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. |
Other formats:
BibTeX
LaTeX
RIS
@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.
|