The role of magnesium in hydrolysis of triphosphates in water: Quantum mechanical/molecular mechanical modeling

The mechanism of hydrolysis of deprotonated methyl triphosphate (MTP) to methyl diphosphate (MDP) and inorganic phosphate (Pi) in water clusters in the presence and absence of magnesium cations has been modeled. Modeling has been performed by the effective fragment potential-based quantum mechanical/molecular mechanical method. The energies and energy derivatives in the quantum subsystem including MTP, reacting water molecules, and Mg2+ has been calculated at the density functional theory (B3LYP) level, whereas water-water interactions have been described by the TIP3P model potential. The minimum-energy path for the reaction MTP + H2O → MDP + Pi is consistent with a two-stage dissociative process in the absence of Mg2+ and with a one-stage mechanism in the presence of Mg2+.