Recognition of 2 ',5 '-linked oligoadenylates by human ribonuclease L: molecular dynamics study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F14%3A10287783" target="_blank" >RIV/00216208:11320/14:10287783 - isvavai.cz</a>

Výsledek na webu

<a href="http://link.springer.com/article/10.1007%2Fs00894-014-2123-x" target="_blank" >http://link.springer.com/article/10.1007%2Fs00894-014-2123-x</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00894-014-2123-x" target="_blank" >10.1007/s00894-014-2123-x</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Recognition of 2 ',5 '-linked oligoadenylates by human ribonuclease L: molecular dynamics study

Popis výsledku v původním jazyce

The capability of current MD simulations to be used as a tool in rational design of agonists of medically interesting enzyme RNase L was tested. Dimerization and enzymatic activity of RNase L is stimulated by 2',5'-linked oligoadenylates (pA(25)A(25)A; 2-5A). First, it was necessary to ensure that a complex of monomeric human RNase L and 25A was stable in MD simulations. It turned out that Glu131 had to be protonated. The non-protonated Glu131 caused dissociation of 2-5A from RNase L. Because of the atypical 2'-5' internucleotide linkages and a specific spatial arrangement of the 25A trimer, when a single molecule carries all possible conformers of the glycosidic torsion angle, several versions of the AMBER force field were tested. One that best maintained functionally important interactions of 25A and RNase L was selected for subsequent MD simulations. Furthermore, we wonder whether powerful GPUs are able to produce MD trajectories long enough to convincingly demonstrate effects of su

Název v anglickém jazyce

Recognition of 2 ',5 '-linked oligoadenylates by human ribonuclease L: molecular dynamics study

Popis výsledku anglicky

The capability of current MD simulations to be used as a tool in rational design of agonists of medically interesting enzyme RNase L was tested. Dimerization and enzymatic activity of RNase L is stimulated by 2',5'-linked oligoadenylates (pA(25)A(25)A; 2-5A). First, it was necessary to ensure that a complex of monomeric human RNase L and 25A was stable in MD simulations. It turned out that Glu131 had to be protonated. The non-protonated Glu131 caused dissociation of 2-5A from RNase L. Because of the atypical 2'-5' internucleotide linkages and a specific spatial arrangement of the 25A trimer, when a single molecule carries all possible conformers of the glycosidic torsion angle, several versions of the AMBER force field were tested. One that best maintained functionally important interactions of 25A and RNase L was selected for subsequent MD simulations. Furthermore, we wonder whether powerful GPUs are able to produce MD trajectories long enough to convincingly demonstrate effects of su

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

BO - Biofyzika

OECD FORD obor

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Projekt

<a href="/cs/project/GA13-26526S" target="_blank" >GA13-26526S: Nové DNA a RNA oligonukleotidy s fosfonothioátovými a fosfonoamidátovými internukleotidovými vazbami</a><br>

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Molecular Modeling

ISSN

1610-2940

e-ISSN

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Svazek periodika

2014

Číslo periodika v rámci svazku

20

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

19

Strana od-do

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Kód UT WoS článku

000334934900033

EID výsledku v databázi Scopus

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