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Updated: Sep 17, 2025

Time-Resolved Fluorescence Anisotropy from Single Molecules for Characterizing Local Flexibility in Biomolecules
Published on: April 25, 2025
Structural heterogeneity and dynamics in the apical stem loop of s2m from SARS-CoV-2 Delta by an integrative NMR
Maria A Wirtz Martin1, Joseph A Makowski2, Tobias Matzel1
1Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Max-von-Laue-Str. 7, 60438 Frankfurt, Germany.
Abstract:
In structured RNAs, helical elements are often capped by apical loops that are integral structural elements, ranging from 3 to >20 nts of size on average, and display a highly heterogeneous energy landscape profile, rendering structural characterization particularly challenging. We here provide a characterization of the SARS-CoV-2 Delta s2m element containing a highly dynamic nonaloop using an integrative approach of nuclear magnetic resonance spectroscopy (NMR), small angle X-ray scattering (SAXS), and molecular dynamics simulations (MD). We further explored the conformational space in the s2m nonaloop and its transient closing 5'-G-U-3' base pair by MD simulations weighted by experimental NMR observables, leading to a comprehensive representation of the s2m nonaloop motif. Our deconvolution of the ensemble into conformations and dynamics provides a basis for future ensemble-functional characterization of RNA structures featuring dynamic motifs.
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