Effect of cation concentration on molecular dynamics simulations of UDP-glucose

Glycosyl esters of nucleoside di or mono-phosphates, generally referred to as "sugar nucleotides", serve as a sugar donors during the biosynthesis of oligo- and polysaccharides; they are therefore of a primary importance in c arbohydrate metabolism in the living world. Molecular dynamics simulations were used to explore the conformational flexibility of one nucleotide sugar , UDP-glucose (UDP-Glc). The AMBER program package was used with some new p arameters especially developed for nucleotide sugars. Several simulations o n this molecule in aqueous solution, each of 2ns duration, were carried out for increasing concentrations of monovalent K+ and divalent Mg2+ ions. For the monovalent ion, it is revealed that its presence and concentration is crucial for the conformational behavior, resulting in the stabilization of the extended conformation. The preferred location of Kf is in close proximi ty to the negatively charged phosphate oxygens, but the ion moves freely an d can occupy other sites. Since the size of this cation is close that of th e water molecules, the hydration scheme is not perturbed. Completely differ ent results are obtained when the divalent Mg2+ cation is introduced in the simulation. A very strong interaction is established between the phosphate group and the cation; as a result the UDP-Glc molecule is locked in a rigi d extended geometry. The analyses of the trajectories provide new insight o n the role of the metal ion in the catalytic mechanism of glycosyltransfera ses.