THE THERMODYNAMICS OF

■ Abstract DNA secondary structure plays an important role in biology, genotyping diagnostics, a variety of molecular biology techniques, in vitro‐selected DNA catalysts, nanotechnology, and DNA-based computing. Accurate prediction of DNA secondary structure and hybridization using dynamic programming algorithms requires a database of thermodynamic parameters for several motifs including Watson-Crick base pairs, internal mismatches, terminal mismatches, terminal dangling ends, hairpins, bulges, internal loops, and multibranched loops. To make the database useful for predictions under a variety of salt conditions, empirical equations for monovalent and magnesium dependence of thermodynamics have been developed. Bimolecular hybridization is often inhibited by competing unimolecular folding of a target or probe DNA. Powerful numerical methods have been developed to solve multistate-coupled equilibria in bimolecular and higher-order complexes. This review presents the current parameter set available for making accurate DNA structure predictions and also points to future directions for improvement.

[1]  E Schütz,et al.  Oligonucleotide melting temperatures under PCR conditions: nearest-neighbor corrections for Mg(2+), deoxynucleotide triphosphate, and dimethyl sulfoxide concentrations with comparison to alternative empirical formulas. , 2001, Clinical chemistry.

[2]  David I. Lewin,et al.  DNA computing , 2002, Comput. Sci. Eng..

[3]  J. SantaLucia,et al.  Nearest neighbor thermodynamic parameters for internal G.A mismatches in DNA. , 1998, Biochemistry.

[4]  R. Breaker.  DNA aptamers and DNA enzymes. , 1997, Current opinion in chemical biology.

[5]  D. Turner,et al.  A periodic table of symmetric tandem mismatches in RNA. , 1995, Biochemistry.

[6]  G. A. van der Marel,et al.  Hairpin formation in synthetic oligonucleotides. , 1985, Biochimie.

[7]  K. Breslauer,et al.  Influence of loop residues on the relative stabilities of DNA hairpin structures. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[8]  M. Oellerich,et al.  DNA base bulge vs unmatched end formation in probe-based diagnostic insertion/deletion genotyping: genotyping the UGT1A1 (TA)(n) polymorphism by real-time fluorescence PCR. , 2000, Clinical chemistry.

[9]  D. Lilley,et al.  Thermodynamics of the ColE1 cruciform. Comparisons between probing and topological experiments using single topoisomers. , 1984, Journal of molecular biology.

[10]  J. McCaskill.  The equilibrium partition function and base pair binding probabilities for RNA secondary structure , 1990, Biopolymers.

[11]  R. Cedergren,et al.  The conformation of single-stranded nucleic acids tDNA versus tRNA. , 1990, European journal of biochemistry.

[12]  H. Blöcker,et al.  Predicting DNA duplex stability from the base sequence. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. Turner,et al.  Measuring the thermodynamics of RNA secondary structure formation. , 1997, Biopolymers.

[14]  Naoki Sugimoto,et al.  Immobilized small deoxyribozyme to distinguish RNA secondary structures. , 2002, Biochemistry.

[15]  H R Garner,et al.  PRIMO: A primer design program that applies base quality statistics for automated large-scale DNA sequencing. , 1997, Genomics.

[16]  J. SantaLucia,et al.  Thermodynamics and NMR of internal G.T mismatches in DNA. , 1997, Biochemistry.

[17]  N C Seeman,et al.  Thermodynamics of DNA branching. , 1992, Journal of Molecular Biology.

[18]  M. Russel.  Mutants at conserved positions in gene IV, a gene required for assembly and secretion of filamentous phages , 1994, Molecular microbiology.

[19]  S. Hecht,et al.  Fe.bleomycin cleaves a transfer RNA precursor and its "transfer DNA" analog at the same major site. , 1993, The Journal of biological chemistry.

[20]  C. W. Hilbers,et al.  Effects of base sequence on the loop folding in DNA hairpins. , 1989, Biochemistry.

[21]  F. Studier,et al.  DNA sequencing by primer walking with strings of contiguous hexamers. , 1992, Science.

[22]  C. E. Longfellow,et al.  Thermodynamic and spectroscopic study of bulge loops in oligoribonucleotides. , 1990, Biochemistry.

[23]  D A LeBlanc,et al.  Thermodynamic characterization of deoxyribooligonucleotide duplexes containing bulges. , 1991, Biochemistry.

[24]  N. Leontis,et al.  Relative stabilities of DNA three-way, four-way and five-way junctions (multi-helix junction loops): unpaired nucleotides can be stabilizing or destabilizing. , 1995, Nucleic acids research.

[25]  D. Turner,et al.  Stability of XGCGCp, GCGCYp, and XGCGCYp helixes: an empirical estimate of the energetics of hydrogen bonds in nucleic acids. , 1986, Biochemistry.

[26]  I. Tinoco,et al.  Thermodynamic parameters for loop formation in RNA and DNA hairpin tetraloops. , 1992, Nucleic acids research.

[27]  I. Tinoco,et al.  How RNA folds. , 1999, Journal of molecular biology.

