Integrated NMR/Molecular Dynamics Determination of the Ensemble Conformation of a Thermodynamically Stable CUUG RNA Tetraloop
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Integrated NMR/Molecular Dynamics Determination of the Ensemble Conformation of a Thermodynamically Stable CUUG RNA Tetraloop. / Oxenfarth, Andreas; Kümmerer, Felix; Bottaro, Sandro; Schnieders, Robbin; Pinter, György; Jonker, Hendrik R.A.; Fürtig, Boris; Richter, Christian; Blackledge, Martin; Lindorff-Larsen, Kresten; Schwalbe, Harald.
In: Journal of the American Chemical Society, Vol. 145, No. 30, 2023, p. 16557-16572.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Integrated NMR/Molecular Dynamics Determination of the Ensemble Conformation of a Thermodynamically Stable CUUG RNA Tetraloop
AU - Oxenfarth, Andreas
AU - Kümmerer, Felix
AU - Bottaro, Sandro
AU - Schnieders, Robbin
AU - Pinter, György
AU - Jonker, Hendrik R.A.
AU - Fürtig, Boris
AU - Richter, Christian
AU - Blackledge, Martin
AU - Lindorff-Larsen, Kresten
AU - Schwalbe, Harald
N1 - Publisher Copyright: © 2023 The Authors. Published by American Chemical Society.
PY - 2023
Y1 - 2023
N2 - Both experimental and theoretical structure determinations of RNAs have remained challenging due to the intrinsic dynamics of RNAs. We report here an integrated nuclear magnetic resonance/molecular dynamics (NMR/MD) structure determination approach to describe the dynamic structure of the CUUG tetraloop. We show that the tetraloop undergoes substantial dynamics, leading to averaging of the experimental data. These dynamics are particularly linked to the temperature-dependent presence of a hydrogen bond within the tetraloop. Interpreting the NMR data by a single structure represents the low-temperature structure well but fails to capture all conformational states occurring at a higher temperature. We integrate MD simulations, starting from structures of CUUG tetraloops within the Protein Data Bank, with an extensive set of NMR data, and provide a structural ensemble that describes the dynamic nature of the tetraloop and the experimental NMR data well. We thus show that one of the most stable and frequently found RNA tetraloops displays substantial dynamics, warranting such an integrated structural approach.
AB - Both experimental and theoretical structure determinations of RNAs have remained challenging due to the intrinsic dynamics of RNAs. We report here an integrated nuclear magnetic resonance/molecular dynamics (NMR/MD) structure determination approach to describe the dynamic structure of the CUUG tetraloop. We show that the tetraloop undergoes substantial dynamics, leading to averaging of the experimental data. These dynamics are particularly linked to the temperature-dependent presence of a hydrogen bond within the tetraloop. Interpreting the NMR data by a single structure represents the low-temperature structure well but fails to capture all conformational states occurring at a higher temperature. We integrate MD simulations, starting from structures of CUUG tetraloops within the Protein Data Bank, with an extensive set of NMR data, and provide a structural ensemble that describes the dynamic nature of the tetraloop and the experimental NMR data well. We thus show that one of the most stable and frequently found RNA tetraloops displays substantial dynamics, warranting such an integrated structural approach.
U2 - 10.1021/jacs.3c03578
DO - 10.1021/jacs.3c03578
M3 - Journal article
C2 - 37479220
AN - SCOPUS:85166387855
VL - 145
SP - 16557
EP - 16572
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 30
ER -
ID: 362687227