Recent Research Developments
|Index of Recent Research News|
July 21, 2004
Insight into the mechanism of RNA
catalysis holds promise in the design of new medical therapies that
target genetic disorders as well as the development of new
biotechnology. One experimental method used to probe the
mechanism of RNA enzymes is the measurement of so-called thio effects:
the change in reaction rate that occurs upon substitution of key
phosphoryl oxygen positions with
sulfur. The mechanstic interpretation of experimental thio
effects, however, is often ambiguous. Theoretical methods offer a
powerful tool to aid in the mechanistic interpretation of experimental
thio effects and provide additional insight into the chemical reaction
Recently, graduate student Brent Gregersen and Professor Darrin York of the Department of Chemistry, in collaboration with MSI research scholar Prof. Xabier Lopez of the University of the Basque Country, reported results of a series of activated dynamics simulations of thio effects on the transesterification reaction of an RNA sugar-phosphate model in solution (Fig. 1).
|Figure 1: In-line
dianionic mechanism of
|The simulations employed a new combined quantum mechanical/molecular mechanical approach, with rigorous treatment of electrostatic interactions, to determine the reaction free energy profiles in solution (Fig. 2a). The change in solvent structure as a function of the reaction coordinate provides a detailed microscopic picture of the role of solvent in the reactions (Fig. 2b). These results are of fundamental biological importance and have been published in a recent issue of the Journal of the American Chemical Society [JACS, 126, 7504 (2004)]. Results of this work can be compared to those contained in QCRNA, a new on-line database of high-level quantum chemical data for RNA catalysis developed by the York Group.|
|Figure 2: (a)
Free energy profiles for native and thio-substituted
transphosphorylation reactions. (b)
Radial distribution of water oxygens (OW) around phosphorus
(P) at the transition state.
| * This page is updated every two
Next scheduled update: Aug. 6, 2004.
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