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A step or two towards solution of the RNA folding problem
Author(s) -
Brenowitz Michael D,
Laederach Alain,
Mitra Somdeb,
Schlatterer Joerg,
Shcherbakova Inna
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.528.2
Subject(s) - ribozyme , footprinting , chemistry , rna , folding (dsp implementation) , downhill folding , folding funnel , dna footprinting , contact order , hairpin ribozyme , phi value analysis , protein folding , computational biology , crystallography , biology , dna , biochemistry , base sequence , gene expression , promoter , electrical engineering , gene , engineering
The RNA folding problem addresses the question of predicting the three‐dimensional structure of RNA molecules from their nucleotide sequences. It is well known that large RNA molecules may follow multiple pathways with significantly populated intermediate species during folding. Many RNA folding reactions are kinetically controlled. We collect ensembles of time – dependent local changes in solvent accessibility to construct ‘structural – kinetic’ models describing the folding of group I ribozymes. These models define the pathways that dominate folding, the rate constants that govern interconversion of the species present in solution and the structures of the reaction intermediates. The collection of local measures is acquired using ‘Fast Fenton’ footprinting, a laboratory based method for time‐resolved hydroxyl radical footprinting that follows folding with millisecond time and single nucleotide spatial resolution. Clustering of the 25 – 30 individual time – progress curves typically acquired in a Fast Fenton folding experiment and kinetic modeling is carried out using the KinFold software. Folding studies will be presented that utilize solution conditions, perturbation of tertiary contacts and phylogenetic relationships to illuminate the physical character of the individual steps of the group I ribozyme folding reactions. The work to be described in this presentation is supported by grant PO1–GM066275 from the National Institutes of Health.