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1.  Three-Dimensional RNA Structure Refinement by Hydroxyl Radical Probing 
Nature methods  2012;9(6):603-608.
Molecular modeling guided by experimentally-derived structural information is an attractive approach for three-dimensional structure determination of complex RNAs that are not amenable to study by high-resolution methods. Hydroxyl radical probing (HRP), performed routinely in many laboratories, provides a measure of solvent accessibility at individual nucleotides. HRP measurements have, to date, only been used to evaluate RNA models qualitatively. Here, we report development of a quantitative structure refinement approach using HRP measurements to drive discrete molecular dynamics simulations for RNAs ranging in size from 80 to 230 nucleotides. HRP reactivities were first used to identify RNAs that form extensive helical packing interactions. For these RNAs, we achieved highly significant structure predictions, given inputs of RNA sequence and base pairing. This HRP-directed tertiary structure refinement approach generates robust structural hypotheses useful for guiding explorations of structure-function interrelationships in RNA.
doi:10.1038/nmeth.1976
PMCID: PMC3422565  PMID: 22504587
2.  Robust and Generic RNA Modeling Using Inferred Constraints: A Structure for the Hepatitis C Virus IRES Pseudoknot Domain 
Biochemistry  2010;49(24):4931-4933.
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 (DMD)-based modeling system that uses long-range constraints inferred from diverse biochemical or bioinformatic analyses to create statistically significant (p < 0.01) native-like folds for RNAs of known structure ranging from 45 to 158 nucleotides. We then predict the unknown structure of the hepatitis C virus IRES pseudoknot domain. The resulting RNA model rationalizes independent solvent accessibility and cryo-electron microscopy structure information. The pseudoknot positions the AUG start codon near the mRNA channel and is tRNA-like, suggesting the IRES employs molecular mimicry as a functional strategy.
doi:10.1021/bi100142y
PMCID: PMC2889920  PMID: 20545364

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