Abstract
RNA 3D structure prediction is analogous to the protein folding problem, particularly the astronomical size of the conformational search space and the challenge of appropriately scoring native versus decoy alternatives. However, RNA presents important differences compared to proteins, notably the existence of a low-energy secondary structure intermediate on the pathway to tertiary folding. The availability of a secondary structure facilitates de novo prediction using assembly of fragments. RNA mutants and close homologs are readily predicted with high accuracy using homology modeling. Evolutionarily distant RNAs often require a combination of homology and de novo modeling approaches. The greatest challenges to RNA structure prediction are posed by multihelix loops, certain types of pseudoknots, and multidomain packing. There are also a variety of partial folding problems for RNA and opportunities for whole database structure prediction. Herein we describe a unified suite of programs called “RNA123” for the analysis and prediction of RNA structure.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Aduri R, Psciuk BT, Saro P, Taniga H, Schlegel HB, SantaLucia J Jr (2007) AMBER force field parameters for the naturally occurring modified nucleosides in RNA. J Chem Theor Comput 3:1464–1475
Alm E, Morozov AV, Kortemme T, Baker D (2002) Simple physical models connect theory and experiment in protein folding kinetics. J Mol Biol 322:463–476
Ben-David M, Noivirt-Brik O, Paz A, Prilusky J, Sussman JL, Levy Y (2009) Assessment of CASP8 structure predictions for template free targets. Proteins 77(Suppl 9):50–65
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:D392–397
Bloomfield VA, Crothers DM, Tinoco IJ (2000) Nucleic acids: structures, properties and functions. University Science, Sausalito, CA
Blum B, Jordan MI, Baker D (2010) Feature space resampling for protein conformational search. Proteins 78:1583–1593
Cate JH, Gooding AR, Podell E, Zhou K, Golden BL, Kundrot CE, Cech TR, Doudna JA (1996) Crystal structure of a group I ribozyme domain: principles of RNA packing. Science 273:1678
Chen Y, Kortemme T, Robertson T, Baker D, Varani G (2004) A new hydrogen-bonding potential for the design of protein-RNA interactions predicts specific contacts and discriminates decoys. Nucleic Acids Res 32:5147–5162
Correll CC, Beneken J, Plantinga MJ, Lubbers M, Chan YL (2003) The common and the distinctive features of the bulged-G motif based on a 1.04 A resolution RNA structure. Nucleic Acids Res 31:6806–6818
Dahiyat BI, Mayo SL (1997) De novo protein design: fully automated sequence selection. Science 278:82–87
Das R, Baker D (2007) Automated de novo prediction of native-like RNA tertiary structures. Proc Natl Acad Sci U S A 104:14664–14669
Das R, Baker D (2008) Macromolecular modeling with rosetta. Annu Rev Biochem 77:363–382
Davis IW, Murray LW, Richardson JS, Richardson DC (2004) MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes. Nucleic Acids Res 32:W615–619
Deigan KE, Li TW, Mathews DH, Weeks KM (2009) Accurate SHAPE-directed RNA structure determination. Proc Natl Acad Sci U S A 106:97–102
Ding F, Sharma S, Chalasani P, Demidov VV, Broude NE, Dokholyan NV (2008) Ab initio RNA folding by discrete molecular dynamics: from structure prediction to folding mechanisms. RNA 14:1164–1173
Draper DE (2008) RNA folding: thermodynamic and molecular descriptions of the roles of ions. Biophys J 95:5489–5495
Duan Y, Kollman PA (1998) Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution. Science 282:740–744
Forster F, Webb B, Krukenberg KA, Tsuruta H, Agard DA, Sali A (2008) Integration of small-angle X-ray scattering data into structural modeling of proteins and their assemblies. J Mol Biol 382:1089–1106
