Skip to main content

The Determination of RNA Folding Nearest Neighbor Parameters

  • Protocol
  • First Online:
RNA Sequence, Structure, and Function: Computational and Bioinformatic Methods

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1097))

Abstract

The stability of RNA secondary structure can be predicted using a set of nearest neighbor parameters. These parameters are widely used by algorithms that predict secondary structure. This contribution introduces the UV optical melting experiments that are used to determine the folding stability of short RNA strands. It explains how the nearest neighbor parameters are chosen and how the values are fit to the data. A sample nearest neighbor calculation is provided. The contribution concludes with new methods that use the database of sequences with known structures to determine parameter values.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Zuker M, Stiegler P (1981) Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res 9:133–148

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. McCaskill JS (1990) The equilibrium partition function and base pair probabilities for RNA secondary structure. Biopolymers 29:1105–1119

    Article  CAS  PubMed  Google Scholar 

  3. Ding Y, Lawrence CE (2003) A statistical sampling algorithm for RNA secondary structure prediction. Nucleic Acids Res 31: 7280–7301

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Uhlenbeck OC, Martin FH, Doty P (1971) Self-complementary oligoribonucleotides: effects of helix defects and guanylic acid-cytidylic acid base pairs. J Mol Biol 57:217–229

    Article  CAS  PubMed  Google Scholar 

  5. Martin FH, Uhlenbeck OC, Doty P (1971) Self-complementary oligoribonucleotides: adenylic acid-uridylic acid block copolymers. J Mol Biol 57:201–215

    Article  CAS  PubMed  Google Scholar 

  6. Thach RE (1966) Enzymatic synthesis of oligonucleotide of defined sequence. In: Cantoni GL, Davies DR (eds) Procedures in nucleic acid research. Harper and Row, New York, pp 520–524

    Google Scholar 

  7. Manning GS (1978) The molecular theory of polyelectrolyte solutions with applications to the electrostatic properties of polynucleotides. Q Rev Biophys 11:179–246

    Article  CAS  PubMed  Google Scholar 

  8. Borer PN, Dengler B, Tinoco I Jr, Uhlenbeck OC (1974) Stability of ribonucleic acid double-stranded helices. J Mol Biol 86:843–853

    Article  CAS  PubMed  Google Scholar 

  9. Gray DM (1997) Derivation of nearest-neighbor properties from data on nucleic acid oligomers. II. Thermodynamic parameters of DNA.RNA hybrids and DNA duplexes. Biopolymers 42:795–810

    Article  CAS  PubMed  Google Scholar 

  10. Gray DM (1997) Derivation of nearest-neighbor properties from data on nucleic acid oligomers. I. Simple sets of independent sequences and the influence of absent nearest neighbors. Biopolymers 42:783–793

    Article  CAS  PubMed  Google Scholar 

  11. Gralla J, Crothers DM (1973) Free energy of imperfect nucleic acid helices. 3. Small internal loops resulting from mismatches. J Mol Biol 78:301–319

    Article  CAS  PubMed  Google Scholar 

  12. Gralla J, Crothers DM (1973) Free energy of imperfect nucleic acid helices. II. Small hairpin loops. J Mol Biol 73:497–511

    Article  CAS  PubMed  Google Scholar 

  13. Uhlenbeck OC, Cameron V (1977) Equimolar addition of oligoribonucleotides with T4 RNA ligase. Nucleic Acids Res 4:85–98

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. England TE, Neilson T (1977) Duplex formation of complementary oligoribonucleotides corresponding to the dihydrouridine loop neck region of several transfer ribonucleic acids. Can J Biochem 55:365–368

    Article  CAS  PubMed  Google Scholar 

  15. Kierzek R, Caruthers MH, Longfellow CE, Swinton D, Turner DH, Freier SM (1986) Polymer-supported synthesis and its application to test the nearest-neighbor model for duplex stability. Biochemistry 25: 7840–7846

    Article  CAS  PubMed  Google Scholar 

  16. Freier SM, Kierzek R, Jaeger JA, Sugimoto N, Caruthers MH, Neilson T, Turner DH (1986) Improved free-energy parameters for predictions of RNA duplex stability. Proc Natl Acad Sci U S A 83:9373–9377

