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

J 2011

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

MLÝNSKÝ, Vojtěch; Pavel BANÁŠ; Nils G. WALTER; Jiří ŠPONER; Michal OTYEPKA et al.

Základní údaje

Originální název

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

Autoři

MLÝNSKÝ, Vojtěch; Pavel BANÁŠ; Nils G. WALTER; Jiří ŠPONER a Michal OTYEPKA

Vydání

JOURNAL OF PHYSICAL CHEMISTRY B, Washington, American Chemical Society, 2011, 1520-6106

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10403 Physical chemistry

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.696

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/11:00050558

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1021/jp206963g

UT WoS

000297195400014

Klíčová slova anglicky

TRANSITION-STATE STABILIZATION; BASE-PHOSPHATE INTERACTIONS; DENSITY-FUNCTIONAL THEORY; MATRIX PROPAGATION ADMP; DELTA-VIRUS RIBOZYME; ACTIVE-SITE ADENINE; MOLECULAR-DYNAMICS; STRUCTURAL DYNAMICS; ENZYMATIC-REACTIONS; PHOSPHORYL TRANSFER

Štítky

ok, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 3. 2012 23:50, Olga Křížová

Anotace

V originále

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 similar to 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 nonbridging phosphate oxygen also leads to feasible reaction pathways. Finally, our calculations consider thio-substitutions of one or both nonbridging oxygens of the scissile phosphate and predict that they have only a negligible effect on the reaction barrier, as observed experimentally.

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: CEITEC - central european institute of technology

GD203/09/H046, projekt VaV

Název: Biochemie na rozcestí mezi in silico a in vitro

Investor: Grantová agentura ČR, Biochemie na rozcestí mezi in silico a in vitro

LC06030, projekt VaV

Název: Biomolekulární centrum

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Biomolekulární centrum

Citovat

MLÝNSKÝ, Vojtěch; Pavel BANÁŠ; Nils G. WALTER; Jiří ŠPONER a Michal OTYEPKA. QM/MM Studies of Hairpin Ribozyme Self-Cleavage Suggest the Feasibility of Multiple Competing Reaction Mechanisms. JOURNAL OF PHYSICAL CHEMISTRY B. Washington: American Chemical Society, 2011, roč. 115, č. 47, s. 13911-13924. ISSN 1520-6106. Dostupné z: https://doi.org/10.1021/jp206963g.

@article{975015,
   author = {Mlýnský, Vojtěch and Banáš, Pavel and Walter, Nils G. and Šponer, Jiří and Otyepka, Michal},
   article_location = {Washington},
   article_number = {47},
   doi = {https://doi.org/10.1021/jp206963g},
   keywords = {TRANSITION-STATE STABILIZATION; BASE-PHOSPHATE INTERACTIONS; DENSITY-FUNCTIONAL THEORY; MATRIX PROPAGATION ADMP; DELTA-VIRUS RIBOZYME; ACTIVE-SITE ADENINE; MOLECULAR-DYNAMICS; STRUCTURAL DYNAMICS; ENZYMATIC-REACTIONS; PHOSPHORYL TRANSFER},
   language = {eng},
   issn = {1520-6106},
   journal = {JOURNAL OF PHYSICAL CHEMISTRY B},
   title = {QM/MM Studies of Hairpin Ribozyme Self-Cleavage Suggest the Feasibility of Multiple Competing Reaction Mechanisms},
   url = {http://pubs.acs.org/doi/abs/10.1021/jp206963g},
   volume = {115},
   year = {2011}
}

TY  - JOUR
ID  - 975015
AU  - Mlýnský, Vojtěch - Banáš, Pavel - Walter, Nils G. - Šponer, Jiří - Otyepka, Michal
PY  - 2011
TI  - QM/MM Studies of Hairpin Ribozyme Self-Cleavage Suggest the Feasibility of Multiple Competing Reaction Mechanisms
JF  - JOURNAL OF PHYSICAL CHEMISTRY B
VL  - 115
IS  - 47
SP  - 13911-13924
EP  - 13911-13924
PB  - American Chemical Society
SN  - 15206106
KW  - TRANSITION-STATE STABILIZATION
KW  - BASE-PHOSPHATE INTERACTIONS
KW  - DENSITY-FUNCTIONAL THEORY
KW  - MATRIX PROPAGATION ADMP
KW  - DELTA-VIRUS RIBOZYME
KW  - ACTIVE-SITE ADENINE
KW  - MOLECULAR-DYNAMICS
KW  - STRUCTURAL DYNAMICS
KW  - ENZYMATIC-REACTIONS
KW  - PHOSPHORYL TRANSFER
UR  - http://pubs.acs.org/doi/abs/10.1021/jp206963g
L2  - http://pubs.acs.org/doi/abs/10.1021/jp206963g
N2  - 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 similar to 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 nonbridging phosphate oxygen also leads to feasible reaction pathways. Finally, our calculations consider thio-substitutions of one or both nonbridging oxygens of the scissile phosphate and predict that they have only a negligible effect on the reaction barrier, as observed experimentally.
ER  -

MLÝNSKÝ, Vojtěch; Pavel BANÁŠ; Nils G. WALTER; Jiří ŠPONER a Michal OTYEPKA. QM/MM Studies of Hairpin Ribozyme Self-Cleavage Suggest the Feasibility of Multiple Competing Reaction Mechanisms. \textit{JOURNAL OF PHYSICAL CHEMISTRY B}. Washington: American Chemical Society, 2011, roč.~115, č.~47, s.~13911-13924. ISSN~1520-6106. Dostupné z: https://doi.org/10.1021/jp206963g.

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