Effect of Magnesium on Calcium and Oxalate Ion Binding.
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Introduction: Magnesium (Mg2+) has been shown to be a kidney stone inhibitor however the exact mechanism of its effect is unknown. Using theoretical models, the interaction of calcium and oxalate were examined in the presence of Mg2+. Methods: Molecular dynamic simulations were performed with NAMD and CHARMM27 force field. The interaction between calcium (Ca2+) and oxalate (Ox2-) ions were examined with and without magnesium. Concentrations of calcium and oxalate were 0.15 M and placed in electroneutral cubic box of length 48 Angstrom. Magnesium (Mg2+) was then placed into the box at physiologic concentrations and the interaction between calcium and oxalate was observed. In addition, the effect of uric acid, citrate and pH were examined in regards to the effect of Mg2+ inhibition. Each system was allowed to run until a stable crystalline structure was formed. Results: In the presence of Mg2+, the oxalate binding pair is disrupted and shortens the contact between Ca and oxalate. This reduction is between 100 and 1000 times shorter then without Mg2+ present. The density of Mg2+ increases this effect. The effect was only observed when 2 Mg2+ were bound to oxalate. With the addition of uric acid, calcium and oxalate will precipitate. Mg2+ inhibition is synergistic with citrate and continues to inhibit crystallization with acidic pH levels. Conclusion: Calcium and oxalate ions in the presence of magnesium have a shortened contact time. The effect of Mg2+ is appears to be effected by density and binding position. Mg2+ inhibitory effect is negated by uric acid, synergistic with citrate and remains effective in acidic environments. Further studies are needed to see if this can be applied to in vivo models as well as extending this to other stone inhibitors and promoters.