Molecular dynamics DFT:B3LYP study of guanosinetriphosphate conversion into guanosinemonophosphate upon Mg2+ chelation of ? and ? 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 Mg(2+) (magnesium cofactor). The computations are carried out at 310 K in a volume of 178 water molecules, which surround the Mg(2+)-GTP complex and imitate the effect of solution. Over 5 ps, Mg(2+)-GTP appears to be fully decomposed, yielding five final products: two hydrated molecules of inorganic phosphate Pi, a hydrated Mg(2+), 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 Mg(2+), which initiates a radical mechanism of GTP cleavage. At the initial stage, Mg(2+) undergoes reduction to Mg(+), accompanied by the formation of an ion-radical pair with GTP, (+)Mg*-*GTP(3-). Without Mg(2+), 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.