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Predicting RNA Structure with Vfold

Protocol
First Online:
Part of the Methods in Molecular Biology book series (MIMB, volume 1654)

Abstract

In order to carry out biological functions, RNA molecules must fold into specific three-dimensional (3D) structures. Current experimental methods to determine RNA 3D structures are expensive and time consuming. With the recent advances in computational biology, RNA structure prediction is becoming increasingly reliable. This chapter describes a recently developed RNA structure prediction software, Vfold, a virtual bond-based RNA folding model. The main features of Vfold are the physics-based loop free energy calculations for various RNA structure motifs and a template-based assembly method for RNA 3D structure prediction. For illustration, we use the yybP-ykoY Orphan riboswitch as an example to show the implementation of the Vfold model in RNA structure prediction from the sequence.

Key words

RNA folding Vfold model Loop entropy Template assembly 
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Notes

Acknowledgements

This research was supported by NIH grant R01-GM063732.

References

  1. 1.
    Ladd M, Palmer R (1985) Structure determination by X-ray crystallography. Plenum Press, New York, p 71CrossRefGoogle Scholar
  2. 2.
    Furtig B, Richter C, Wohnert J, Schwalbe H (2003) NMR spectroscopy of RNA. Chembiochem 4(10):936–962. doi:10.1002/cbic.200300700CrossRefPubMedGoogle Scholar
  3. 3.
    Bender W, Davidson N (1976) Mapping of poly (A) sequences in the electron microscope reveals unusual structure of type C oncornavirus RNA molecules. Cell 7(4):595–607. doi:10.1016/0092-8674(76)90210-5CrossRefPubMedGoogle Scholar
  4. 4.
    Proudfoot NJ, Brownlee GG (1976) 3′ non-coding region sequences in eukaryotic messenger RNA. Nat Rev Genet 2(12):211–214. doi:10.1038/263211a0Google Scholar
  5. 5.
    Gardner PP, Giegerich R (2004) A comprehensive comparison of comparative RNA structure prediction approaches. BMC Bioinform 5:140. doi:10.1186/1471-2105-5-140CrossRefGoogle Scholar
  6. 6.
    Mathews DH, Moss WN, Turner DH (2010) Folding and finding RNA secondary structure. Cold Spring Harb Perspect Biol 2:a003665. doi:10.1101/cshperspect.a003665CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Washietl S (2010) Sequence and structure analysis of noncoding RNAs. Methods Mol Biol 609:285–306. doi:10.1007/978-1-60327-241-4_17CrossRefPubMedGoogle Scholar
  8. 8.
    Machado-Lima A, del Portillo HA, Durham AM (2008) Computational methods in noncoding RNA research. J Math Biol 56:15–49. doi:10.1007/s00285-007-0122-6CrossRefPubMedGoogle Scholar
  9. 9.
    Mathews DH, Turner DH (2006) Prediction of RNA secondary structure by free energy minimization. Curr Opin Struct Biol 16:270–278. doi:10.1016/j.sbi.2006.05.010CrossRefPubMedGoogle Scholar
  10. 10.
    Sato K, Kato Y, Akutsu T, Asai K, Sakakibara Y (2012) DAFS: simultaneous aligning and folding of RNA sequences via dual decomposition. Bioinformatics 28(24):3218–3224. doi:10.1093/bioinformatics/bts612CrossRefPubMedGoogle Scholar
  11. 11.
    Mathews DH, Turner DH (2002) Dynalign: an algorithm for finding the secondary structure common to two RNA sequences. J Mol Biol 317(2):191–203. doi:10.1006/jmbi.2001.5351CrossRefPubMedGoogle Scholar
  12. 12.
    Tucker BJ, Breaker RR (2005) Riboswitches as versatile gene control elements. Curr Opin Struct Biol 15(3):342–348. doi:10.1016/j.sbi.2005.05.003CrossRefPubMedGoogle Scholar
  13. 13.
    Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31:3406–3415. doi:10.1093/nar/gkg595CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Bellaousov S, Reuter JS, Seetin MG, Methews DH (2013) RNAstructure: web servers for RNA secondary structure prediction and analysis. Nucleic Acids Res 41:W471–W474. doi:10.1093/nar/gkt290CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Hofacker IL (2003) Vienna RNA secondary structure server. Nucleic Acids Res 31(13):3429–3431. doi:10.1093/nar/gkg599CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    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. doi:10.1093/nar/gkp892CrossRefPubMedGoogle Scholar
  17. 17.