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Usman N, Ogilvie KK, Jiang MY, Cedergren RJ (1987) The automated chemical synthesis of long oligoribonucleotides using 2'-O-silylated ribonucleoside 3'-O-phosphoramidites on a controlled-pore glass support: synthesis of a 43-nucleotide sequence similar to the 3'-half molecule of an Escherichia coli formylmethionine tRNA. J Am Chem Soc 109:7485–7854

    Article  Google Scholar 

  18. Wincott F, DiRenzo A, Shaffer C, Grimm S, Tracz D, Workman C, Sweedler D, Gonzalez C, Scaringe S, Usman N (1995) Synthesis, deprotection, analysis and purification of RNA and ribozymes. Nucleic Acids Res 23:2677–2684

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Turner DH (2000) Conformational changes. In: Bloomfield V, Crothers D, Tinoco I (eds) Nucleic acids. University Science Books, Sausalito, CA, pp 259–334

    Google Scholar 

  20. Xia T, SantaLucia J Jr, Burkard ME, Kierzek R, Schroeder SJ, Jiao X, Cox C, Turner DH (1998) Thermodynamic parameters for an expanded nearest-neighbor model for formation of RNA duplexes with Watson-Crick pairs. Biochemistry 37:14719–14735

    Article  CAS  PubMed  Google Scholar 

  21. McDowell JA, Turner DH (1996) Investigation of the structural basis for thermodynamic stabilities of tandem GU mismatches: solution structure of (rGAGGUCUC)2 by two-dimensional NMR and simulated annealing. Biochemistry 35:14077–14089

    Article  CAS  PubMed  Google Scholar 

  22. Petersheim M, Turner DH (1983) Base-stacking and base-pairing contributions to helix stability: thermodynamics of double-helix formation with CCGG, CCGGp, CCGGAp, ACCGGp, CCGGUp, and ACCGGUp. Biochemistry 22:256–263

    Article  CAS  PubMed  Google Scholar 

  23. Albergo DD, Marky LA, Breslauer KJ, Turner DH (1981) Thermodynamics of (dG–dC)3 double-helix formation in water and deuterium oxide. Biochemistry 20:1409–1413

    Article  CAS  PubMed  Google Scholar 

  24. Hartsel SA, Kitchen DE, Scaringe SA, Marshall WS (2005) RNA oligonucleotide synthesis via 5'-silyl-2'-orthoester chemistry. Methods Mol Biol 288:33–50

    CAS  PubMed  Google Scholar 

  25. Scaringe SA, Wincott FE, Caruthers MH (1998) Novel RNA synthesis method using 5'-O-silyl-2'-O-orthoester protecting groups. J Am Chem Soc 120:11820–11821

    Article  CAS  Google Scholar 

  26. Siegfried NA, Bevilacqua PC (2009) Thinking inside the box: designing, implementing, and interpreting thermodynamic cycles to dissect cooperativity in RNA and DNA folding. Methods Enzymol 455:365–393

    Article  CAS  PubMed  Google Scholar 

  27. Schroeder SJ, Turner DH (2009) Optical melting measurements of nucleic acid thermodynamics. Methods Enzymol 468:371–387

    Article  CAS  PubMed  Google Scholar 

  28. Cantor CR, Schimmel PR (1980) Biophysical chemistry. W. H. Freeman and Company, New York

    Google Scholar 

  29. Mikulecky PJ, Feig AL (2006) Heat capacity changes associated with nucleic acid folding. Biopolymers 82:38–58

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Chaires JB (1997) Possible origin of differences between van’t Hoff and calorimetric enthalpy estimates. Biophys Chem 64: 15–23

    Article  CAS  PubMed  Google Scholar 

  31. Lu ZJ, Turner DH, Mathews DH (2006) A set of nearest neighbor parameters for predicting the enthalpy change of RNA secondary structure formation. Nucleic Acids Res 34:4912–4924

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Breslauer KJ, Frank R, Blocker H, Marky LA (1986) Predicting DNA duplex stability from the base sequence. Proc Natl Acad Sci U S A 83:3746–3750

