Simulated 18O kinetic isotope effects in enzymatic hydrolysis of guanosine triphosphate

We compare the computed on the base of quantum mechanical-molecular mechanical (QM/MM) modeling kinetic isotope effects (KIEs) for a series of the ¹⁸O-labeled substrates in enzymatic hydrolysis of guanosine triphosphate (GTP) with those measured experimentally. Following the quantitative structure-activity relationship concept, we introduce the correlation between KIEs and structure of substrates with the help of a labeling index, which also aids better imaging of presentation of both experimental and theoretical data. An evident correlation of the computed and measured KIEs provides support to the predominantly dissociative-type reaction mechanism of enzymatic GTP hydrolysis predicted in QM/MM simulations.