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Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
Published on: September 21, 2017
The Distinct Structural Propensities of Poly-C, A, and U Single-Stranded RNA
Tong Wang1, Weiwei He2,3, Scout Fronhofer1
1School of Applied and Engineering Physics, Cornell University, Ithaca, New York14853, United States.
Abstract:
Homopolymeric single-stranded RNAs (ssRNAs) are common biological motifs, yet their sequence-dependent solution structures remain incompletely defined. Particularly, rC30 and rA30 have not been characterized with atomic detail. Using optimized force fields, we integrate small-angle X-ray scattering (SAXS) with SAXS-driven molecular dynamics to generate and refine conformational ensembles for thirty-nucleotide-long strands of poly(rA), poly(rC), and poly(rU) (rA30, rC30, and rU30) in identical buffers. Scattering profiles are computed from refined MD-generated ensembles and accurately reproduce the SAXS measurements. Properties of these refined ensembles are further validated by circular dichroism (CD) and UV melting. Clear sequence-dependent order emerges: rA30 is the most compact and helical, rU30 is largely coil-like, and rC30 falls in between. Together, these cross-validated ensembles define distinct conformational propensities of ssRNA homopolymers, specifically highlighting poly(rC) as a unique, moderately structured, yet highly heterogeneous ssRNA. These findings may have implications for nucleotide-specific macromolecular recognition.
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