    Tan RK, Petrov AS, Harvey SC (2006) YUP: a molecular simulation program for coarse-grained and multi-scaled models. J Chem Theory Comput 2:529–540. doi:10.1021/ct050323rCrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Jonikas MA, Radmer RJ, Laederach A, Das R, Pearlman S, Herschlag D, Altman RB (2009) Coarse-grained modeling of large RNA molecules with knowledge-based potentials and structural filters. RNA 15:189–199. doi:10.1261/rna.1270809CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Sharma S, Ding F, Dokholyan NV (2008) iFoldRNA: three-dimensional RNA structure prediction and folding. Bioinformatics 24:1951–1952. doi:10.1093/bioinformatics/btn328CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Xia Z, Bell DR, Shi Y, Ren P (2013) RNA 3D structure prediction by using a coarse-grained model and experimental data. J Phys Chem B 117:3135–3144. doi:10.1021/jp400751wCrossRefPubMedGoogle Scholar
  21. 21.
    Das R, Karanicolas J, Baker D (2010) Atomic accuracy in predicting and designing noncanonical RNA structure. Nat Methods 7:291–294. doi:10.1038/nmeth.1433CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Parisien M, Major F (2008) The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data. Nature 452:51–55. doi:10.1038/nature06684CrossRefPubMedGoogle Scholar
  23. 23.
    Cao S, Chen S-J (2011) Physics-based de novo prediction of RNA 3D structures. J Phys Chem B 115:4216–4226. doi:10.1021/jp112059yCrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Xu X, Zhao P, Chen S-J (2014) Vfold: a web server for RNA structure and folding thermodynamics prediction. PloS One 9(9):e107504. doi:10.1371/journal.pone.0107504CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Cao S, Chen S-J (2005) Predicting RNA folding thermodynamics with a reduced chain representation model. RNA 11:1884–1897. doi:10.1261/rna.2109105CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Chen S-J (2008) RNA folding: conformational statistics, folding kinetics, and ion electrostatics. Annu Rev Biophys 37:197–214. doi:10.1146/annurev.biophys.37.032807.125957CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Ferro DR, Hermans J (1971) A different best rigid-body molecular fit routine. Acta Crystallogr A 33:345–347. doi:10.1107/S0567739477000862CrossRefGoogle Scholar
  28. 28.
    Arnott S, Hukins DW, Dover SD (1972) Optimised parameters for RNA double-helices. Biochem Biophys Res Commun 48:1392–1399. doi:10.1016/0006-291X(72)90867-4CrossRefPubMedGoogle Scholar
  29. 29.
    Cao S, Chen S-J (2006) Predicting RNA psuedoknot folding thermodynamics. Nucleic Acids Res 34:2634–2652. doi:10.1093/nar/gkl346CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Cao S, Chen S-J (2009) Predicting structures and stabilities for H-type pseudoknots with inter-helix loop. RNA 15:696–706. doi:10.1261/rna.1429009CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Cao S, Chen S-J (2011) Structure and stability of RNA/RNA kissing complex: with application to HIV dimerization initiation signal. RNA 17:2130–2143. doi:10.1261/rna.026658.111CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Cao S, Chen S-J (2012) A domain-based model for predicting large and complex pseudoknotted structures. RNA Biol 9:200–211. doi:10.4161/rna.18488CrossRefPubMedGoogle Scholar
  33. 33.
    Sarver M, Zirbel CL, Stombaugh J, Mokdad A, Leontis NB (2008) FR3D: finding local and composite recurrent structural motifs in RNA 3D structures. J Math Biol 56(1–2):215–252. doi:10.1007/s00285-007-0110-xPubMedGoogle Scholar
  34. 34.
    Bindewald E, Hayes R, Yingling YG, Kasprzak W, Shapiro BA (2008) RNAJunction: a database of RNA junctions and kissing loops for three-dimensional structural analysis and nanodesign. Nucleic Acids Res 36:D392–D397. doi:10.1093/nar/gkm842CrossRefPubMedGoogle Scholar
  35. 35.
    Popenda M, Szachniuk M, Blazewicz M, Wasik S, Burke EK, Blazewicz J, Adamiak RW (2010) RNA FRABASE 2.0: an advanced web-accessible database with the capacity to search the three-dimensional fragments within RNA structures. BMC Bioinformatics 11:231. doi:10.1186/1471-2105-11-231Google Scholar
  36. 36.
    Petrov AI, Zirbel CL, Leontis NB (2013) Automated classification of RNA 3D motifs and the RNA 3D Motif Atlas. RNA 19(10):1327–1340. doi:10.1261/rna.039438.113CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Darty K, Denise A, Ponty Y (2009) VARNA: interactive drawing and editing of the RNA secondary structure. Bioinformatics 25(15):1974–1975. doi:10.1093/bioinformatics/btp250CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Price IR, Gaballa A, Ding F, Helmann JD, Ke A (2015) Mn(2+)-sensing mechanisms of yybP-ykoY orphan riboswitches. Mol Cell 57(6):1110–1123. doi:10.1016/j.molcel.2015.02.016CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Department of Physics, Informatics InstituteUniversity of MissouriColumbiaUSA

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