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VarGibbs Usage in the Optimization of Nearest-Neighbor Parameters and Prediction of Melting Temperature of RNA Duplexes

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RNA Folding

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2726))

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Abstract

The nearest-neighbor (NN) model is a general tool for the evaluation for oligonucleotide thermodynamic stability. It is primarily used for the prediction of melting temperatures but has also found use in RNA secondary structure prediction and theoretical models of hybridization kinetics. One of the key problems is to obtain the NN parameters from melting temperatures, and VarGibbs was designed to obtain those parameters directly from melting temperatures. Here we will describe the basic workflow from RNA melting temperatures to NN parameters with the use of VarGibbs. We start by a brief revision of the basic concepts of RNA hybridization and of the NN model and then show how to prepare the data files, run the parameter optimization, and interpret the results.

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References

  1. Borer PN, Dengler B, Tinoco Jr I, Uhlenbeck OC (1974) Stability of ribonucleic acid double-stranded helices. J Mol Biol 86(4):843–853. https://doi.org/10.1016/0022-2836(74)90357-X

  2. Chamberlin M, Baldwin RL, Berg P (1963) An enzymically synthesized RNA of alternating base sequence: physical and chemical characterization. J Mol Biol 7(4):334–349, 1963. https://doi.org/10.1016/S0022-2836(63)80028-5

  3. Freier SM, Petersheim M, Hickey DR, Turner DH (1984) Thermodynamic studies of RNA stability. J Biomol Struct Dyn 1(5):1229–1242. https://doi.org/10.1080/07391102.1984.10507514

  4. 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 USA 83(24):9373–9377. https://doi.org/10.1073/pnas.83.24.9373

  5. Xia T, SantaLucia Jr J, 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 base pairs. Biochem 37:14719–14735. https://doi.org/10.1021/bi9809425

  6. Ferreira I, Jolley EA, Znosko BM, Weber G (2019) Replacing salt correction factors with optimized RNA nearest-neighbour enthalpy and entropy parameters. Chem Phys 521:69–76. https://doi.org/10.1016/j.chemphys.2019.01.016. https://www.sciencedirect.com/science/article/abs/pii/S0301010418311200

  7. Tinoco I, Uhlenbeck OC, Levine MD (1971) Estimation of secondary structure in ribonucleic acids. Nature 230(5293):362–367

    Google Scholar 

  8. Turner DH, Sugimoto N, Freier SM (1988) RNA structure prediction. Annu Rev Biophys Biophys Chem 17(1):67–192. https://doi.org/10.1146/annurev.bb.17.060188.001123

  9. Mathews DH, Sabina J, Zuker M, Turner DH (1999) Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J Mol Biol 288(5):911–940. https://doi.org/10.1006/jmbi.1999.2700

  10. 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(17):4912–4924. https://doi.org/10.1093/nar/gkl472

  11. Gruber AR, Bernhart SH, Hofacker IL, Washietl S (2008) Strategies for measuring evolutionary conservation of RNA secondary structures. BMC Bioinformat 9(1):1–19. https://doi.org/10.1186/1471-2105-9-122

  12. Spasic A, Berger KD, Chen JL, Seetin MG, Turner DH, Mathews DH (2018) Improving RNA nearest neighbor parameters for helices by going beyond the two-state model. Nucleic Acids Res 46(10):4883–4892. https://doi.org/10.1093/nar/gky270

  13. Costa PR, Acencio ML, Lemke N (2013) Cooperative RNA polymerase molecules behavior on a stochastic sequence-dependent model for transcription elongation. PLoS One 8(2):e57328

    Google Scholar 

  14. Mathews DH, Burkard ME, Freier SM, Wyatt JR, Turner DH (1999) Predicting oligonucleotide affinity to nucleic acid targets. RNA 5(11):1458–1469

    Google Scholar 

  15. Joyeux M, Sahin B (2005) Dynamical model based on finite stacking enthalpies for homogeneous and inhomogeneous DNA thermal denaturation. Phys Rev E 72:051902. https://doi.org/10.1103/PhysRevE.72.051902

  16. Weber G (2011) Finite enthalpy model parameters from DNA melting temperatures. Europhys Lett 96:68001. https://doi.org/10.1209/0295-5075/96/68001. http://iopscience.iop.org/0295-5075/96/6/68001

  17. 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. Biopoly 42(7):783–793. https://doi.org/10.1002/(SICI)1097-0282(199712)42:7%3C783::AID-BIP4%3E3.0.CO;2-P

  18. Gray DM (1997) Derivation of nearest-neighbor properties from data on nucleic acid oligomers. II. thermodynamic parameters of dna· RNA hybrids and dna duplexes. Biopoly 42(7):795–810. https://doi.org/10.1002/(SICI)1097-0282(199712)42:7%3C795::AID-BIP5%3E3.0.CO;2-O

  19. Marky LA, Breslauer KJ (1987) Calculating thermodynamic data for transitions of any molecularity from equilibrium melting curves. Biopoly 26(9):1601–1620. https://doi.org/10.1002/bip.360260911

  20. Breslauer KJ, Frank R, Blocker H, Marky LA (1986) Predicting DNA duplex stability from the base sequence. Proc Natl Acad Sci USA 83(11):3746–3750. https://doi.org/10.1073/pnas.83.11.3746

  21. Weber G (2015) Optimization method for obtaining nearest-neighbour DNA entropies and enthalpies directly from melting temperatures. Bioinformatics 31(6):871–877. https://doi.org/10.1093/bioinformatics/btu751. http://bioinformatics.oxfordjournals.org/content/31/6/871

  22. Chen H, Zhu G (1997) Computer program for calculating the melting temperature of degenerate oligonucleotides used in PCR or hybridization. Biotechniques 22(6):1158–1160. https://doi.org/10.2144/97226bc04

  23. Schütz E, von Ahsen N (1999) Spreadsheet software for thermodynamic melting point prediction of oligonucleotide hybridization with and without mismatches. BioTechniques 27(6):1218–1224. https://doi.org/10.2144/99276bc04

  24. Le Novere N (2001) Melting, computing the melting temperature of nucleic acid duplex. Bioinformatics 17(12):1226–1227

    Google Scholar 

  25. Panjkovich A, Melo F (2005) Comparison of different melting temperature calculation methods for short DNA sequences. Bioinformatics 21(6):711–722. https://doi.org/10.1093/bioinformatics/bti066. http://bioinformatics.oxfordjournals.org/cgi/content/abstract/21/6/711

  26. Licinio P, Guerra JCO (2007) Irreducible representation for nucleotide sequence physical properties and self-consistency of nearest-neighbor dimer sets. Biophys J 92(6):2000–2006. https://doi.org/10.1529/biophysj.106.095059

  27. SantaLucia Jr J, Allawi HT, Seneviratne PA (1996) Improved nearest-neighbour parameters for predicting DNA duplex stability. Biochem 35:3555–3562. https://doi.org/10.1021/bi951907q

  28. Thompson A, Taylor BN (2008) Guide for the Use of the International System of Units (SI). National Institute of Standards and Technology Special Publication 811, Gaithersburg

    Google Scholar 

  29. Schreiber-Gosche S, Edwards S (2009) Thermodynamics of oligonucleotide duplex melting. J Chem Educ 86(5):644. https://doi.org/10.1021/ed086p644

  30. SantaLucia Jr J (1998) A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics. Proc Natl Acad Sci USA 95(4):1460–1465. https://doi.org/10.1073/pnas.95.4.1460. http://www.pnas.org/cgi/content/abstract/95/4/1460

  31. de Oliveira Martins E, Weber G (2017) An asymmetric mesoscopic model for single bulges in RNA. J Chem Phys 147:155102. https://doi.org/10.1063/1.5006948

  32. Miranda P, Oliveira LM, Weber G (2017) Mesoscopic modelling of Cy3 and Cy5 dyes attached to DNA duplexes. Biophys Chem 230C:62–67. ISSN 0301-4622. https://doi.org/10.1016/j.bpc.2017.08.007. http://www.sciencedirect.com/science/article/pii/S0301462217302831

  33. Chen JL, Dishler AL, Kennedy SD, Yildirim I, Liu B, Turner DH, Serra MJ (2012) Testing the nearest neighbor model for canonical RNA base pairs: revision of GU parameters. Biochem 51(16):3508–3522. https://doi.org/10.1021/bi3002709

  34. Nelder JA, Mead R (1965) A simplex method for function minimization. Comput J 7(4):308–313

    Google Scholar 

  35. SLURM Workload Manager. https://slurm.schedmd.com/

  36. Barbosa VB, de Oliveira Martins E, Weber G (2019) Nearest-neighbour parameters optimized for melting temperature prediction of DNA/RNA hybrids at high and low salt concentrations. Biophys Chem 251C:106189. https://doi.org/10.1016/j.bpc.2019.106189

  37. Chen Z, Znosko BM (2013) Effect of sodium ions on RNA duplex stability. Biochem 52(42):7477–7485. https://doi.org/10.1021/bi4008275

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Funding Acknowledgment

This work is supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil).

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Authors and Affiliations

  1. Departamento de Física, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil

    Izabela Ferreira & Gerald Weber

Authors
  1. Izabela Ferreira
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  2. Gerald Weber
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Editors and Affiliations

  1. Institute for Theoretical Chemistry, University of Vienna, Wien, Wien, Austria

    Ronny Lorenz

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Ferreira, I., Weber, G. (2024). VarGibbs Usage in the Optimization of Nearest-Neighbor Parameters and Prediction of Melting Temperature of RNA Duplexes. In: Lorenz, R. (eds) RNA Folding. Methods in Molecular Biology, vol 2726. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3519-3_2

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  • DOI: https://doi.org/10.1007/978-1-0716-3519-3_2

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3518-6

  • Online ISBN: 978-1-0716-3519-3

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