[28]  Sheldon J. McKay,et al.  AcePrimer: automation of PCR primer design based on gene structure , 2002, Bioinform..

[29]  D. Turner,et al.  Improved free-energy parameters for predictions of RNA duplex stability. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[30]  J. Sabina,et al.  Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. , 1999, Journal of molecular biology.

[31]  A. S. Benight,et al.  Analysis of melting transitions of the DNA hairpins formed from the oligomer sequences d[GGATAC(X)4GTATCC] (X = A, T, G, C) , 1990, Biopolymers.

[32]  David Sankoff,et al.  RNA secondary structures and their prediction , 1984 .

[33]  K. Guckian,et al.  Experimental Measurement of Aromatic Stacking Affinities in the Context of Duplex DNA. , 1996, Journal of the American Chemical Society.

[34]  Roger A. Jones,et al.  Influence of dangling thymidine residues on the stability and structure of two DNA duplexes. , 1988, Biochemistry.

[35]  N. Leontis,et al.  Stability and structure of three-way DNA junctions containing unpaired nucleotides. , 1991, Nucleic acids research.

[36]  L. Makowski,et al.  Construction of a microphage variant of filamentous bacteriophage. , 1992, Journal of molecular biology.

[37]  D. Turner,et al.  Base-stacking and base-pairing contributions to helix stability: thermodynamics of double-helix formation with CCGG, CCGGp, CCGGAp, ACCGGp, CCGGUp, and ACCGGUp. , 1983, Biochemistry.

[38]  F. Kramer,et al.  Thermodynamic basis of the enhanced specificity of structured DNA probes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[39]  A Libchaber,et al.  Sequence dependent rigidity of single stranded DNA. , 2000, Physical review letters.

[40]  K Watanabe,et al.  Extraordinarily stable mini-hairpins: electrophoretical and thermal properties of the various sequence variants of d(GCGAAAGC) and their effect on DNA sequencing. , 1992, Nucleic acids research.

[41]  V. Blinov,et al.  Computer-assisted predictions of the secondary structure in the plant virus single-stranded DNA genome. , 1994, Journal of biomolecular structure & dynamics.

[42]  A. E. Walter,et al.  Nearest-neighbor parameters for G.U mismatches: [formula; see text] is destabilizing in the contexts [formula; see text] and [formula; see text] but stabilizing in [formula; see text]. , 1991, Biochemistry.

[43]  W. Rychlik,et al.  A computer program for choosing optimal oligonucleotides for filter hybridization, sequencing and in vitro amplification of DNA. , 1989, Nucleic acids research.

[44]  F. Frank-Kamenetskii,et al.  Simplification of the empirical relationship between melting temperature of DNA, its GC content and concentration of sodium ions in solution. , 1971, Biopolymers.

[45]  J. DeStefano,et al.  Requirements for the catalysis of strand transfer synthesis by retroviral DNA polymerases. , 1991, The Journal of biological chemistry.

[46]  M Vingron,et al.  Primer design for large scale sequencing. , 1998, Nucleic acids research.

[47]  N. Seeman.  DNA engineering and its application to nanotechnology. , 1999, Trends in biotechnology.

[48]  A. Higashitani,et al.  Nucleotide sequence of the primer RNA for DNA replication of filamentous bacteriophages , 1993, Journal of virology.

[49]  D. Turner,et al.  Predicting oligonucleotide affinity to nucleic acid targets. , 1999, RNA.

[50]  B. Roe,et al.  Aminoacylation of synthetic DNAs corresponding to Escherichia coli phenylalanine and lysine tRNAs. , 1988, Science.

[51]  Douglas H Turner,et al.  RNA pseudoknots , 1992, Current Biology.

[52]  R. Wartell,et al.  Influence of neighboring base pairs on the stability of single base bulges and base pairs in a DNA fragment. , 1995, Biochemistry.

[53]  Chemical probing of tDNAPhe with transition metal complexes: a structural comparison of RNA and DNA. , 1993, Biochemistry.

[54]  D. Turner,et al.  RNA structure prediction. , 1988, Annual review of biophysics and biophysical chemistry.

[55]  Edward C. Holmes,et al.  Primer Master: a new program for the design and analysis of PCR primers , 1996, Comput. Appl. Biosci..

[56]  M. Zuker.  On finding all suboptimal foldings of an RNA molecule. , 1989, Science.

[57]  P. Vallone,et al.  Predicting sequence-dependent melting stability of short duplex DNA oligomers. , 1997, Biopolymers.

[58]  E Schütz,et al.  Spreadsheet software for thermodynamic melting point prediction of oligonucleotide hybridization with and without mismatches. , 1999, BioTechniques.

[59]  P. Bevilacqua,et al.  Selection for thermodynamically stable DNA tetraloops using temperature gradient gel electrophoresis reveals four motifs: d(cGNNAg), d(cGNABg),d(cCNNGg), and d(gCNNGc). , 2002, Biochemistry.

