title: 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 functional strategy.
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27599-3290, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lavender
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Dokholyan
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Weeks
mesh_terms: D018387:Codon, Initiator; D020285:Cryoelectron Microscopy; D016174:Hepacivirus / Q000235:genetics*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000737:chemistry*; D012367:RNA, Viral / Q000737:chemistry*; D012270:Ribosomes / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
chemical_list: D018387:Codon, Initiator; D012333:RNA, Messenger; D012367:RNA, Viral; D012997:Solvents