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.

Spin effects govern DNA/RNA nucleotide polymerization

“…This is the time-consuming process that spans in general over the millicecond interval (this interval is beyond the accepted computational interval and might be thought as an imaginary asymptotic limit). The same is valid for the PP i formation of the two 3 fragments and complete magnesium oxidation accompanied by producing the stable Mg 2+ (H 2 O) 6 complex (see above) [44,45] that is able to act anew as a catalyst in ATP cleavage [16].…”

“…This is, specifically, observed in approaching the water molecules to the Mg (structure-2), Figure 3(b), Table 1, and adding new water molecules from the water reservoir (not shown), see section II, that favors restoring the most stable in water Mg(H 2 O) 6 configuration [16]. The restoring of the Mg(H 2 O) 6 is not directly coupled with the electron pumping onto the O and the proton transfer on it from the Zundel cation, Figures 3(a), (b).…”

“…The restoring of the Mg(H 2 O) 6 is not directly coupled with the electron pumping onto the O and the proton transfer on it from the Zundel cation, Figures 3(a), (b). The processes are separated in time: the first acquires milliseconds, while the latter proceeds in a picosecond-nanosecond interval [15,16]. Figure 3(a) shows that initially the spin density (green) is redistributed between the Mg and O atoms with the Mg slightly bound to the water molecules and the 3 PO  .…”

“…It is initiated by altering spin symmetry of the Mg 2+ upon its excitation from the lowest in energy S state into the lowest in energy triplet (T) state. The mechanism was recently revealed in quantum computer experiments [15,16] and indirectly proved by the Chemically Induced P nuclei [15]. The excitation into the T state that proceeds in vitro in a femtosecond interval results in producing the two ion-radicals, Mg + and NТP 3-(the dot stands for a radical), with the latter showing a rapid decomposition into the NМP -.…”

“…] SS (SS stands for a spin-separated state with one electron on the Mg and the rest on the NTP) is, on the contrary, highly rapid, 5 ps [15,16]. At this very point one must make it clear that the 5 ps interval assumes the pure decomposition time when the Mg cation is just chelated by the O2-O3 fragment of the ATP and the chelate is energetically unstable (the difference in the total energy for the separated ATP+ (water shell) molecule and the (H 2 O) 6 Mg 2+ and their chelate is around 20 kcal/mol) that allows it to show such a fast decomposition.…”