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@article{1839657,
author = {Zhang, Zhengyue and Vogele, J. and Mráziková, Klaudia and Kruse, H. and Cang, X.H. and Wohnert, J. and Krepl, M. and Šponer, Jiří},
article_location = {Washington, D.C.},
article_number = {3},
doi = {http://dx.doi.org/10.1021/acs.jpcb.0c10192},
keywords = {Magnetic Resonance Spectroscopy; Molecular Dynamics Simulation; Phosphates; RNA},
language = {eng},
issn = {1520-6106},
journal = {Journal of Physical Chemistry B},
title = {Phosphorothioate Substitutions in RNA Structure Studied by Molecular Dynamics Simulations, QM/MM Calculations, and NMR Experiments},
url = {https://pubs.acs.org/doi/10.1021/acs.jpcb.0c10192},
volume = {125},
year = {2021}
}
TY - JOUR
ID - 1839657
AU - Zhang, Zhengyue - Vogele, J. - Mráziková, Klaudia - Kruse, H. - Cang, X.H. - Wohnert, J. - Krepl, M. - Šponer, Jiří
PY - 2021
TI - Phosphorothioate Substitutions in RNA Structure Studied by Molecular Dynamics Simulations, QM/MM Calculations, and NMR Experiments
JF - Journal of Physical Chemistry B
VL - 125
IS - 3
SP - 825-840
EP - 825-840
PB - American Chemical Society
SN - 15206106
KW - Magnetic Resonance Spectroscopy
KW - Molecular Dynamics Simulation
KW - Phosphates
KW - RNA
UR - https://pubs.acs.org/doi/10.1021/acs.jpcb.0c10192
N2 - Phosphorothioates (PTs) are important chemical modifications of the RNA backbone where a single nonbridging oxygen of the phosphate is replaced with a sulfur atom. PT can stabilize RNAs by protecting them from hydrolysis and is commonly used as a tool to explore their function. It is, however, unclear what basic physical effects PT has on RNA stability and electronic structure. Here, we present molecular dynamics (MD) simulations, quantum mechanical (QM) calculations, and NMR spectroscopy measurements, exploring the effects of PT modifications in the structural context of the neomycinsensing riboswitch (NSR). The NSR is the smallest biologically functional riboswitch with a well-defined structure stabilized by a U-turn motif. Three of the signature interactions of the U-turn: an H-bond, an anion- pi interaction, and a potassium binding site; are formed by RNA phosphates, making the NSR an ideal model for studying how PT affects RNA structure and dynamics. By comparing with high-level QM calculations, we reveal the distinct physical properties of the individual interactions facilitated by the PT. The sulfur substitution, besides weakening the direct H-bond interaction, reduces the directionality of H-bonding while increasing its dispersion and induction components. It also reduces the induction and increases the dispersion component of the anion-pi stacking. The sulfur force-field parameters commonly employed in the literature do not reflect these distinctions, leading to the unsatisfactory description of PT in simulations of the NSR. We show that it is not possible to accurately describe the PT interactions using one universal set of van der Waals sulfur parameters and provide suggestions for improving the force-field performance.
ER -
ZHANG, Zhengyue, J. VOGELE, Klaudia MRÁZIKOVÁ, H. KRUSE, X.H. CANG, J. WOHNERT, M. KREPL and Jiří ŠPONER. Phosphorothioate Substitutions in RNA Structure Studied by Molecular Dynamics Simulations, QM/MM Calculations, and NMR Experiments. \textit{Journal of Physical Chemistry B}. Washington, D.C.: American Chemical Society, 2021, vol.~125, No~3, p.~825-840. ISSN~1520-6106. Available from: https://dx.doi.org/10.1021/acs.jpcb.0c10192.
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