10.1021/bi100142y.s001
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
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Robust_and_Generic_RNA_Modeling_Using_Inferred_Constraints_A_Structure_for_the_Hepatitis_C_Virus_IRES_Pseudoknot_Domain/2758558
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.