Comput 11:4972–4991CrossRefGoogle Scholar
  12. 12.
    Poltev VI, Anisimov VM, Danilov VI, Deriabina A, Gonzalez E, Jurkiewiez A, Les A, Polteva N (2007) DFT study of B-like conformations of deoxydinucleoside monophosphates. J Biomol Struct Dyn 24:660Google Scholar
  13. 13.
    Poltev VI, Anisimov VM, Danilov VI, Deriabina A, Gonzalez E, Jurkiewiez A, Les A, Polteva N (2008) DFT study of B-like conformations of deoxydinucleoside monophosphates containing Gua and/or Cyt and their complexes with Na+ cation. J Biomol Struct Dyn 25:563–571CrossRefGoogle Scholar
  14. 14.
    Poltev VI, Anisimov VM, Danilov VI, Deriabina A, Gonzalez E, Garcia D, Rivas F, Jurkievich A, Les A, Polteva N (2009) DFT study of minimal fragments of nucleic acid single chain for explication of sequence dependence of DNA duplex conformation. J Mol Struct THEOCHEM 912:53–59CrossRefGoogle Scholar
  15. 15.
    Poltev VI, Anisimov VM, Danilov VI, Van Mourik T, Deriabina A, Gonzalez E, Padua M, Garcia D, Rivas F, Polteva N (2010) DFT study of polymorphism of the DNA double helix at the level of dinucleoside monophosphates. Int J Quantum Chem 110:2548–2559CrossRefGoogle Scholar
  16. 16.
    Poltev VI, Anisimov VM, Danilov VI, Garcia D, Deriabina A, Gonzalez E, Salazar R, Rivas F, Polteva N (2011) DFT study of DNA sequence dependence at the level of dinucleoside monophosphates. Comput Theoret Chem 975:69–75CrossRefGoogle Scholar
  17. 17.
    Poltev V, Anisimov VM, Danilov VI, Garcia D, Sanchez C, Deriabina A, Gonzalez E, Salazar R, Rivas F, Polteva N (2014) The role of molecular structure of sugar-phosphate backbone and nucleic acid bases in the formation of single-stranded and double-stranded DNA structures. Biopolymers 101:640–650CrossRefGoogle Scholar
  18. 18.
    Poltev VI, Anisimov VM, Sanchez C, Deriabina A, Gonzalez E, Garcia D, Rivas F, Polteva NA (2016) Analysis of the conformational features of Watson–crick duplex fragments by molecular mechanics and quantum mechanics methods. Biophysics 61:217–226CrossRefGoogle Scholar
  19. 19.
    Churchill CDM, Wetmore SD (2011) Developing a computational model that accurately reproduces the structural features of a dinucleoside monophosphate unit within B-DNA. Phys Chem Chem Phys 13:16373–16383CrossRefGoogle Scholar
  20. 20.
    Smith DA, Holroyd LF, van Mourik T, Jones AC (2016) A DFT study of 2-aminopurine-containing dinucleotides: prediction of stacked conformations with B-DNA structure. Phys Chem Chem Phys 18:14691–14700CrossRefGoogle Scholar
  21. 21.
    Zubatiuk TA, Shishkin OV, Gorb L, Hovorun DM, Leszczynski J (2013) B-DNA characteristics are preserved in double stranded d(a)3:d(T)3 and d(G)3:d(C)3 mini-helixes: conclusions from DFT/M06-2X study. Phys Chem Chem Phys 15:18155–18166CrossRefGoogle Scholar
  22. 22.
    Zubatiuk TA, Kukuev MA, Korolyova AS, Gorb L, Nyporko A, Hovorun D, Leszczynski J (2015) Structure and binding energy of double-stranded A-DNA minihelices:quantum-chemical study. J Phys Chem B 119:12741–12749CrossRefGoogle Scholar
  23. 23.
    Case DA, Betz RM, Botello-Smith W et al (2016) AMBER 2016. University of California, San FranciscoGoogle Scholar
  24. 24.
    Frisch MJ, Trucks GW, Schlegel HB et al (2009) Gaussian 09, Revision D.01. Gaussian, Inc., WallingfordGoogle Scholar
  25. 25.
    Perdew JP, Burke K, Ernzerhof M (1996) Generalized gradient approximation made simple. Phys Rev Lett 77:3865–3868CrossRefGoogle Scholar
  26. 26.
    te Velde G, Bickelhaupt FM, Baerends EJ, Fonseca GC, van Gisbergen SJA, Snijders JG, Ziegler T (2001) Chemistry with ADF. J Comp Chem 22:931–967CrossRefGoogle Scholar
  27. 27.
