Advertisement

European Biophysics Journal

, Volume 15, Issue 1, pp 13–26 | Cite as

Molecular mechanics calculations of dA12·dT12 and of the curved molecule d(GCTCGAAAAA)4·d(TTTTTCGAGC)4

  • E. von Kitzing
  • S. Diekmann
Article

Abstract

Using the AMBER software package (Weiner and Kollman 1981) substantially modified for electrostatic contributions, the structural energies of the double-stranded oligonucleotides dA12·dT12 and d(GCTCGAAAAA)4·d(TTTTTCGAGC)4 were minimized. Using various starting structures for the molecule dA12·dT12, one final structure is obtained which possesses the experimentally determined properties of poly(dA)·poly(dT). This structure is an A-form-B-form-hybrid structure similar to that of Arnott et al. (1983). The dA-strand is similar to an A-form while the dT-strand is similar to normal B-form. This structure and separately optimized B-form sequence stretches were used to construct the double-stranded fragment d(GCTCGAAAAA)4 which again was optimized. This sequence, when imbedded in a DNA fragment as contiguous repeats, shows a gel migration anomaly which has been interpreted as stable curvature of the DNA (Diekmann 1986). The calculated structure of this sequence indeed has a curved helix axis and is discussed as a model for curved DNA. A theoretical formalism is presented which allows one to calculate the structural parameters of any nucleic acid double helix in two different geometrical representations. This formalism is used to determine the parameters of the base-pair orientations of the curved structure in terms of wedge as well as cylindrical parameters. In the structural model presented here, the curvature of the helix axis results from an alternation of two different DNA structures in which the base-pairs possess different angles with the helix axis (‘cylinder tilt’). Resulting from geometric restraints, a negative cylinder tilt angle correlates strongly with the closing of the minor groove (‘wedge roll’). The blocks with different structure are not exactly coincident with the dA5-blocks and the B-DNA stretches. Within the dA5 block, base-pair tilt and wedge roll adopt large values which proceed into the 3′ flanking B-DNA sequence by about one base-pair. These properties of the structure calculated here are discussed in terms of different models explaining DNA curvature.

