Robust and Generic RNA Modeling Using Inferred Constraints: A Structure for the Hepatitis C Virus IRES Pseudoknot Domain
datasetposted on 22.06.2010 by Christopher A. Lavender, Feng Ding, Nikolay V. Dokholyan, Kevin M. Weeks
Datasets usually provide raw data for analysis. This raw data often comes in spreadsheet form, but can be any collection of data, on which analysis can be performed.
RNA function is dependent on its structure, yet three-dimensional folds for most biologically important RNAs are unknown. We develop a generic discrete molecular dynamics-based modeling system that uses long-range constraints inferred from diverse biochemical or bioinformatic analyses to create statistically significant (p < 0.01) nativelike folds for RNAs of known structure ranging from 45 to 158 nucleotides. We then predict the unknown structure of the hepatitis C virus internal ribosome entry site (IRES) pseudoknot domain. The resulting RNA model rationalizes independent solvent accessibility and cryo-electron microscopy structure information. The pseudoknot domain positions the AUG start codon near the mRNA channel and is tRNA-like, suggesting the IRES employs molecular mimicry as a functional strategy.