Molecular dynamics DFT:B3LYP study of guanosinetriphosphate conversion into guanosinemonophosphate upon Mg2+ chelation of α and β phosphate oxygens of the triphosphate tail

Abstract

A molecular dynamics DFT:B3LYP (6-31G^** basis set) study is used to elucidate the mechanism of guanosinetriphosphate (GTP) conversion into guanosinemonophosphate (GMP) upon the action of Mg²⁺ (magnesium cofactor). The computations are carried out at 310 K in a volume of 178 water molecules, which surround the Mg²⁺–GTP complex and imitate the effect of solution. Over 5 ps, Mg²⁺–GTP appears to be fully decomposed, yielding five final products: two hydrated molecules of inorganic phosphate Pi, a hydrated Mg²⁺, atomic oxygen (which in the course of a couple of subsequent reactions gains two hydrogens and converts into a water molecule) and a highly active ˙GMP radical. The radical production is linked to presence of Mg²⁺, which initiates a radical mechanism of GTP cleavage. At the initial stage, Mg²⁺ undergoes reduction to Mg⁺, accompanied by the formation of an ion-radical pair with GTP, ⁺Mg˙–˙GTP³⁻. Without Mg²⁺, an inert form of GMP (the ionic mechanism of GTP hydrolytic cleavage) rather than ˙GMP is produced. ˙GMP production, which is similar to that of ˙AMP (adenosinemonophosphate), ˙CMP (cytidinemonophosphate), ˙TMP (thymidinemonophosphate) and ˙UMP (uridinemonophosphate), plays a crucial role in DNA and RNA single chain synthesis.