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. SantaLucia J Jr, Allawi HT, Seneviratne PA (1996) Improved nearest-neighbor parameters for predicting DNA duplex stability. Biochemistry 35:3555–3562

    Article  CAS  PubMed  Google Scholar 

  34. Sugimoto N, Nakano S, Yoneyama M, Honda K (1996) Improved thermodynamic parameters and helix initiation factor to predict stability of DNA duplexes. Nucleic Acids Res 24:4501–4505

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Ma H, Proctor DJ, Kierzek E, Kierzek R, Bevilacqua PC, Gruebele M (2006) Exploring the energy landscape of a small RNA hairpin. J Am Chem Soc 128:1523–1530

    Article  CAS  PubMed  Google Scholar 

  36. Proctor DJ, Ma H, Kierzek E, Kierzek R, Gruebele M, Bevilacqua PC (2004) Folding thermodynamics and kinetics of YNMG RNA hairpins: specific incorporation of 8-bromoguanosine leads to stabilization by enhancement of the folding rate. Biochemistry 43:14004–14014

    Article  CAS  PubMed  Google Scholar 

  37. Feig AL (2009) Studying RNA–RNA and RNA–protein interactions by isothermal titration calorimetry. Methods Enzymol 468:409–422

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Breslauer KJ, Freire E, Straume M (1992) Calorimetry: a tool for DNA and ligand-DNA studies. Methods Enzymol 211:533–567

    Article  CAS  PubMed  Google Scholar 

  39. Mathews DH, Sabina J, Zuker M, Turner DH (1999) Expanded sequence dependence of thermodynamic parameters provides improved prediction of RNA secondary structure. J Mol Biol 288:911–940

    Article  CAS  PubMed  Google Scholar 

  40. Wu M, McDowell JA, Turner DH (1995) A periodic table of symmetric tandem mismatches in RNA. Biochemistry 34:3204–3211

    Article  CAS  PubMed  Google Scholar 

  41. Hickey DR, Turner DH (1985) Solvent effects on the stability of A7U7p. Biochemistry 24:2086–2094

    Article  CAS  PubMed  Google Scholar 

  42. Freier SM, Kierzek R, Caruthers MH, Neilson T, Turner DH (1986) Free energy contributions of G.U and other terminal mismatches to helix stability. Biochemistry 25:3209–3223

    Article  CAS  PubMed  Google Scholar 

  43. Freier SM, Sugimoto N, Sinclair A, Alkema D, Neilson T, Kierzek R, Caruthers MH, Turner DH (1986) Stability of XGCGCp, GCGCYp, and XGCGCYp helixes: an empirical estimate of the energetics of hydrogen bonds in nucleic acids. Biochemistry 25:3214–3219

    Article  CAS  PubMed  Google Scholar 

  44. Sugimoto N, Kierzek R, Turner DH (1987) Sequence dependence for the energetics of dangling ends and terminal base pairs in ribonucleic acid. Biochemistry 26:4554–4558

    Article  CAS  PubMed  Google Scholar 

  45. Serra MJ, Axenson TJ, Turner DH (1994) A model for the stabilities of RNA hairpins based on a study of the sequence dependence of stability for hairpins of six nucleotides. Biochemistry 33:14289–14296

    Article  CAS  PubMed  Google Scholar 

  46. Dale T, Smith R, Serra M (2000) A test of the model to predict unusually stable RNA hairpin loop stability. RNA 6:608–615

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Mathews DH, Disney MD, Childs JL, Schroeder SJ, Zuker M, Turner DH (2004) Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. Proc Natl Acad Sci U S A 101:7287–7292

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Hofacker IL, Fekete M, Stadler PF (2002) Secondary structure prediction for aligned RNA sequences. J Mol Biol 319:1059–1066

    Article  CAS  PubMed  Google Scholar 

  49. Mathews DH, Turner DH (2002) Dynalign: an algorithm for finding the secondary structure common to two RNA sequences. J Mol Biol 317:191–203

    Article  CAS  PubMed  Google Scholar 

  50. Mathews DH, Turner DH (2002) Experimentally derived nearest neighbor parameters for the stability of RNA three- and four-way multibranch loops. Biochemistry 41:869–880

