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 journalArticle

25 Citations (Scopus)

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

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Viruses
Hepacivirus
RNA
Molecular Mimicry
Cryoelectron Microscopy
Initiator Codon
Molecular Dynamics Simulation
Bioinformatics
Transfer RNA
Computational Biology
Electron microscopy
Molecular dynamics
Nucleotides
Messenger RNA
Internal Ribosome Entry Sites

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

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Robust and generic RNA modeling using inferred constraints : A structure for the hepatitis C virus IRES pseudoknot domain. / Lavender, Christopher A.; Ding, Feng; Dokholyan, Nikolay V.; Weeks, Kevin M.

In: Biochemistry, Vol. 49, No. 24, 22.06.2010, p. 4931-4933.

Research output: Contribution to journalArticle

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