Complex between Human RNase HI and the phosphonate-DNA/RNA duplex: Molecular dynamics study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F13%3A10190058" target="_blank" >RIV/00216208:11320/13:10190058 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.jmgm.2013.05.004" target="_blank" >http://dx.doi.org/10.1016/j.jmgm.2013.05.004</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jmgm.2013.05.004" target="_blank" >10.1016/j.jmgm.2013.05.004</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Complex between Human RNase HI and the phosphonate-DNA/RNA duplex: Molecular dynamics study

Popis výsledku v původním jazyce

Our 200 ns MD simulations show that even fully modified oligonucleotides bearing the 3'-O-P-CH2-O-5' (but not 3'-O-CH2-P-O-5') phosphonate linkages can be successfully attached to the surface of Human RNase H. It enables to explain that oligonucleotidesconsisting of the alternating 3'-O-P-CH2-O-5' phosphonate and phosphodiester linkages are capable to elicit the RNase H activity (while the 3'-O-CH2-P-O-5' phosphonates are completely inactive). Stability of the binuclear active site of Human RNase H wasachieved using the one-atom model for Mg2+ in conjunction with a polarized phosphate group of the scissile bond, which is wedged between both magnesium ions. The reference MD simulation (lasting for 1000 ns), which was produced using a well-establishedseven-point (with dummy atoms) model for Mg2+ led to essentially the same results. The MD run (lasting for 500 ns) produced for the Therms thermophilus Argonaute enzyme shows the transferability of our approach for the stabilization of a

Název v anglickém jazyce

Complex between Human RNase HI and the phosphonate-DNA/RNA duplex: Molecular dynamics study

Popis výsledku anglicky

Our 200 ns MD simulations show that even fully modified oligonucleotides bearing the 3'-O-P-CH2-O-5' (but not 3'-O-CH2-P-O-5') phosphonate linkages can be successfully attached to the surface of Human RNase H. It enables to explain that oligonucleotidesconsisting of the alternating 3'-O-P-CH2-O-5' phosphonate and phosphodiester linkages are capable to elicit the RNase H activity (while the 3'-O-CH2-P-O-5' phosphonates are completely inactive). Stability of the binuclear active site of Human RNase H wasachieved using the one-atom model for Mg2+ in conjunction with a polarized phosphate group of the scissile bond, which is wedged between both magnesium ions. The reference MD simulation (lasting for 1000 ns), which was produced using a well-establishedseven-point (with dummy atoms) model for Mg2+ led to essentially the same results. The MD run (lasting for 500 ns) produced for the Therms thermophilus Argonaute enzyme shows the transferability of our approach for the stabilization of a

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/GA202%2F09%2F0193" target="_blank" >GA202/09/0193: Vznik a dynamika strukturních motivů nukleových kyselin podílejících se na regulaci genové exprese</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2013

Kód důvěrnosti údajů

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

Název periodika

Journal of Molecular Graphics and Modelling

ISSN

1093-3263

e-ISSN

—

Svazek periodika

44

Číslo periodika v rámci svazku

červenec

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

81-90

Kód UT WoS článku

000324965300009

EID výsledku v databázi Scopus

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