    Article  CAS  PubMed  Google Scholar 

  51. Liu B, Diamond JM, Mathews DH, Turner DH (2011) Fluorescence competition and optical melting measurements of RNA three-way multibranch loops provide a revised model for thermodynamic parameters. Biochemistry 50:640–653

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Mathews DH (2004) Using an RNA secondary structure partition function to determine confidence in base pairs predicted by free energy minimization. RNA 10:1178–1190

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Mathews DH (2005) Predicting a set of minimal free energy RNA secondary structures common to two sequences. Bioinformatics 21:2246–2253

    Article  CAS  PubMed  Google Scholar 

  54. Freier SM, Burger BJ, Alkema D, Neilson T, Turner DH (1983) Effects of 3' dangling end stacking on the stability of GGCC and CCGG double helices. Biochemistry 22:6198–6206

    Article  CAS  Google Scholar 

  55. Freier SM, Alkema D, Sinclair A, Neilson T, Turner DH (1985) Contributions of dangling end stacking and terminal base-pair formation to the stabilities of XGGCCp, XCCGGp, XGGCCYp, and XCCGGYp helixes. Biochemistry 24:4533–4539

    Article  CAS  PubMed  Google Scholar 

  56. Turner DH, Sugimoto N, Freier SM (1988) RNA structure prediction. Ann Rev Biophys Biophys Chem 17:167–192

    Article  CAS  Google Scholar 

  57. Longfellow CE, Kierzek R, Turner DH (1990) Thermodynamic and spectroscopic study of bulge loops in oligoribonucleotides. Biochemistry 29:278–285

    Article  CAS  PubMed  Google Scholar 

  58. Schroeder SJ, Burkard ME, Turner DH (1999) The energetics of small internal loops in RNA. Biopolymers 52:157–167

    Article  CAS  PubMed  Google Scholar 

  59. Kierzek R, Burkard ME, Turner DH (1999) Thermodynamics of single mismatches in RNA duplexes. Biochemistry 38:14214–14223

    Article  CAS  PubMed  Google Scholar 

  60. Davis AR, Znosko BM (2008) Thermodynamic characterization of naturally occurring RNA single mismatches with G-U nearest neighbors. Biochemistry 47:10178–10187

    Article  CAS  PubMed  Google Scholar 

  61. Davis AR, Znosko BM (2007) Thermodynamic characterization of single mismatches found in naturally occurring RNA. Biochemistry 46:13425–13436

    Article  CAS  PubMed  Google Scholar 

  62. Miller S, Jones LE, Giovannitti K, Piper D, Serra MJ (2008) Thermodynamic analysis of 5' and 3' single- and 3' double-nucleotide overhangs neighboring wobble terminal base pairs. Nucleic Acids Res 36:5652–5659

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Clanton-Arrowood K, McGurk J, Schroeder SJ (2008) 3' terminal nucleotides determine thermodynamic stabilities of mismatches at the ends of RNA helices. Biochemistry 47:13418–13427

    Article  CAS  PubMed  Google Scholar 

  64. Badhwar J, Karri S, Cass CK, Wunderlich EL, Znosko BM (2007) Thermodynamic characterization of RNA duplexes containing naturally occurring 1 × 2 nucleotide internal loops. Biochemistry 46:14715– 14724

    Article  CAS  PubMed  Google Scholar 

  65. Blose JM, Manni ML, Klapec KA, Stranger-Jones Y, Zyra AC, Sim V, Griffith CA, Long JD, Serra MJ (2007) Non-nearest-neighbor dependence of the stability for RNA bulge loops based on the complete set of group I single-nucleotide bulge loops. Biochemistry 46:15123–15135

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. O’Toole AS, Miller S, Serra MJ (2005) Stability of 3' double nucleotide overhangs that model the 3' ends of siRNA. RNA 11:512–516

    Article  PubMed Central  PubMed  Google Scholar 

  67. Vecenie CJ, Morrow CV, Zyra A, Serra MJ (2006) Sequence dependence of the stability of RNA hairpin molecules with six nucleotide loops. Biochemistry 45:1400–1407

    Article  CAS  PubMed  Google Scholar 

  68. Do CB, Woods DA, Batzoglou S (2006) CONTRAfold: RNA secondary structure prediction without physics-based models. Bioinformatics 22:e90–e98

