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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Dec;83(24):9373–9377. doi: 10.1073/pnas.83.24.9373

Improved free-energy parameters for predictions of RNA duplex stability.

S M Freier, R Kierzek, J A Jaeger, N Sugimoto, M H Caruthers, T Neilson, D H Turner
PMCID: PMC387140  PMID: 2432595

Abstract

Thermodynamic parameters for prediction of RNA duplex stability are reported. One parameter for duplex initiation and 10 parameters for helix propagation are derived from enthalpy and free-energy changes for helix formation by 45 RNA oligonucleotide duplexes. The oligomer sequences were chosen to maximize reliability of secondary structure predictions. Each of the 10 nearest-neighbor sequences is well-represented among the 45 oligonucleotides, and the sequences were chosen to minimize experimental errors in delta GO at 37 degrees C. These parameters predict melting temperatures of most oligonucleotide duplexes within 5 degrees C. This is about as good as can be expected from the nearest-neighbor model. Free-energy changes for helix propagation at dangling ends, terminal mismatches, and internal G X U mismatches, and free-energy changes for helix initiation at hairpin loops, internal loops, or internal bulges are also tabulated.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albergo D. D., Marky L. A., Breslauer K. J., Turner D. H. Thermodynamics of (dG--dC)3 double-helix formation in water and deuterium oxide. Biochemistry. 1981 Mar 17;20(6):1409–1413. doi: 10.1021/bi00509a001. [DOI] [PubMed] [Google Scholar]
  2. Appleby D. W., Kallenbach N. R. Theory of oligonucleotide stabilization. I. The effect of single-strand stacking. Biopolymers. 1973;12(9):2093–2120. doi: 10.1002/bip.1973.360120915. [DOI] [PubMed] [Google Scholar]
  3. Auron P. E., Rindone W. P., Vary C. P., Celentano J. J., Vournakis J. N. Computer-aided prediction of RNA secondary structures. Nucleic Acids Res. 1982 Jan 11;10(1):403–419. doi: 10.1093/nar/10.1.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Borer P. N., Dengler B., Tinoco I., Jr, Uhlenbeck O. C. Stability of ribonucleic acid double-stranded helices. J Mol Biol. 1974 Jul 15;86(4):843–853. doi: 10.1016/0022-2836(74)90357-x. [DOI] [PubMed] [Google Scholar]
  5. Breslauer K. J., Sturtevant J. M., Tinoco I., Jr Calorimetric and spectroscopic investigation of the helix-to-coil transition of a ribo-oligonucleotide: rA7U7. J Mol Biol. 1975 Dec 25;99(4):549–565. doi: 10.1016/s0022-2836(75)80171-9. [DOI] [PubMed] [Google Scholar]
  6. Cech T. R., Tanner N. K., Tinoco I., Jr, Weir B. R., Zuker M., Perlman P. S. Secondary structure of the Tetrahymena ribosomal RNA intervening sequence: structural homology with fungal mitochondrial intervening sequences. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3903–3907. doi: 10.1073/pnas.80.13.3903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Coutts S. M., Gangloff J., Dirheimer G. Conformational transitions in tRNA Asp (brewer's yeast). Thermodynamic, kinetic, and enzymatic measurements on oligonucleotide fragments and the intact molecule. Biochemistry. 1974 Sep 10;13(19):3938–3948. doi: 10.1021/bi00716a019. [DOI] [PubMed] [Google Scholar]
  8. Craig M. E., Crothers D. M., Doty P. Relaxation kinetics of dimer formation by self complementary oligonucleotides. J Mol Biol. 1971 Dec 14;62(2):383–401. doi: 10.1016/0022-2836(71)90434-7. [DOI] [PubMed] [Google Scholar]
  9. Fink T. R., Crothers D. M. Free energy of imperfect nucleic acid helices. I. The bulge defect. J Mol Biol. 1972 Apr 28;66(1):1–12. doi: 10.1016/s0022-2836(72)80002-0. [DOI] [PubMed] [Google Scholar]
  10. Freier S. M., Alkema D., Sinclair A., Neilson T., Turner D. H. Contributions of dangling end stacking and terminal base-pair formation to the stabilities of XGGCCp, XCCGGp, XGGCCYp, and XCCGGYp helixes. Biochemistry. 1985 Aug 13;24(17):4533–4539. doi: 10.1021/bi00338a008. [DOI] [PubMed] [Google Scholar]
  11. Freier S. M., Kierzek R., Caruthers M. H., Neilson T., Turner D. H. Free energy contributions of G.U and other terminal mismatches to helix stability. Biochemistry. 1986 Jun 3;25(11):3209–3213. doi: 10.1021/bi00359a019. [DOI] [PubMed] [Google Scholar]
  12. Freier S. M., Petersheim M., Hickey D. R., Turner D. H. Thermodynamic studies of RNA stability. J Biomol Struct Dyn. 1984 Mar;1(5):1229–1242. doi: 10.1080/07391102.1984.10507514. [DOI] [PubMed] [Google Scholar]
  13. Freier S. M., Sinclair A., Neilson T., Turner D. H. Improved free energies for G.C base-pairs. J Mol Biol. 1985 Oct 5;185(3):645–647. doi: 10.1016/0022-2836(85)90077-4. [DOI] [PubMed] [Google Scholar]
  14. Freier S. M., Sugimoto N., Sinclair A., Alkema D., Neilson T., Kierzek R., Caruthers M. H., Turner D. H. Stability of XGCGCp, GCGCYp, and XGCGCYp helixes: an empirical estimate of the energetics of hydrogen bonds in nucleic acids. Biochemistry. 1986 Jun 3;25(11):3214–3219. doi: 10.1021/bi00359a020. [DOI] [PubMed] [Google Scholar]
  15. Gralla J., Crothers D. M. Free energy of imperfect nucleic acid helices. 3. Small internal loops resulting from mismatches. J Mol Biol. 1973 Aug 5;78(2):301–319. doi: 10.1016/0022-2836(73)90118-6. [DOI] [PubMed] [Google Scholar]
  16. Gralla J., Crothers D. M. Free energy of imperfect nucleic acid helices. II. Small hairpin loops. J Mol Biol. 1973 Feb 5;73(4):497–511. doi: 10.1016/0022-2836(73)90096-x. [DOI] [PubMed] [Google Scholar]
  17. Hickey D. R., Turner D. H. Solvent effects on the stability of A7U7p. Biochemistry. 1985 Apr 9;24(8):2086–2094. doi: 10.1021/bi00329a042. [DOI] [PubMed] [Google Scholar]
  18. Jacobson A. B., Good L., Simonetti J., Zuker M. Some simple computational methods to improve the folding of large RNAs. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):45–52. doi: 10.1093/nar/12.1part1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Neilson T., Romaniuk P. J., Alkema D., Hughes D. W., Everett J. R., Bell R. A. The effects of base sequence and dangling bases on the stability of short ribonucleic acid duplexes. Nucleic Acids Symp Ser. 1980;(7):293–311. [PubMed] [Google Scholar]
  20. Nelson J. W., Martin F. H., Tinoco I., Jr DNA and RNA oligomer thermodynamics: the effect of mismatched bases on double-helix stability. Biopolymers. 1981 Dec;20(12):2509–2531. doi: 10.1002/bip.1981.360201204. [DOI] [PubMed] [Google Scholar]
  21. Nussinov R., Tinoco I., Jr, Jacobson A. B. Small changes in free energy assignments for unpaired bases do not affect predicted secondary structures in single stranded RNA. Nucleic Acids Res. 1982 Jan 11;10(1):341–349. doi: 10.1093/nar/10.1.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Papanicolaou C., Gouy M., Ninio J. An energy model that predicts the correct folding of both the tRNA and the 5S RNA molecules. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):31–44. doi: 10.1093/nar/12.1part1.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Petersheim M., Turner D. H. Base-stacking and base-pairing contributions to helix stability: thermodynamics of double-helix formation with CCGG, CCGGp, CCGGAp, ACCGGp, CCGGUp, and ACCGGUp. Biochemistry. 1983 Jan 18;22(2):256–263. doi: 10.1021/bi00271a004. [DOI] [PubMed] [Google Scholar]
