Phosphorothioate Substitutions in RNA Structure Studied by Molecular Dynamics Simulations, QM/MM Calculations, and NMR Experiments
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00541887" target="_blank" >RIV/68081707:_____/21:00541887 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00216224:14740/21:00124372
Výsledek na webu
<a href="https://pubs.acs.org/doi/10.1021/acs.jpcb.0c10192" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jpcb.0c10192</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jpcb.0c10192" target="_blank" >10.1021/acs.jpcb.0c10192</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Phosphorothioate Substitutions in RNA Structure Studied by Molecular Dynamics Simulations, QM/MM Calculations, and NMR Experiments
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Phosphorothioate Substitutions in RNA Structure Studied by Molecular Dynamics Simulations, QM/MM Calculations, and NMR Experiments
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10403 - Physical chemistry
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2021
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Journal of Physical Chemistry B
ISSN
1520-6106
e-ISSN
1520-5207
Svazek periodika
125
Číslo periodika v rámci svazku
3
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
16
Strana od-do
825-840
Kód UT WoS článku
000614308000014
EID výsledku v databázi Scopus
2-s2.0-85100243042