@article{d806088b396a4bd088e8c5742ff7f1e6,
title = "Insights into the structural stability of major groove RNA triplexes by WAXS-guided MD simulations",
abstract = "RNA triple helices are commonly observed tertiary motifs that are associated with critical biological functions, including signal transduction. Because the recognition of their biological importance is relatively recent, their full range of structural properties has not yet been elucidated. The integration of solution wide-angle X-ray scattering (WAXS) with molecular dynamics (MD) simulations, described here, provides a new way to capture the structures of major-groove RNA triplexes that evade crystallographic characterization. This method yields excellent agreement between measured and computed WAXS profiles and allows for an atomically detailed visualization of these motifs. Using correlation maps, the relationship between well-defined features in the scattering profiles and real space characteristics of RNA molecules is defined, including the subtle conformational variations in the double-stranded RNA upon the incorporation of a third strand by base triples. This readily applicable approach has the potential to provide insight into interactions that stabilize RNA tertiary structure that enables function.",
keywords = "MD simulations, RNA structure, RNA triplex, WAXS, experimentally guided sampling",
author = "Chen, {Yen Lin} and Weiwei He and Serdal Kirmizialtin and Lois Pollack",
note = "Funding Information: This work was supported by NIH grant R35-GM122514 to L.P. Support for work performed at the CBMS beam line LIX (16ID) at NSLS-II is provided by NIH (P30 GM133893, S10 OD012331, and BER- BO 070). NSLS-II is supported by DOE (BES-FWP-PS001). Computational research was carried out on the High Performance Computing resources at New York University Abu Dhabi. S.K. and W.H. are supported by an AD181 faculty research grant. The authors thank Shirish Chodankar and Lin Yang for experimental assistance and Jorge Naranjo for his computational support. Y.-L.C. performed the experiments and analyzed the data. W.H. performed and analyzed the simulations. S.K. and L.P designed the study. All authors contributed to integrating experimental with computational data and to writing the manuscript. The authors declare no competing interests. Funding Information: This work was supported by NIH grant R35-GM122514 to L.P. Support for work performed at the CBMS beam line LIX ( 16ID ) at NSLS-II is provided by NIH ( P30 GM133893 , S10 OD012331 , and BER- BO 070 ). NSLS-II is supported by DOE ( BES-FWP-PS001 ). Computational research was carried out on the High Performance Computing resources at New York University Abu Dhabi . S.K. and W.H. are supported by an AD181 faculty research grant. The authors thank Shirish Chodankar and Lin Yang for experimental assistance and Jorge Naranjo for his computational support. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = jul,
day = "20",
doi = "10.1016/j.xcrp.2022.100971",
language = "English (US)",
volume = "3",
journal = "Cell Reports Physical Science",
issn = "2666-3864",
publisher = "Cell Press",
number = "7",
}