Gardner PP, Daub J, Tate JG, Nawrocki EP, Kolbe DL, Lindgreen S, Wilkinson AC, Finn RD, Griffiths-Jones S, Eddy SR et al (2009) Rfam: updates to the RNA families database. Nucleic Acids Res 37:D136–D140
Gautheret D, Major F, Cedergren R (1993) Modeling the three-dimensional structure of RNA using discrete nucleotide conformational sets. J Mol Biol 229:1049–1064
Godzik A, Kolinski A, Skolnick J (1993) De novo and inverse folding predictions of protein structure and dynamics. J Comput Aided Mol Des 7:397–438
Gorenstein DG (1984) Phosphorus-31 NMR: principles and applications. Academic, Orlando
Gutell RR, Lee JC, Cannone JJ (2002) The accuracy of ribosomal RNA comparative structure models. Curr Opin Struct Biol 12:301–310
Hellinga HW (1997) Rational protein design: combining theory and experiment. Proc Natl Acad Sci U S A 94:10015–10017
Herschlag D (2009) Biophysical, chemical, and functional probes of RNA structure, interactions and folding: Part A. Preface. Methods Enzymol 468:xv
Jaeger JA, Zuker M, Turner DH (1990) Melting and chemical modification of a cyclized self-splicing group I intron: similarity of structures in 1M Na+, in 10 mM Mg2+, and in the presence of substrate. Biochemistry 29:10147–10158
Jaeger JA, SantaLucia J Jr, Tinoco I Jr (1993) Determination of RNA structure and thermodynamics. Annu Rev Biochem 62:255–287
Jagielska A, Wroblewska L, Skolnick J (2008) Protein model refinement using an optimized physics-based all-atom force field. Proc Natl Acad Sci U S A 105:8268–8273
Jones DT (1999) Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol 292:195–202
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
Jossinet F, Ludwig TE, Westhof E (2010) Assemble: an interactive graphical tool to analyze and build RNA architectures at the 2D and 3D levels. Bioinformatics 26:2057–2059
Karanicolas J, Brooks CL (2003) Improved Go-like models demonstrate the robustness of protein folding mechanisms toward non-native interactions. J Mol Biol 334:309–325
Kaufmann KW, Lemmon GH, Deluca SL, Sheehan JH, Meiler J (2010) Practically useful: what the Rosetta protein modeling suite can do for you. Biochemistry 49:2987–2998
Kierzek E, Kierzek R, Turner DH, Catrina IE (2006) Facilitating RNA structure prediction with microarrays. Biochemistry 45:581–593
Koculi E, Thirumalai D, Woodson SA (2006) Counterion charge density determines the position and plasticity of RNA folding transition states. J Mol Biol 359:446–454
Krivov SV, Karplus M (2004) Hidden complexity of free energy surfaces for peptide (protein) folding. Proc Natl Acad Sci U S A 101:14766–14770
Kuhlman B, Dantas G, Ireton GC, Varani G, Stoddard BL, Baker D (2003) Design of a novel globular protein fold with atomic-level accuracy. Science 302:1364–1368
Lamb J, Kwok L, Qiu X, Andresen K, Park HY, Pollack L (2008) Reconstructing three-dimensional shape envelopes from time-resolved small-angle X-ray scattering data. J Appl Crystallogr 41:1046–1052
Lankhorst PP, Haasnoot CA, Erkelens C, Altona C (1984) Carbon-13 NMR in conformational analysis of nucleic acid fragments. 3. The magnitude of torsional angle epsilon in d(TpA) from CCOP and HCOP NMR coupling constants. Nucleic Acids Res 12:5419–5428
Lasker K, Topf M, Sali A, Wolfson HJ (2009) Inferential optimization for simultaneous fitting of multiple components into a CryoEM map of their assembly. J Mol Biol 388:180–194
Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr 26:283–291
Leontis NB, Westhof E (2001) Geometric nomenclature and classification of RNA base pairs. RNA 7:499–512
Leontis NB, Stombaugh J, Westhof E (2002) The non-Watson-Crick base pairs and their associated isostericity matrices. Nucleic Acids Res 30:3497–3531
