Back to Search
Start Over
Native-like RNA tertiary structures using a sequence-encoded cleavage agent and refinement by discrete molecular dynamics
- Source :
- Journal of the American Chemical Society. 131(7)
- Publication Year :
- 2009
-
Abstract
- The difficulty of analyzing higher order RNA structure, especially for folding intermediates and for RNAs whose functions require domains that are conformationally flexible, emphasizes the need for new approaches for modeling RNA tertiary structure accurately. Here, we report a concise approach that makes use of facile RNA structure probing experiments that are then interpreted using a computational algorithm, carefully tailored to optimize both the resolution and refinement speed for the resulting structures, without requiring user intervention. The RNA secondary structure is first established using SHAPE chemistry. We then use a sequence-directed cleavage agent, which can be placed arbitrarily in many helical motifs, to obtain high quality inter-residue distances. We interpret this in-solution chemical information using a fast, coarse grained, discrete molecular dynamics engine in which each RNA nucleotide is represented by pseudoatoms for the phosphate, ribose, and nucleobase groups. By this approach, we refine base paired positions in yeast tRNA(Asp) to 4 A rmsd without any preexisting information or assumptions about secondary or tertiary structures. This blended experimental and computational approach has the potential to yield native-like models for the diverse universe of functionally important RNAs whose structures cannot be characterized by conventional structural methods.
- Subjects :
- Models, Molecular
Molecular Sequence Data
Biochemistry
Ferric Compounds
Catalysis
Article
Nucleic acid secondary structure
Nucleobase
chemistry.chemical_compound
Molecular dynamics
Colloid and Surface Chemistry
Ribose
Ferrous Compounds
Nucleic acid structure
Edetic Acid
RNA, Transfer, Asp
Base Sequence
Nucleic acid tertiary structure
RNA
General Chemistry
Crystallography
chemistry
Transfer RNA
Nucleic Acid Conformation
Biological system
Subjects
Details
- ISSN :
- 15205126
- Volume :
- 131
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Journal of the American Chemical Society
- Accession number :
- edsair.doi.dedup.....38c6f4d006a1e98e39944429948a5fff