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@article{1299442,
author = {Estarellas Martin, Carolina and Otyepka, Michal and Koča, Jaroslav and Banáš, Pavel and Krepl, Miroslav and Šponer, Jiří},
article_location = {AMSTERDAM},
article_number = {5},
doi = {http://dx.doi.org/10.1016/j.bbagen.2014.10.021},
keywords = {Cas6 superfamily; Endoribonuclease; RNA cleavage; Protein/RNA complex; Molecular dynamic simulation; Force field},
language = {eng},
issn = {0304-4165},
journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS},
title = {Molecular dynamic simulations of protein/RNA complexes: CRISPR/Csy4 endoribonuclease},
url = {http://ac.els-cdn.com/S0304416514003572/1-s2.0-S0304416514003572-main.pdf?_tid=43e36356-fb15-11e4-8585-00000aab0f27&acdnat=1431703128_b3eaa36f73dde7e7aaacec06315a9df0},
volume = {1850},
year = {2015}
}
TY - JOUR
ID - 1299442
AU - Estarellas Martin, Carolina - Otyepka, Michal - Koča, Jaroslav - Banáš, Pavel - Krepl, Miroslav - Šponer, Jiří
PY - 2015
TI - Molecular dynamic simulations of protein/RNA complexes: CRISPR/Csy4 endoribonuclease
JF - BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
VL - 1850
IS - 5
SP - 1072-1090
EP - 1072-1090
PB - ELSEVIER SCIENCE BV
SN - 03044165
KW - Cas6 superfamily
KW - Endoribonuclease
KW - RNA cleavage
KW - Protein/RNA complex
KW - Molecular dynamic simulation
KW - Force field
UR - http://ac.els-cdn.com/S0304416514003572/1-s2.0-S0304416514003572-main.pdf?_tid=43e36356-fb15-11e4-8585-00000aab0f27&acdnat=1431703128_b3eaa36f73dde7e7aaacec06315a9df0
L2 - http://ac.els-cdn.com/S0304416514003572/1-s2.0-S0304416514003572-main.pdf?_tid=43e36356-fb15-11e4-8585-00000aab0f27&acdnat=1431703128_b3eaa36f73dde7e7aaacec06315a9df0
N2 - Background: Many prokaryotic genomes comprise Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) offering defense against foreign nucleic acids. These immune systems are conditioned by the production of small CRISPR-derived RNAs matured from long RNA precursors. This often requires a Csy4 endoribonuclease cleaving the RNA 3'-end. Methods: We report extended explicit solvent molecular dynamic (MD) simulations of Csy4/RNA complex in precursor and product states, based on X-ray structures of product and inactivated precursor (55 simulations; similar to 3.7 mu s in total). Results: The simulations identify double-protonated His29 and deprotonated terminal phosphate as the likely dominant protonation states consistent with the product structure. We revealed potential substates consistent with Ser148 and His29 acting as the general base and acid, respectively. The Ser148 could be straightforwardly deprotonated through solvent and could without further structural rearrangements deprotonate the nucleophile, contrasting similar studies investigating the general base role of nucleobases in ribozymes. We could not locate geometries consistent with His29 acting as general base. However, we caution that the X-ray structures do not always capture the catalytically active geometries and then the reactive structures may be unreachable by the simulation technique. Conclusions: We identified potential catalytic arrangement of the Csy4/RNA complex but we also report limitations of the simulation technique. Even for the dominant protonation state we could not achieve full agreement between the simulations and the structural data. General significance: Potential catalytic arrangement of the Csy4/RNA complex is found. Further, we provide unique insights into limitations of simulations of protein/RNA complexes, namely, the influence of the starting experimental structures and force field limitations. This article is part of a Special Issue entitled Recent developments of molecular dynamics. (C) 2014 Elsevier B.V. All rights reserved.
ER -
ESTARELLAS MARTIN, Carolina, Michal OTYEPKA, Jaroslav KOČA, Pavel BANÁŠ, Miroslav KREPL a Jiří ŠPONER. Molecular dynamic simulations of protein/RNA complexes: CRISPR/Csy4 endoribonuclease. \textit{BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}. AMSTERDAM: ELSEVIER SCIENCE BV, 2015, roč.~1850, č.~5, s.~1072-1090. ISSN~0304-4165. Dostupné z: https://dx.doi.org/10.1016/j.bbagen.2014.10.021.
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