Looger LL, Dwyer MA, Smith JJ, Hellinga HW (2003) Computational design of receptor and sensor proteins with novel functions. Nature 423:185–190
Lu X-J, Olson KW (2003) 3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures. Nucleic Acids Res 31:5108–5121
Macke TJ, Case DA (1998) Modeling unusual nucleic acid structures. ACS Symp Ser 682:379–393
Maier A, Sklenar H, Kratky HF, Renner A, Schuster P (1999) Force field based conformational analysis of RNA structural motifs: GNRA tetraloops and their pyrimidine relatives. Eur Biophys J Biophys Lett 28:564–573
Major F, Turcotte M, Gautheret D, Lapalme G, Fillion E, Cedergren R (1991) The combination of symbolic and numerical computation for three-dimensional modeling of RNA. Science 253:1255–1260
Massire C, Westhof E (1999) MANIP: An interactive tool for modeling RNA. J Mol Graphics Modeling 16:197–205
Massire C, Jaeger L, Westhof E (1998) Derivation of the three-dimensional architecture of bacterial ribonuclease P RNAs from comparative sequence analysis. J Mol Biol 279:773–793
Mathews DH, Turner DH (2006) Prediction of RNA secondary structure by free energy minimization. Curr Opin Struct Biol 16:270–278
Mathews DH, Sabina J, Zuker M, Turner DH (1999) Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J Mol Biol 288:911–940
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
Merino EJ, Wilkinson KA, Coughlan JL, Weeks KM (2005) RNA structure analysis at single nucleotide resolution by selective 2'-hydroxyl acylation and primer extension (SHAPE). J Am Chem Soc 127:4223–4231
Michel F, Westhof E (1990) Modelling of the three-dimensional architecture of group I catalytic introns based on comparative sequence analysis. J Mol Biol 216:585–610
Misra VK, Shiman R, Draper DE (2003) A thermodynamic framework for the magnesium-dependent folding of RNA. Biopolymers 69:118–136
Mituyama T, Yamada K, Hattori E, Okida H, Ono Y, Terai G, Yoshizawa A, Komori T, Asai K (2009) The functional RNA Database 3.0: databases to support mining and annotation of functional RNAs. Nucleic Acids Res 37:D89–92
Mueller F, Brimacombe R (1997) A new model for the three-dimensional folding of Escherichia coli 16 S ribosomal RNA. I. Fitting the RNA to a 3D electron microscopic map at 20 A. J Mol Biol 271:524–544
Mueller F, Sommer I, Baranov P, Matadeen R, Stoldt M, Wohnert J, Gorlach M, van Heel M, Brimacombe R (2000) The 3D arrangement of the 23 S and 5 S rRNA in the Escherichia coli 50 S ribosomal subunit based on a cryo-electron microscopic reconstruction at 7.5 A resolution. J Mol Biol 298:35–59
Murphy FL, Cech TR (1993) An independently folding domain of RNA tertiary structure within the Tetrahymena ribozyme. Biochemistry 32:5291–5300
Murray LJ, Richardson JS, Arendall WB, Richardson DC (2005) RNA backbone rotamers–finding your way in seven dimensions. Biochem Soc Trans 33:485–487
Nasalean L, Baudrey S, Leontis NB, Jaeger L (2006) Controlling RNA self-assembly to form filaments. Nucleic Acids Res 34:1381–1392
Needleman SB, Wunsch CD (1970) A general method applicable to the search for similarities in amino acid sequence of two proteins. J Mol Biol 48:443–453
Pandit SB, Brylinski M, Zhou H, Gao M, Arakaki AK, Skolnick J (2010) PSiFR: an integrated resource for prediction of protein structure and function. Bioinformatics 26:687–688
Parisien M, Major F (2008) The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data. Nature 452:51–55
Perez A, Marchan I, Svozil D, Sponer J, Cheatham TE 3rd, Laughton CA, Orozco M (2007) Refinement of the AMBER force field for nucleic acids: improving the description of alpha/gamma conformers. Biophys J 92:3817–3829
Raman S, Vernon R, Thompson J, Tyka M, Sadreyev R, Pei J, Kim D, Kellogg E, DiMaio F, Lange O et al (2010) Structure prediction for CASP8 with all-atom refinement using Rosetta. Proteins 77:89–99
