QM/MM Studies of Hairpin Ribozyme Self-Cleavage Suggest the Feasibility of Multiple Competing Reaction Mechanisms

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F11%3A33118089" target="_blank" >RIV/61989592:15310/11:33118089 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/11:00050558 RIV/68081707:_____/11:00440900

Výsledek na webu

<a href="http://dx.doi.org/10.1021/jp206963g" target="_blank" >http://dx.doi.org/10.1021/jp206963g</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jp206963g" target="_blank" >10.1021/jp206963g</a>

Jazyk výsledku

angličtina

Název v původním jazyce

QM/MM Studies of Hairpin Ribozyme Self-Cleavage Suggest the Feasibility of Multiple Competing Reaction Mechanisms

Popis výsledku v původním jazyce

The hairpin ribozyme is a prominent member of small ribozymes since it does not require metal ions to achieve catalysis. Guanine 8 (G8) and adenine 38 (A38) have been identified as key participants in self-cleavage and -ligation. We have carried out hybrid quantum-mechanical/molecular mechanical (QM/MM) calculations to evaluate the energy along several putative reaction pathways. The error of our DFT description of the QM region was tested and shown to be ~1 kcal/mol. We find that self-cleavage of the hairpin ribozyme may follow several competing microscopic reaction mechanisms, all with calculated activation barriers in good agreement with those from experiment (20-21 kcal/mol). The initial nucleophilic attack of the A-1(2'-OH) group on the scissile phosphate is predicted to be rate-limiting in all these mechanisms. An unprotonated G8- (together with A38H+) yields a feasible activation barrier (20.4 kcal/mol). Proton transfer to a non-bridging phosphate oxygen also leads to feasible r

Název v anglickém jazyce

QM/MM Studies of Hairpin Ribozyme Self-Cleavage Suggest the Feasibility of Multiple Competing Reaction Mechanisms

Popis výsledku anglicky

The hairpin ribozyme is a prominent member of small ribozymes since it does not require metal ions to achieve catalysis. Guanine 8 (G8) and adenine 38 (A38) have been identified as key participants in self-cleavage and -ligation. We have carried out hybrid quantum-mechanical/molecular mechanical (QM/MM) calculations to evaluate the energy along several putative reaction pathways. The error of our DFT description of the QM region was tested and shown to be ~1 kcal/mol. We find that self-cleavage of the hairpin ribozyme may follow several competing microscopic reaction mechanisms, all with calculated activation barriers in good agreement with those from experiment (20-21 kcal/mol). The initial nucleophilic attack of the A-1(2'-OH) group on the scissile phosphate is predicted to be rate-limiting in all these mechanisms. An unprotonated G8- (together with A38H+) yields a feasible activation barrier (20.4 kcal/mol). Proton transfer to a non-bridging phosphate oxygen also leads to feasible r

Druh

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

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

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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)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2011

Kód důvěrnosti údajů

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

Název periodika

Journal of Physical Chemistry B

ISSN

1520-6106

e-ISSN

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Svazek periodika

115

Číslo periodika v rámci svazku

47

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

13911-13924

Kód UT WoS článku

000297195400014

EID výsledku v databázi Scopus

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