    Zheng G, Lu X-J, Olson WK (2009) Web 3DNA - a web server for the analysis, reconstruction, and visualization of three dimensional nucleic-acid structures. Nucleic Acids Res 37:W240–W246CrossRefGoogle Scholar
  28. 28.
    Zhao Y, Truhlar DG (2011) Applications and validations of the Minnesota density functionals. Chem Phys Let 502:1–13CrossRefGoogle Scholar
  29. 29.
    Klamt A, Schüürmann G (1993) COSMO: a new approach to dielectric screening in solvents with explicit expressions for the screening energy and its gradient. J Chem Soc Perkin Trans 2:799CrossRefGoogle Scholar
  30. 30.
    Wong MW, Wiberg KB, Frisch MJ (1992) Solvent effects. 2. Medium effect on the structure, energy, charge density, and vibrational frequencies of sulfamic acid. J Am Chem Soc 114:523–529CrossRefGoogle Scholar
  31. 31.
    Tomasi J, Mennucci B, Cammi R (2005) Quantum mechanical continuum solvation models. Chem Rev 105:2999–3093CrossRefGoogle Scholar
  32. 32.
    Grimme S, Ehrlich S, Goerigk L (2011) Effect of the damping function in dispersion corrected density functional theory. J Comp Chem 32:1456–1465CrossRefGoogle Scholar
  33. 33.
    Girard E, Prange T, Dhaussy AC, Migianu-Griffoni E, Lecouvey M, Chervin JC, Mezouar M, Kahn R, Fourme R (2007) Adaptation of the base-paired double-helix molecular architecture to extreme pressure. Nucleic Acids Res 35:4800–4808CrossRefGoogle Scholar
  34. 34.
    Wang AHJ, Quigley GJ, Kolpak FJ, Crawford JL, van Boom JH, Van der Marel G, Rich A (1979) Molecular structure of a left-handed double helical DNA fragment at atomic resolution. Nature 282:680–686CrossRefGoogle Scholar
  35. 35.
    Brzezinski K, Brzuszkiewicz A, Dauter M, Kubicki M, Jaskolski M, Dauter Z (2011) High regularity of Z-DNA revealed by ultra high-resolution crystal structure at 0.55 Å. Nucleic Acids Res 39:6238–6248CrossRefGoogle Scholar
  36. 36.
    Hoogsteen K (1959) The structure of crystals containing a hydrogen-bonded complex of 1-methylthymine and 9-methyladenine. Acta Crystallogr 12:822–823CrossRefGoogle Scholar
  37. 37.
    Frank-Kamenetskii MD, Mirkin SM (1995) Triplex DNA structures. Annu Rev Biochem 64:65–95CrossRefGoogle Scholar
  38. 38.
    Abrescia NGA, Gonzalez C, Gouyette C, Subirana JA (2004) X-ray and NMR studies of the DNA oligomer d(ATATAT): Hoogsteen base pairing in duplex DNA. Biochemistry 43:4092–4100CrossRefGoogle Scholar
  39. 39.
    Acosta-Reyes FJ, Alechaga E, Subirana JA, Campos JL (2015) Structure of the DNA duplex d(ATTAAT)2 with hoogsteen hydrogen bonds. PLoS One 10(3):e0120241CrossRefGoogle Scholar
  40. 40.
    Parvathy VR, Bhaumik SR, Chary KV, Govil G, Liu K, Howard FB, Miles HT (2002) NMR structure of a parallel-stranded DNA duplex at atomic resolution. Nucleic Acids Res 30:1500–1511CrossRefGoogle Scholar
  41. 41.
    Hunter WN, Brown T, Kneale G, Anand NN, Rabinovich D, Kennard O (1987a) The structure of guanosine-thymidine mismatches in B-DNA at 2.5-Å resolution. J Biol Chem 262:9962–9970Google Scholar
  42. 42.
    Brown T, Hunter WN, Kneale G, Kennard O (1986) Molecular structure of the GA base pair in DNA and its implications for the mechanism of transversion mutations. Proc Natl Acad Sci USA 83:2402–2406CrossRefGoogle Scholar
  43. 43.
    Hunter WN, Brown T, Robinson P, Kennard O (1987b) Inosine-adenine base pairs in a B-DNA duplex. Nucleic Acids Res 15:7935–7949CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Autonomous University of PueblaPueblaMexico
  2. 2.National Center for Supercomputing ApplicationsUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  3. 3.Institute of Theoretical and Experimental BiophysicsRussian Academy of SciencesPushchinoRussia

Personalised recommendations