SantaLucia J Jr (1998) A unified view of polymer, dumbbell, and oligonucleotide DNA nearest-neighbor thermodynamics. Proc Natl Acad Sci USA 95:1460–1465
SantaLucia J Jr, Hicks D (2004) The thermodynamics of DNA structural motifs. Annu Rev Biophys Biomol Struct 33:413–438
Sayle RA, Milner-White EJ (1995) RASMOL: biomolecular graphics for all. Trends Biochem Sci 20:374
Sclavi B, Woodson S, Sullivan M, Chance MR, Brenowitz M (1997) Time-resolved synchrotron X-ray “footprinting”, a new approach to the study of nucleic acid structure and function: application to protein-DNA interactions and RNA folding. J Mol Biol 266:144–159
Shapiro BA, Yingling YG, Kasprzak W, Bindewald E (2007) Bridging the gap in RNA structure prediction. Curr Opin Struct Biol 17:157–165
Sherman WB, Seeman NC (2006) Design of minimally strained nucleic Acid nanotubes. Biophys J 90:4546–4557
Tan RKZ, Petrov AS, Harvey SC (2006) YUP: a molecular simulation program for coarse-grained and multiscaled models. J Chem Theor Comput 2:529–540
Taylor DJ, Devkota B, Huang AD, Topf M, Narayanan E, Sali A, Harvey SC, Frank J (2009) Comprehensive molecular structure of the eukaryotic ribosome. Structure 17:1591–1604
Tinoco I Jr, Bustamante C (1999) How RNA folds. J Mol Biol 293:271–281
Tsai H-Y, Masquida B, Biswas R, Westhof E, Gopalan V (2003) Molecular modeling of the three-dimensional structure of the bacterial RNase P holoenzyme. J Mol Biol 325:661–675
Turner DH, Mathews DH (2010) NNDB: the nearest neighbor parameter database for predicting stability of nucleic acid secondary structure. Nucleic Acids Res 38:D280–282
Turner DH, Sugimoto N, Freier SM (1988) RNA structure prediction. Annu Rev Biophys Biophys Chem 17:167–192
Vaguine AA, Richelle J, Wodak SJ (1999) SFCHECK: a unified set of procedures for evaluating the quality of macromolecular structure-factor data and their agreement with the atomic model. Acta Crystallogr D Biol Crystallogr 55:191–205
Wheeler DL, Barrett T, Benson DA, Bryant SH, Canese K, Chetvernin V, Church DM, DiCuccio M, Edgar R, Federhen S et al (2007) Database resources of the national center for biotechnology information. Nucleic Acids Res 35:D5–12
Word JM, Lovell SC, Richardson JS, Richardson DC (1999) Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation. J Mol Biol 285:1735–1747
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 base pairs. Biochemistry 37:14719–14735
Zhou H, Vermeulen A, Jucker FM, Pardi A (2000) Incorporating residual dipolar couplings into the NMR solution structure determination of nucleic acids. Biopolymers 52:168–180
Zuker M (1989) On finding all suboptimal foldings of an RNA molecule. Science 244:48–52
Zuker M, Sankoff D (1984) RNA secondary structures and their prediction. Bull Math Biol 46:591–621
Zweib C, Muller F (1997) Three-dimensional comparative modeling of RNA. Nucleic Acids Symp Ser 36:69–71
Acknowledgments
We thank Norm Watkins for managing NIH grant R44GM085889 and Astrid Tuin for preparing Fig. 6.8. This work was supported by NIH grants R01-GM073179 (P.I. John SantaLucia), U01-AI061192 (P.I. Philip Cunningham), and R44GM085889 (P.I. Norman E. Watkins, Jr., and Fredrick Sijenyi).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Sijenyi, F. et al. (2012). The RNA Folding Problems: Different Levels of sRNA Structure Prediction. In: Leontis, N., Westhof, E. (eds) RNA 3D Structure Analysis and Prediction. Nucleic Acids and Molecular Biology, vol 27. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25740-7_6
Download citation
DOI: https://doi.org/10.1007/978-3-642-25740-7_6
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-25739-1
Online ISBN: 978-3-642-25740-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)