[60]  D. Turner,et al.  Experimentally derived nearest-neighbor parameters for the stability of RNA three- and four-way multibranch loops. , 2002, Biochemistry.

[61]  Leslie A. Taylor,et al.  Predicting antisense oligonucleotide inhibitory efficacy: a computational approach using histograms and thermodynamic indices , 1992, Nucleic Acids Res..

[62]  I. Nazarenko,et al.  Effect of primary and secondary structure of oligodeoxyribonucleotides on the fluorescent properties of conjugated dyes. , 2002, Nucleic acids research.

[63]  A. S. Benight,et al.  The thermodynamic advantage of DNA oligonucleotide 'stacking hybridization' reactions: energetics of a DNA nick. , 1997, Nucleic acids research.

[64]  Jian-Ying Wang,et al.  Modeling hybridization kinetics. , 2003, Mathematical biosciences.

[65]  D. Ward,et al.  Sequence analysis of the termini of virion and replicative forms of minute virus of mice DNA suggests a modified rolling hairpin model for autonomous parvovirus DNA replication , 1985, Journal of virology.

[66]  J. Summers,et al.  Replication of the genome of a hepatitis B-like virus by reverse transcription of an RNA intermediate , 1982, Cell.

[67]  E Schütz,et al.  Application of a thermodynamic nearest-neighbor model to estimate nucleic acid stability and optimize probe design: prediction of melting points of multiple mutations of apolipoprotein B-3500 and factor V with a hybridization probe genotyping assay on the LightCycler. , 1999, Clinical chemistry.

[68]  K. Aldape,et al.  A model of molecular interactions on short oligonucleotide microarrays , 2003, Nature Biotechnology.

[69]  M. A. Cayless.  Statistical Mechanics (2nd edn) , 1977 .

[70]  J. Szostak,et al.  A DNA metalloenzyme with DNA ligase activity , 1995, Nature.

[71]  J. SantaLucia,et al.  A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[72]  D. Draper,et al.  Effects of single-base bulges on intercalator binding to small RNA and DNA hairpins and a ribosomal RNA fragment. , 1989, Biochemistry.

[73]  J. SantaLucia,et al.  Thermodynamics of internal C.T mismatches in DNA. , 1998, Nucleic acids research.

[74]  R R Breaker,et al.  A DNA enzyme that cleaves RNA. , 1994, Chemistry & biology.

[75]  Richard Owczarzy,et al.  Studies of DNA dumbbells VII: Evaluation of the next‐nearest‐neighbor sequence‐dependent interactions in duplex DNA , 1999, Biopolymers.

[76]  N. Leontis,et al.  The thermodynamics of formation of a three-strand, DNA three-way junction complex. , 1994, Biochemistry.

[77]  S. Inouye,et al.  Biosynthesis and structure of stable branched RNA covalently linked to the 5′ end of multicopy single-stranded DNA of Stigmatella aurantiaca , 1987, Cell.

[78]  J. Taylor,et al.  Template switching by reverse transcriptase during DNA synthesis , 1990, Journal of virology.

[79]  G. Grinstein,et al.  Modeling of DNA microarray data by using physical properties of hybridization , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[80]  J. SantaLucia,et al.  Thermodynamic parameters for DNA sequences with dangling ends. , 2000, Nucleic acids research.

[81]  J. SantaLucia,et al.  Nearest-neighbor thermodynamics of internal A.C mismatches in DNA: sequence dependence and pH effects. , 1998, Biochemistry.

[82]  L. Marky,et al.  Differential hydration of dA.dT base pairing and dA and dT bulges in deoxyoligonucleotides. , 1991, Biochemistry.

[83]  G. Varani.  Exceptionally stable nucleic acid hairpins. , 1995, Annual review of biophysics and biomolecular structure.

[84]  R. Murugan.  Revised theory on DNA renaturation kinetics and its experimental verification. , 2002, Biochemical and biophysical research communications.

[85]  Effect of sequence on the structure of three-arm DNA junctions. , 1991, Biochemistry.

[86]  A. Marquis Gacy,et al.  Trinucleotide repeats that expand in human disease form hairpin structures in vitro , 1995, Cell.

[87]  P. Vallone,et al.  Melting studies of short DNA hairpins: influence of loop sequence and adjoining base pair identity on hairpin thermodynamic stability. , 1999, Biopolymers.

[88]  N. Young,et al.  Replication of the B19 parvovirus in human bone marrow cell cultures. , 1986, Science.

[89]  I. Tinoco,et al.  A thermodynamic study of unusually stable RNA and DNA hairpins. , 1991, Nucleic acids research.

[90]  Homer Jacobson,et al.  Intramolecular Reaction in Polycondensations. I. The Theory of Linear Systems , 1950 .

[91]  P. Riccelli,et al.  Hybridization of single-stranded DNA targets to immobilized complementary DNA probes: comparison of hairpin versus linear capture probes. , 2001, Nucleic acids research.

[92]  J. Hearst,et al.  Identification of a structural hairpin in the filamentous chimeric phage M13Gori1. , 1981, Journal of molecular biology.