Magnesium cation initiates nucleoside triphosphate to monophosphate conversion by a radical mechanism: Quantum molecular dynamics simulation

Abstract

A DFT:B3LYP (6-311G** basis set) quantum molecular dynamics simulation was used to study the mechanism of Mg2+-induced conversion of guanosine triphosphate (GTP) to guanosine monophosphate (GMP). The computations were performed at 310 K in a bath of 178 water molecules surrounding the Mg(H2O)2-GTP complex and mimicking the hydration shells. Dissociation of the Mg2+-GTP complex (process duration, 5 ps) produces two phosphate anions (Pi), a hydrated Mg2+ cation, atomic oxygen, and a highly reactive GMP radical. This radical appears as a result of the action of Mg2+, which initiates the radical mechanism of GTP cleavage. At the initial stage of the interaction with GTP, Mg2+ is reduced to Mg+, producing an ion-radical pair +Mg·-·GTP3−. In the absence of Mg2+, an inert GMP molecule forms instead of the GMP radical as a result of hydrolytic cleavage of GTP via an ionic mechanism. Presumably, formation of the GMP radical and analogous radicals with adenosine, cytidine, thymidine, and uridine is a key point in the syntheses of deoxyribonucleic and ribonucleic acids.