10.1021/bi100142y.s002 Christopher A. Lavender Christopher A. Lavender Feng Ding Feng Ding Nikolay V. Dokholyan Nikolay V. Dokholyan Kevin M. Weeks Kevin M. Weeks Robust and Generic RNA Modeling Using Inferred Constraints: A Structure for the Hepatitis C Virus IRES Pseudoknot Domain American Chemical Society 2010 Inferred Constraints Hepatitis C Virus IRES Pseudoknot DomainRNA function AUG bioinformatic analyses Generic RNA Modeling ribosome entry site pseudoknot domain positions hepatitis C virus 158 nucleotides mRNA channel RNA model rationalizes pseudoknot domain 2010-06-22 00:00:00 Dataset 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 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 (<i>p</i> < 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.