Key words

Molecular mechanics symmetry constraints structure parameters of DNA poly(dA) · poly(dT) DNA curvature 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arnott S, Hukins DWL (1972) Optimized parameters for A-DNA and B-DNA. Biochem Biophys Res Commun 47: 1504–1510Google Scholar
  2. Arnott S, Dover SD, Wonacott AJ (1969) Least-squares refinement of the crystal and molecular structure of DNA and RNA from X-ray data and bond length and angles. Acta Crystallogr B 25:2192–2206Google Scholar
  3. Arnott S, Chandrasekaran R, Hall IH, Puigjaner LC (1983) Heteronomous DNA. Nucl Acid Res 11:4141–4151Google Scholar
  4. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) CHARMM: A program for macromolecular energy, minimization and dynamics calculations. J Comp Chem 4:187–217Google Scholar
  5. Bubienko E, Cruz P, Thomason JF, Borer PN (1983) Nearestneighbour effects in the structure and function of nucleic acids. Prog Nucl Acids Res Mol Biol 30:41–90Google Scholar
  6. Dickerson RE (1983) Base sequence and helix structure variation in B- and A-DNA. J Mol Biol 166:419–441Google Scholar
  7. Diekmann S (1986) Sequence specificity of curved DNA. FEBS Lett 195:53–56Google Scholar
  8. Diekmann S (1987a) Temperature and salt dependence of the migration anomaly of curved DNA fragments. Nucl Acids Res 15:247–265Google Scholar
  9. Diekmann S (1987b) DNA curvature. In: Eckstein F, Lilley DM (eds) Nucleic acids and molecular biology, vol 1. Springer, Berlin Heidelberg New YorkGoogle Scholar
  10. Diekmann S, Wang JC (1985) On the sequence determinants and flexibility of the kinetoplast DNA fragment with abnormal gel electrophoretic mobilities. J Mol Biol 186: 1–11Google Scholar
  11. Drew HR, Travers AA (1985) DNA bending and its relation to nucleosome positioning. J Mol Biol 186:773–790Google Scholar
  12. Edmondson SP, Johnson WC (1985) Base tilt of poly(dA) · poly(dT) and poly(dAT) · poly(dAT) in solution determined by linear dichroism. Biopolymers 24:825–841Google Scholar
  13. Fratini AV, Kopka ML, Drew HR, Dickerson RE (1982) Reversible bending and helix geometry in a B-DNA dodecamer: CGCGAATT(Br)CGCG. J Biol Chem 257: 14686–14707Google Scholar
  14. Griffith J, Bleyman M, Rauch CA, Kitchin PA, Englund PT (1986) Visualization of the bent helix in kinetoplast DNA by electron microscopy. Cell 46:717–724Google Scholar
  15. Hagerman PJ (1984) Evidence for the existence of stable curvature of DNA in solution. Proc Natl Acad Sci USA 81:4632–4636Google Scholar
  16. Hagerman PJ (1985) Sequence dependence of the curvature of DNA: a test of the phasing hypothesis. Biochemistry 24: 7033–7037Google Scholar
  17. Hagerman PJ (1986) Sequence-directed curvature of DNA. Nature 321:449–450Google Scholar
  18. Haran TE, Berkovich Z, Shakked Z (1984) Base-stacking interactions in double-helical DNA structures: experiment versus theory. J Biomol Struct Dyn 2:397–412Google Scholar
  19. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN) (1983) In: Pullman B, Jortner J (eds) Nucleic acids: the vectors of life. Reidel, Dordrecht, pp 559–565Google Scholar
  20. Jolles B, Laigle A, Chinsky L, Turpin PY (1985) The poly(dA) strand of poly(dA) · poly(dT) adopts an A-form in solution: a UV resonance Raman study. Nucl Acid Res 13: 2075–2085Google Scholar
  21. Katahira M, Nishimura Y, Tsuboi M, Sato T, Mitsui Y, Iitaka Y (1986) Local and overall conformations of DNA double helices with the A · T base pairs. Biochim Biophys Acta 867:256–267Google Scholar
  22. Kitzing Ev (1986) Molekülsimulation mit Hilfe von Kraftfeld-rechnungen am Beispiel der Aggregation von Nukleinsäuren verschiedener Konformation zu einem Komplex mit Übersetzungsfunktion. Edition Herodot/Rader, AachenGoogle Scholar
  23. Klement R, Kitzing Ev, Jovin T, Soumpasis DM (1985) Molecular mechanical simulations of the DNA B-Z transition compared to the RNA A-Z transition. In: Sarma RH (ed) Book of abstracts, 4th Conversation in Biomolecular Stereodynamics. Adenine Press, New YorkGoogle Scholar
  24. Koo HS, Wu HM, Crother DM (1986) DNA bending at adenine-thymine tracts. Nature 320:501–506Google Scholar
  25. Kunkel GR, Martinson HG (1981) Nucleosomes will not form on double-stranded RNA or over poly(dA) · poly(dT) tracts in recombinant DNA. Nucl Acid Res 9:6869–6888Google Scholar
  26. Levene SD, Crothers DM (1983) A computer graphics study of sequence-directed bending in DNA. J Biomol Struct Dyn 1:429–435Google Scholar
  27. Levitt M (1983) Protein folding by restrained energy minimization and molecular dynamics. J Mol Biol 170: 723–764Google Scholar
  28. Marini JC, Levene SD, Crothers DM, Englund PT (1982) Bent helical structure in kinetoplast DNA. Proc Natl Acad Sci USA 79:7664–7668Google Scholar
  29. Marini JC, Englund PT (1983) Correction. Proc Natl Acad Sci USA 80:7678Google Scholar
  30. Peck LJ, Wang JC (1981) Sequence dependence of the helical repeat of DNA in solution. Nature 292:375–378Google Scholar
  31. Premilat S, Albiser G (1984) Conformation of C-DNA in agreement with fiber X-ray and infrared dichroism. J Biomol Struct Dyn 3:607–613Google Scholar
  32. Prunell A (1982) Nucleosome reconstitution on plasmid inserted poly(dA) · poly(dT). EMBO J 1:173–179Google Scholar
  33. Prunell A, Goulet I, Jacob Y, Goutorbe J (1984) The smaller helical repeat of poly(dA) · poly(dT) relative to DNA may reflect the wedge property of the dA · dT base pair. Eur J Biochem 138:253–257Google Scholar
  34. Rao SN, Kollman PA (1985) On the role of uniform and mixed sugar puckers in DNA double-helical structures. J Am Chem Soc 107:1611–1617Google Scholar
  35. Remerie K, Gunstere WF van, Engberts JBFN (1985) Molecular dynamics computer simulation as a tool for analysis of solvation. A study of dilute aqueous solution of 1,4- and 1,3-dioxan. Recl Trav Chim Pays-Bas 104:79–89Google Scholar
  36. Rhodes D (1979) Nucleosome cores reconstituted from poly(dA-dT) and the octamer of histones. Nucl Acid Res 6:1805–1816Google Scholar
  37. Rhodes D, Klug A (1981) Sequence-dependent helical periodicity of DNA. Nature 292:378–380Google Scholar
  38. Sarma MH, Gupta G, Sarma RH (1985) Untentability of the heteronomous DNA-model for dAn · dTn in solution. J Biomol Struct Dyn 2:1057–1084Google Scholar
  39. Sasisekharan V, Bansal M, Gupta G (1983) Structures of DNA: a case study of right and left handed Duplex in the B-form. In: Pullman B, Jortner J (eds) Nucleic acids: the vectors of life. Reidel, Dordrecht, pp 101–111Google Scholar
  40. Selsing E, Wells RD, Alden CJ, Arnott S (1979) Bent DNA: visualization of a base-paired and stacked A-B conformational junction. J Biol Chem 254:5417–5422Google Scholar
  41. Shanno DF (1978) On the convergence of a new conjugate gradient algorithm. SIAM J Numer Anal 15:1247–1252Google Scholar
  42. Simpson RT, Kunzler P (1979) Chromatin and core particles formed from the inner histones and synthetic polydeoxyribonucleotides of defined sequence. Nucl Acid Res 6: 1387–1415Google Scholar
  43. Singh UC, Weiner SJ, Kollman P (1985) Molecular dynamics simulations of d(CGCGA) · d(TCGCG) with and without hydrated counter ions. Proc Natl Acad Sci USA 82: 755–759Google Scholar
  44. Soumpasis MD (1984) Statistical mechanics of B-Z-transition of DNA: Contribution of diffuse ionic interaction. Proc Natl Acad Sci USA 81:5116–5120Google Scholar
  45. Strauss F, Gaillard C, Prunell A (1981) Helical periodicity of DNA, poly(dA) · poly(dT), and poly(dA-dT) · poly(dA-dT) in solution. Eur J Biochem 118:215–222Google Scholar
  46. Thomas GA, Peticolas WL (1983) Fluctuations in nucleic acid conformations. 2. Raman spectroscopic evidence of varying ring pucker in A-T polynucleotides. J Am Chem Soc 105:993–996Google Scholar
  47. Trifonov EN (1985) Curved DNA. CRC Crit Rev Biochem 19:89–106Google Scholar
  48. Trifonov EN, Sussman JL (1980) The pitch of chromatin DNA is reflected in its nucleotide sequence. Proc Natl Acad Sci USA 77:3816–3820Google Scholar
  49. Tung CS, Harvey SC (1986) Base sequence, local helix structure, and macroscopic curvature of A-DNA and B-DNA. J Biol Chem 261:3700–3709Google Scholar
  50. Ulanovsky L, Trifonov EN (1987) Estimation of wedge components in curved DNA. Nature 326:720–722Google Scholar
  51. Ulanovsky L, Bodner M, Trifonov EN, Choder M (1986) Curved DNA: design, synthesis, and circularization. Proc Natl Acad Sci USA 83:862–866Google Scholar
  52. Warshel A, Levitt M (1976) Theoretical studies of enzymatic reactions. J Mol Biol 103:227–249PubMedGoogle Scholar
  53. Wartell RM, Harrell JT (1986) Characteristics and variations of B-type DNA conformations in solution: a quantitative analysis of Raman band intensities of eight DNAs. Biochemistry 25:2664–2671Google Scholar
  54. Weiner PK, Kollman PA (1981) AMBER. Assisted model building with energy refinement. J Comput Chem 2: 287–303Google Scholar
  55. Weiner JS, Kollman PA, Case DA, Singh UC, Ohio C, Alogerma G, Profeta jr S, Weiner PK (1984) A new force field for molecular mechanical simulations of nucleic acids and proteins. J Am Chem Soc 106:765–784Google Scholar
  56. Wu HM, Crothers DM (1984) The locus of sequence-directed and protein-induced DNA bending. Nature 308:509–513Google Scholar
  57. Zhurkin VB (1985) Sequence-dependent bending of DNA and phasing of nucleosomes. J Biomol Struct Dyn 2:785–804Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • E. von Kitzing
    • 1
  • S. Diekmann
    • 1
  1. 1.Max-Planck-Institut für Biophysikalische ChemieGöttingen-NikolausbergFederal Republic of Germany

Personalised recommendations