| MLÝNSKÝ, Vojtěch, Pavel BANÁŠ, Nils G. WALTER, Jiří ŠPONER and 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, vol. 115, No 47, p. 13911-13924. ISSN 1520-6106. Available from: https://dx.doi.org/10.1021/jp206963g. |
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@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 = {http://dx.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 and 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, vol.~115, No~47, p.~13911-13924. ISSN~1520-6106. Available from: https://dx.doi.org/10.1021/jp206963g.
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