Robust and generic RNA modeling using inferred constraints: a structure for the hepatitis C virus IRES pseudoknot domain.

ABSTRACT: 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 fu

SUBMITTER: Lavender CA 

PROVIDER: S-EPMC2889920 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature