Mechanism of the deceptively simple reaction of guanosine triphosphate (GTP) hydrolysis catalyzed by the cellular protein Ras in complex with the activating protein GAP is an important issue because of the significance of this reaction in cancer research. To prove that the Ras residue Gln61 plays a decisive role in chemical transformations in the enzyme active site, we compare results of quantum mechanics/molecular mechanics (QM/MM) modeling of this reaction, assigning Gln61 either to QM or to MM parts of a large molecular model for the Ras(GTP)-GAP complex. We show that the initial Ras(GTP)-GAP-H2O and final Ras(GDP)-GAP-Pi structures, where GDP and Pi denote guanosine diphosphate and inorganic phosphate, are described similarly in the QM(Gln)/MM and QM/MM(Gln) approaches. The first elementary step of the reaction, i.e., a low-energy cleavage of the O3B-PG bond in GTP, is also characterized alike in both variants. However, formation of the inorganic phosphate Pi is described differently depending on the approach. If the Gln61 side chain is allowed to participate in the proton shuttle, as modeled in the QM(Gln)/MM variant, the computed reaction pathway shows the rate-determining energy barrier of 15 kcal/mol, in agreement with the observed kinetics. This glutamine-assisted mechanism is also consistent with the known experimental results of structural, mutational and spectroscopy studies. If Gln61 is excluded from the QM part, as in the QM/MM(Gln) variant, the reaction pathway follows the substrate-assisted mechanism with an unrealistic activation barrier of 25 kcal/mol. Therefore, we demonstrate here the preference of the glutamine-assisted mechanism in GTP hydrolysis, in which the conserved glutamine plays a decisive role, switching between the amide and imide tautomer forms. This work is supported by the Russian Science Foundations (project # 14-13-00124).