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Statistical potentials for hairpin and internal loops improve the accuracy of the predicted RNA structure - PubMed

  • ️Sat Jan 01 2011

Statistical potentials for hairpin and internal loops improve the accuracy of the predicted RNA structure

David P Gardner et al. J Mol Biol. 2011.

Abstract

RNA is directly associated with a growing number of functions within the cell. The accurate prediction of different RNA higher-order structures from their nucleic acid sequences will provide insight into their functions and molecular mechanics. We have been determining statistical potentials for a collection of structural elements that is larger than the number of structural elements determined with experimentally determined energy values. The experimentally derived free energies and the statistical potentials for canonical base-pair stacks are analogous, demonstrating that statistical potentials derived from comparative data can be used as an alternative energetic parameter. A new computational infrastructure-RNA Comparative Analysis Database (rCAD)-that utilizes a relational database was developed to manipulate and analyze very large sequence alignments and secondary-structure data sets. Using rCAD, we determined a richer set of energetic parameters for RNA fundamental structural elements including hairpin and internal loops. A new version of RNAfold was developed to utilize these statistical potentials. Overall, these new statistical potentials for hairpin and internal loops integrated into the new version of RNAfold demonstrated significant improvements in the prediction accuracy of RNA secondary structure.

Copyright © 2011 Elsevier Ltd. All rights reserved.

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Figures

Figure 1
Figure 1

The ranked order of the twenty tetraloop hairpin loops (with any closing canonical base pair) with the highest comparative/potential ratios (red bars) are shown along the x-axis. The C/P ratio for each of these tetraloop hairpin loops is shown on the y-axis. The ratios for tetraloop hairpin loops flanked by any canonical base pair are shown as red bars while the tetraloop hairpin loops flanked by a CG base pair are shown as blue bars. The values are for bacterial 16S rRNA.

Figure 2
Figure 2

RNA secondary structure prediction accuracies for four RNA folding programs: RNAfold, RNAstructure (TURNER04 & TURNER04 plus newer tri- and tetraloop thermodynamic parameters), CONTRAfold, MultiFold and RNAfold using statistical potentials. Results for sixteen RNA molecular classes are divided into a) bacterial 5S rRNA, eukaryotic 5S rRNA, bacterial 16S rRNA, bacterial 23S rRNA, tRNA, eukaryotic 16S rRNA, RNase P A and bacterial SRP; b) U1 spliceosomal RNA, hepatitis C virus internal ribosome entry site (HCV IRES), ykok leader, TPP and SAM riboswitches, iron response element (IRE), HIV type 1 dimerisation initiation site (HIV DIS) and UnaL2 Line 3′ element.

Figure 3
Figure 3

a) Nucleotides in the tetraloop hairpin loops that occur in the comparative structure for a modified Escherichia coli 16S rRNA secondary structure between positions 118 and 241 are colored green. For this figure the E.coli sequence was changed at a few positions to create better examples of potential base pairings that form hairpin loops. Potential tetraloop hairpin loop, as defined by four nucleotides that are closed by two or more canonical base pairs, are colored red. The base pairs flanking the tetraloop hairpin loops are circled and connected with a red line. Nucleotides that are base paired in the comparative structure are connected with a thick black line. b) Nucleotides in the internal loop that occur in our modified Escherichia coli comparative secondary structure between positions 139 and 184 are colored green; b&c) Nucleotides in potential internal loops are colored red and the nucleotides that form a set of base pairs within the potential helix in the internal loop are circled and connected with a red line. Nucleotides that are base paired in the comparative structure are connected with a thick black line.

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