  24. Riesner D., Maass G., Thiebe R., Philippsen P., Zachau H. G. The conformational transitions in yeast tRNAPhe as studied with tRNAPhe fragments. Eur J Biochem. 1973 Jul 2;36(1):76–88. doi: 10.1111/j.1432-1033.1973.tb02887.x. [DOI] [PubMed] [Google Scholar]
  25. Ross P. D., Scruggs R. L. Heat of the reaction forming the three-stranded poly (A + 2U) complex. Biopolymers. 1965;3(4):491–496. doi: 10.1002/bip.1965.360030410. [DOI] [PubMed] [Google Scholar]
  26. Salser W. Globin mRNA sequences: analysis of base pairing and evolutionary implications. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 2):985–1002. doi: 10.1101/sqb.1978.042.01.099. [DOI] [PubMed] [Google Scholar]
  27. Scheffler I. E., Elson E. L., Baldwin R. L. Helix formation by d(TA) oligomers. II. Analysis of the helix-coli transitions of linear and circular oligomers. J Mol Biol. 1970 Feb 28;48(1):145–171. doi: 10.1016/0022-2836(70)90225-1. [DOI] [PubMed] [Google Scholar]
  28. Steger G., Hofmann H., Förtsch J., Gross H. J., Randles J. W., Sänger H. L., Riesner D. Conformational transitions in viroids and virusoids: comparison of results from energy minimization algorithm and from experimental data. J Biomol Struct Dyn. 1984 Dec;2(3):543–571. doi: 10.1080/07391102.1984.10507591. [DOI] [PubMed] [Google Scholar]
  29. Sugimoto N., Kierzek R., Freier S. M., Turner D. H. Energetics of internal GU mismatches in ribooligonucleotide helixes. Biochemistry. 1986 Sep 23;25(19):5755–5759. doi: 10.1021/bi00367a061. [DOI] [PubMed] [Google Scholar]
  30. Suurkuusk J., Alvarez J., Freire E., Biltonen R. Calorimetric determination of the heat capacity changes associated with the conformational transitions of polyriboadenylic acid and polyribouridylic acid. Biopolymers. 1977 Dec;16(12):2641–2652. doi: 10.1002/bip.1977.360161206. [DOI] [PubMed] [Google Scholar]
  31. Tinoco I., Jr, Borer P. N., Dengler B., Levin M. D., Uhlenbeck O. C., Crothers D. M., Bralla J. Improved estimation of secondary structure in ribonucleic acids. Nat New Biol. 1973 Nov 14;246(150):40–41. doi: 10.1038/newbio246040a0. [DOI] [PubMed] [Google Scholar]
  32. Tinoco I., Jr, Uhlenbeck O. C., Levine M. D. Estimation of secondary structure in ribonucleic acids. Nature. 1971 Apr 9;230(5293):362–367. doi: 10.1038/230362a0. [DOI] [PubMed] [Google Scholar]
  33. Uhlenbeck O. C., Martin F. H., Doty P. Self-complementary oligoribonucleotides: effects of helix defects and guanylic acid-cytidylic acid base pairs. J Mol Biol. 1971 Apr 28;57(2):217–229. doi: 10.1016/0022-2836(71)90342-1. [DOI] [PubMed] [Google Scholar]
  34. Woese C. R., Gutell R., Gupta R., Noller H. F. Detailed analysis of the higher-order structure of 16S-like ribosomal ribonucleic acids. Microbiol Rev. 1983 Dec;47(4):621–669. doi: 10.1128/mr.47.4.621-669.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yuan R. C., Steitz J. A., Moore P. B., Crothers D. M. The 3' terminus of 16S rRNA: secondary structure and interaction with ribosomal protein S1. Nucleic Acids Res. 1979 Dec 20;7(8):2399–2418. doi: 10.1093/nar/7.8.2399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zuker M., Stiegler P. Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res. 1981 Jan 10;9(1):133–148. doi: 10.1093/nar/9.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]

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