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@article{1139175,
author = {Havrila, Marek and Réblová, Kamila and Zirbel, C. and Leontis, Neocles B. and Šponer, Jiří},
article_location = {New York},
article_number = {46},
doi = {http://dx.doi.org/10.1021/jp408530w},
keywords = {sarcin; isosteric; nonisosteric; RNA},
language = {eng},
issn = {1520-6106},
journal = {Journal of Physical Chemistry B},
title = {Isosteric and Nonisosteric Base Pairs in RNA Motifs: Molecular Dynamics and Bioinformatics Study of the Sarcin-Ricin Internal Loop},
volume = {117},
year = {2013}
}
TY - JOUR
ID - 1139175
AU - Havrila, Marek - Réblová, Kamila - Zirbel, C. - Leontis, Neocles B. - Šponer, Jiří
PY - 2013
TI - Isosteric and Nonisosteric Base Pairs in RNA Motifs: Molecular Dynamics and Bioinformatics Study of the Sarcin-Ricin Internal Loop
JF - Journal of Physical Chemistry B
VL - 117
IS - 46
SP - 14302-14319
EP - 14302-14319
PB - American Chemical Society
SN - 15206106
KW - sarcin
KW - isosteric
KW - nonisosteric
KW - RNA
N2 - The sarcin-ricin RNA motif (SR motif) is one of the most prominent recurrent RNA building blocks that occurs in many different RNA contexts and folds autonomously, that is, in a context-independent manner. In this study, we combined bioinformatics analysis with explicit-solvent molecular dynamics (MD) simulations to better understand the relation between the RNA sequence and the evolutionary patterns of the SR motif. A SHAPE probing experiment was also performed to confirm the fidelity of the MD simulations. We identified 57 instances of the SR motif in a nonredundant subset of the RNA X-ray structure database and analyzed their base pairing, base-phosphate, and backbone-backbone interactions. We extracted sequences aligned to these instances from large rRNA alignments to determine the frequency of occurrence for different sequence variants. We then used a simple scoring scheme based on isostericity to suggest 10 sequence variants with a highly variable expected degree of compatibility with the SR motif 3D structure. We carried out MD simulations of SR motifs with these base substitutions. Nonisosteric base substitutions led to unstable structures, but so did isosteric substitutions which were unable to make key base-phosphate interactions. The MD technique explains why some potentially isosteric SR motifs are not realized during evolution. We also found that the inability to form stable cWW geometry is an important factor in the case of the first base pair of the flexible region of the SR motif. A comparison of structural, bioinformatics, SHAPE probing, and MD simulation data reveals that explicit solvent MD simulations neatly reflect the viability of different sequence variants of the SR motif. Thus, MD simulations can efficiently complement bioinformatics tools in studies of conservation patterns of RNA motifs and provide atomistic insight into the role of their different signature interactions.
ER -
HAVRILA, Marek, Kamila RÉBLOVÁ, C. ZIRBEL, Neocles B. LEONTIS a Jiří ŠPONER. Isosteric and Nonisosteric Base Pairs in RNA Motifs: Molecular Dynamics and Bioinformatics Study of the Sarcin-Ricin Internal Loop. Online. \textit{Journal of Physical Chemistry B}. New York: American Chemical Society, 2013, roč.~117, č.~46, s.~14302-14319. ISSN~1520-6106. Dostupné z: https://dx.doi.org/10.1021/jp408530w. [citováno 2024-04-23]
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