%0 Generic %A Lavender, Christopher A. %A Ding, Feng %A Dokholyan, Nikolay V. %A Weeks, Kevin M. %D 2010 %T Robust and Generic RNA Modeling Using Inferred Constraints: A Structure for the Hepatitis C Virus IRES Pseudoknot Domain %U https://acs.figshare.com/articles/dataset/Robust_and_Generic_RNA_Modeling_Using_Inferred_Constraints_A_Structure_for_the_Hepatitis_C_Virus_IRES_Pseudoknot_Domain/2758555 %R 10.1021/bi100142y.s002 %2 https://acs.figshare.com/ndownloader/files/4451533 %K Inferred Constraints %K Hepatitis C Virus IRES Pseudoknot DomainRNA function %K AUG %K bioinformatic analyses %K Generic RNA Modeling %K ribosome entry site %K pseudoknot domain positions %K hepatitis C virus %K 158 nucleotides %K mRNA channel %K RNA model rationalizes %K pseudoknot domain %X 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. %I ACS Publications