    Article  CAS  PubMed  Google Scholar 

  69. Andronescu M, Condon A, Hoos HH, Mathews DH, Murphy KP (2007) Efficient parameter estimation for RNA secondary structure prediction. Bioinformatics 23:i19–i28

    Article  CAS  PubMed  Google Scholar 

  70. Andronescu M, Condon A, Hoos HH, Mathews DH, Murphy KP (2010) Computational approaches for RNA energy parameter estimation. RNA 16:2304–2318

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Zakov S, Goldberg Y, Elhadad M, Ziv-Ukelson M (2011) Rich parameterization improves RNA structure prediction. In: Bafna V, Sahinalp, SC (eds) Proceedings of 15th annual international conference on research in computational molecular biology. Springer-Verlag, Berlin, Germany, pp 546–562

    Google Scholar 

  72. Do CB, Foo CS, Batzoglou S (2008) A max-margin model for efficient simultaneous alignment and folding of RNA sequences. Bioinformatics 24:i68–i76

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Andronescu MS, Pop C, Condon AE (2010) Improved free energy parameters for RNA pseudoknotted secondary structure prediction. RNA 16:26–42

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Andronescu M, Bereg V, Hoos HH, Condon A (2008) RNA STRAND: the RNA secondary structure and statistical analysis database. BMC Bioinformatics 9:340

    Article  PubMed Central  PubMed  Google Scholar 

  75. Sprinzl M, Vassilenko KS (2005) Compilation of tRNA sequences and sequences of tRNA genes. Nucleic Acids Res 33:D139–D140

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Cannone JJ, Subramanian S, Schnare MN, Collett JR, D’Souza LM, Du Y, Feng B, Lin N, Madabusi LV, Muller KM et al (2002) The comparative RNA web (CRW) site: an online database of comparative sequence and structure information for ribosomal, intron, and other RNAs. BMC Bioinformatics 3:2

    Article  PubMed Central  PubMed  Google Scholar 

  77. Andersen ES, Rosenblad MA, Larsen N, Westergaard JC, Burks J, Wower IK, Wower J, Gorodkin J, Samuelsson T, Zwieb C (2006) The tmRDB and SRPDB resources. Nucleic Acids Res 34:D163–D168

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Brown JW (1999) The ribonuclease P database. Nucleic Acids Res 27:314

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  79. Walter AE, Turner DH, Kim J, Lyttle MH, Müller P, Mathews DH, Zuker M (1994) Coaxial stacking of helixes enhances binding of oligoribonucleotides and improves predictions of RNA folding. Proc Natl Acad Sci U S A 91:9218–9222

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Kim J, Walter AE, Turner DH (1996) Thermodynamics of coaxially stacked helices with GA and CC mismatches. Biochemistry 35:13753–13761

    Article  CAS  PubMed  Google Scholar 

  81. Meyer IM, Miklos I (2004) Co-transcriptional folding is encoded within RNA genes. BMC Mol Biol 5:10

    Article  PubMed Central  PubMed  Google Scholar 

  82. Mathews DH, Turner DH (2006) Prediction of RNA secondary structure by free energy minimization. Curr Opin Struct Biol 16:270–278

    Article  CAS  PubMed  Google Scholar 

  83. Turner DH, Mathews DH (2010) NNDB: the nearest neighbor parameter database for predicting stability of nucleic acid secondary structure. Nucleic Acids Res 38:D280–D282

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Andronescu M, Zhang ZC, Condon A (2005) Secondary structure prediction of interacting RNA molecules. J Mol Biol 345:987–1001

    Article  CAS  PubMed  Google Scholar 

  85. Hofacker IL, Fontana W, Stadler PF, Bonhoeffer LS, Tacker M, Schuster P (1994) Fast folding and comparison of RNA secondary structures. Monatsh Chem 125: 167–168

    Article  CAS  Google Scholar 

  86. Zuker M, Mathews DH, Turner DH (1999) Algorithms and thermodynamics for RNA secondary structure prediction: a practical guide. In: Barciszewski J, Clark BFC (eds) RNA biochemistry and biotechnology. Kluwer Academic Publishers, Boston, pp 11–43

    Chapter  Google Scholar 

  87. Markham NR, Zuker M (2008) UNAFold: software for nucleic acid folding and hybridization. Methods Mol Biol 453:3–31

    Article  CAS  PubMed  Google Scholar 

  88. Theimer CA, Blois CA, Feigon J (2005) Structure of the human telomerase RNA pseudoknot reveals conserved tertiary interactions essential for function. Mol Cell 17:671–682

    Article  CAS  PubMed  Google Scholar 

  89. Nixon PL, Giedroc DP (2000) Energetics of a strongly pH dependent RNA tertiary structure in a frameshifting pseudoknot. J Mol Biol 296:659–671

    Article  CAS  PubMed  Google Scholar 

  90. Theimer CA, Finger LD, Trantirek L, Feigon J (2003) Mutations linked to dyskeratosis congenita cause changes in the structural equilibrium in telomerase RNA. Proc Natl Acad Sci U S A 100:449–454

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  91. Soto AM, Misra V, Draper DE (2007) Tertiary structure of an RNA pseudoknot is stabilized by “diffuse” Mg2+ ions. Biochemistry 46:2973–2983

    Article  CAS  PubMed  Google Scholar 

  92. Liu B, Shankar N, Turner DH (2010) Fluorescence competition assay measurements of free energy changes for RNA pseudoknots. Biochemistry 49:623–634

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Wyatt JR, Puglisi JD, Tinoco I Jr (1990) RNA pseudoknots, stability and loop size requirements. J Mol Biol 214:455–470

    Article  CAS  PubMed  Google Scholar 

  94. Aalberts DP, Hodas NO (2005) Asymmetry in RNA pseudoknots: observation and theory. Nucleic Acids Res 33:2210–2214

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  95. Gultyaev AP, van Batenburg FHD, Pleij CWA (1999) An approximation of loop free energy values of RNA H-pseudoknots. RNA 5:609–617

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  96. Xayaphoummine A, Bucher T, Thalmann F, Isambert H (2003) Prediction and statistics of pseudoknots in RNA structures using exactly clustered stochastic simulations. Proc Natl Acad Sci U S A 100:15310–15315

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  97. Cao S, Chen SJ (2006) Predicting RNA pseudoknot folding thermodynamics. Nucleic Acids Res 34:2634–2652

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. Cao S, Chen SJ (2009) Predicting structures and stabilities for H-type pseudoknots with interhelix loops. RNA 15:696–706

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Rivas E, Eddy SR (1999) A dynamic programming algorithm for RNA structure prediction including pseudoknots. J Mol Biol 285:2053–2068

    Article  CAS  PubMed  Google Scholar 

  100. Dirks RM, Pierce NA (2003) A partition function algorithm for nucleic acid secondary structure including pseudoknots. J Comput Chem 24:1664–1677

    Article  CAS  PubMed  Google Scholar 

  101. Ren J, Rastegari B, Condon A, Hoos HH (2005) HotKnots: heuristic prediction of RNA secondary structures including pseudoknots. RNA 11:1494–1504

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  102. SantaLucia J, Hicks D (2004) The thermodynamics of DNA structural motifs. Annu Rev Biophys Biomol Struct 33: 415–440

    Article  CAS  PubMed  Google Scholar 

  103. Reuter JS, Mathews DH (2010) RNAstructure: software for RNA secondary structure prediction and analysis. BMC Bioinformatics 11:129

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Jonathan Chen for preparing Figs. 3.1 and 3.2 and Matthew Seetin for helpful comments. The chapter was supported by National Institutes of Health grants R01GM22939 to D.H.T., R01GM076485 to D.H.M., and a grant from the Natural Sciences and Engineering Research Council of Canada to A.C.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David H. Mathews .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Andronescu, M., Condon, A., Turner, D.H., Mathews, D.H. (2014). The Determination of RNA Folding Nearest Neighbor Parameters. In: Gorodkin, J., Ruzzo, W. (eds) RNA Sequence, Structure, and Function: Computational and Bioinformatic Methods. Methods in Molecular Biology, vol 1097. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-709-9_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-709-9_3

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-708-2

  • Online ISBN: 978-1-62703-709-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics