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

Christopher A. Lavender, Feng Ding, Nikolay V. Dokholyan, Kevin M. Weeks

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4931-4933
Number of pages3
JournalBiochemistry
Volume49
Issue number24
DOIs
StatePublished - Jun 22 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry

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