Crumple: A Method for Complete Enumeration of All Possible Pseudoknot-Free RNA Secondary Structures

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dc.contributor.authorSamuel Bleckleyen_US
dc.contributor.authorJonathan W. Stoneen_US
dc.contributor.authorSusan J. Schroederen_US
dc.date.accessioned2015-01-23T17:17:42Z
dc.date.accessioned2016-03-30T15:36:20Z
dc.date.available2015-01-23T17:17:42Z
dc.date.available2016-03-30T15:36:20Z
dc.date.issued2012-12-27en_US
dc.descriptionThe computing for this project was performed at the OU Supercomputing Center for Education & Research (OSCER) at the University of Oklahoma (OU). OSCER director Henry Neeman and OSCER staff provided valuable technical expertise. The authors acknowledge and appreciate the discussions about this work with Dr. Changwook Kim, Adam Heck, Sean Lavelle, and Jui-wen Liu.en_US
dc.descriptionConceived and designed the experiments: SB SJS. Performed the experiments: SB JWS. Analyzed the data: SB JWS SJS. Wrote the paper: SB JWS SJS.en_US
dc.description.abstractThe diverse landscape of RNA conformational space includes many canyons and crevices that are distant from the lowest minimum free energy valley and remain unexplored by traditional RNA structure prediction methods. A complete description of the entire RNA folding landscape can facilitate identification of biologically important conformations. The Crumple algorithm rapidly enumerates all possible non-pseudoknotted structures for an RNA sequence without consideration of thermodynamics while filtering the output with experimental data. The Crumple algorithm provides an alternative approach to traditional free energy minimization programs for RNA secondary structure prediction. A complete computation of all non-pseudoknotted secondary structures can reveal structures that would not be predicted by methods that sample the RNA folding landscape based on thermodynamic predictions. The free energy minimization approach is often successful but is limited by not considering RNA tertiary and protein interactions and the possibility that kinetics rather than thermodynamics determines the functional RNA fold. Efficient parallel computing and filters based on experimental data make practical the complete enumeration of all non-pseudoknotted structures. Efficient parallel computing for Crumple is implemented in a ring graph approach. Filters for experimental data include constraints from chemical probing of solvent accessibility, enzymatic cleavage of paired or unpaired nucleotides, phylogenetic covariation, and the minimum number and lengths of helices determined from crystallography or cryo-electron microscopy. The minimum number and length of helices has a significant effect on reducing conformational space. Pairing constraints reduce conformational space more than single nucleotide constraints. Examples with Alfalfa Mosaic Virus RNA and Trypanosome brucei guide RNA demonstrate the importance of evaluating all possible structures when pseduoknots, RNA-protein interactions, and metastable structures are important for biological function. Crumple software is freely available at http://adenosine.chem.ou.edu/software.html.en_US
dc.description.peerreviewYesen_US
dc.description.peerreviewnoteshttp://www.plosone.org/static/editorial#peeren_US
dc.identifier.citationBleckley S, Stone JW, Schroeder SJ (2012) Crumple: A Method for Complete Enumeration of All Possible Pseudoknot-Free RNA Secondary Structures. PLoS ONE 7(12): e52414. doi:10.1371/journal.pone.0052414en_US
dc.identifier.doi10.1371/journal.pone.0052414en_US
dc.identifier.urihttp://hdl.handle.net/11244/14086
dc.language.isoen_USen_US
dc.publisherPLos Oneen_US
dc.relation.ispartofseriesPLoS ONE 7(12):e52414en_US
dc.relation.urihttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0052414en_US
dc.rightsAttribution 3.0 United Statesen_US
dc.rights.requestablefalseen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/en_US
dc.subjectPLOSen_US
dc.subjectPublic Library of Scienceen_US
dc.subjectOpen Accessen_US
dc.subjectOpen-Accessen_US
dc.subjectScienceen_US
dc.subjectMedicineen_US
dc.subjectBiologyen_US
dc.subjectResearchen_US
dc.subjectPeer-reviewen_US
dc.subjectInclusiveen_US
dc.subjectInterdisciplinaryen_US
dc.subjectAnte-disciplinaryen_US
dc.subjectPhysicsen_US
dc.subjectChemistryen_US
dc.subjectEngineeringen_US
dc.titleCrumple: A Method for Complete Enumeration of All Possible Pseudoknot-Free RNA Secondary Structuresen_US
dc.typeResearch Articleen_US

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