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ModeRNA: a tool for comparative modeling of RNA 3D structure.

Rother M, Rother K, Puton T, Bujnicki JM - Nucleic Acids Res. (2011)

Bottom Line: It must be emphasized that a good alignment is required for successful modeling, and for large and complex RNA molecules the development of a good alignment usually requires manual adjustments of the input data based on previous expertise of the respective RNA family.It is equipped with many functions for merging fragments of different nucleic acid structures into a single model and analyzing their geometry.Windows and UNIX implementations of ModeRNA with comprehensive documentation and a tutorial are freely available.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, ul Ks Trojdena 4, 02-109 Warsaw, Poland.

ABSTRACT
RNA is a large group of functionally important biomacromolecules. In striking analogy to proteins, the function of RNA depends on its structure and dynamics, which in turn is encoded in the linear sequence. However, while there are numerous methods for computational prediction of protein three-dimensional (3D) structure from sequence, with comparative modeling being the most reliable approach, there are very few such methods for RNA. Here, we present ModeRNA, a software tool for comparative modeling of RNA 3D structures. As an input, ModeRNA requires a 3D structure of a template RNA molecule, and a sequence alignment between the target to be modeled and the template. It must be emphasized that a good alignment is required for successful modeling, and for large and complex RNA molecules the development of a good alignment usually requires manual adjustments of the input data based on previous expertise of the respective RNA family. ModeRNA can model post-transcriptional modifications, a functionally important feature analogous to post-translational modifications in proteins. ModeRNA can also model DNA structures or use them as templates. It is equipped with many functions for merging fragments of different nucleic acid structures into a single model and analyzing their geometry. Windows and UNIX implementations of ModeRNA with comprehensive documentation and a tutorial are freely available.

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The model of Azoarcus group I intron built with ModeRNA (in red) and with RNABuilder (51) (in blue) compared with the experimentally solved structure, PDB code 1U6B (in green).
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Figure 5: The model of Azoarcus group I intron built with ModeRNA (in red) and with RNABuilder (51) (in blue) compared with the experimentally solved structure, PDB code 1U6B (in green).

Mentions: We also constructed a model of the Azoarcus group I intron, to enable comparison with a model of the same molecule generated by the RNAbuilder program described in a recent publication by the Altman group (51). A pairwise alignment of the Twort group I intron template structure (1Y0Q_A) and the target sequence (corresponding to 1U6B) was created according to the description in the mentioned article. A first model with an overall RMSD of 6.9 could be built using ModeRNA standard, naïve mode of operation (one template + target–template alignment → model). Subsequently, we used the scripting interface to model the L9/P5 and L2/P8 tertiary loop interactions using the Tetrahymena intron as an additional template, according to the description of the advanced modeling protocol used for modeling by the Altman group. With these additional commands, the accuracy of the model generated with ModeRNA improves significantly, with the RMSD reaching 4.3 Å for the whole structure, and 2.0 Å for the core. These values compare favorably with the RMSD of 4.4 and 2.7 (entire model and the core alone) calculated for the model created by RNABuilder. The model and the experimentally solved structure are presented in Figure 5 and the detailed RMSD values comparison between the ModeRNA and the RNABuilder models are shown in Supplementary Table S1. The RMSD values for both models were obtained with the same script, which is available on request. We conclude that the lack of a sophisticated ‘folding simulation’ procedure for model refinement in ModeRNA does not prevent it from building accurate models. On the other hand, using multiple templates and utilizing the advanced mode of ModeRNA can significantly improve the accuracy, compared to modeling based on a single template.Figure 5.


ModeRNA: a tool for comparative modeling of RNA 3D structure.

Rother M, Rother K, Puton T, Bujnicki JM - Nucleic Acids Res. (2011)

The model of Azoarcus group I intron built with ModeRNA (in red) and with RNABuilder (51) (in blue) compared with the experimentally solved structure, PDB code 1U6B (in green).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3105415&req=5

Figure 5: The model of Azoarcus group I intron built with ModeRNA (in red) and with RNABuilder (51) (in blue) compared with the experimentally solved structure, PDB code 1U6B (in green).
Mentions: We also constructed a model of the Azoarcus group I intron, to enable comparison with a model of the same molecule generated by the RNAbuilder program described in a recent publication by the Altman group (51). A pairwise alignment of the Twort group I intron template structure (1Y0Q_A) and the target sequence (corresponding to 1U6B) was created according to the description in the mentioned article. A first model with an overall RMSD of 6.9 could be built using ModeRNA standard, naïve mode of operation (one template + target–template alignment → model). Subsequently, we used the scripting interface to model the L9/P5 and L2/P8 tertiary loop interactions using the Tetrahymena intron as an additional template, according to the description of the advanced modeling protocol used for modeling by the Altman group. With these additional commands, the accuracy of the model generated with ModeRNA improves significantly, with the RMSD reaching 4.3 Å for the whole structure, and 2.0 Å for the core. These values compare favorably with the RMSD of 4.4 and 2.7 (entire model and the core alone) calculated for the model created by RNABuilder. The model and the experimentally solved structure are presented in Figure 5 and the detailed RMSD values comparison between the ModeRNA and the RNABuilder models are shown in Supplementary Table S1. The RMSD values for both models were obtained with the same script, which is available on request. We conclude that the lack of a sophisticated ‘folding simulation’ procedure for model refinement in ModeRNA does not prevent it from building accurate models. On the other hand, using multiple templates and utilizing the advanced mode of ModeRNA can significantly improve the accuracy, compared to modeling based on a single template.Figure 5.

Bottom Line: It must be emphasized that a good alignment is required for successful modeling, and for large and complex RNA molecules the development of a good alignment usually requires manual adjustments of the input data based on previous expertise of the respective RNA family.It is equipped with many functions for merging fragments of different nucleic acid structures into a single model and analyzing their geometry.Windows and UNIX implementations of ModeRNA with comprehensive documentation and a tutorial are freely available.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, ul Ks Trojdena 4, 02-109 Warsaw, Poland.

ABSTRACT
RNA is a large group of functionally important biomacromolecules. In striking analogy to proteins, the function of RNA depends on its structure and dynamics, which in turn is encoded in the linear sequence. However, while there are numerous methods for computational prediction of protein three-dimensional (3D) structure from sequence, with comparative modeling being the most reliable approach, there are very few such methods for RNA. Here, we present ModeRNA, a software tool for comparative modeling of RNA 3D structures. As an input, ModeRNA requires a 3D structure of a template RNA molecule, and a sequence alignment between the target to be modeled and the template. It must be emphasized that a good alignment is required for successful modeling, and for large and complex RNA molecules the development of a good alignment usually requires manual adjustments of the input data based on previous expertise of the respective RNA family. ModeRNA can model post-transcriptional modifications, a functionally important feature analogous to post-translational modifications in proteins. ModeRNA can also model DNA structures or use them as templates. It is equipped with many functions for merging fragments of different nucleic acid structures into a single model and analyzing their geometry. Windows and UNIX implementations of ModeRNA with comprehensive documentation and a tutorial are freely available.

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