(185y) Divalent Cations-Dimethylphosphate Complex Formation: Providing Insights into Membrane Fusion In Cells
- Conference: AIChE Annual Meeting
- Year: 2008
- Proceeding: 2008 Annual Meeting
- Group: Computational Molecular Science and Engineering Forum
- Time: Monday, November 17, 2008 - 6:00pm-8:30pm
Prior x-ray diffraction, light scattering, photon correlation spectroscopy, and atomic force microscopy experiments suggest that SNARE-induced membrane fusion in cells proceeds as a result of calcium bridging opposing bilayers, which leads to the release of water from hydrated Ca2+ ions as well as the loosely coordinated water at PO-lipid head groups . It is hypothesized that the combined effect of local dehydration of phosphate head groups, as a result of Ca2+ bridging, leads to a destabilization of lipid bilayers and resulting membrane fusion. This hypothesis was tested in the current study by performing atomistic molecular dynamic simulations in the isobaric-isothermal ensemble on dimethylphosphate anions (DMP-) and Ca2+ in water at 298 K and 1.01 bar. Examination of molecular configurations obtained from the molecular dynamics simulations reveals the establishment of self-assembled Ca2+ - DMP- complexes. Calcium ions can bridge two opposing DMP- molecules, resulting in the formation of a somewhat ring-like structure .
Experimental evidence shows that other divalent cations, such as magnesium and barium, may also initiate fusion, but at slower rate [3,4]. In this study, molecular dynamics simulations were preformed to test if other divalent cations self assemble with DMP- under same molecular dynamics conditions. Simulations show significantly fewer incidents of DMP-Mg-DMP bridges forming. Simulations of Ba2+ show no incidents of bridging dimethylphosphate oxygens. Radial distribution functions and number integrals show the depletion of water around DMP- head groups and hydrated divalent cations upon bridging incidents.
Ab initio calculations were preformed to study the stability of DMP- and its complexes with divalent cations in the presence of implicit solvent. Calculations were preformed at the B3LYP/6-31G(d,p) level of theory and CPCM solvent model. The data indicate that calcium posses a higher binding affinity to DMP- than Mg2+ or Ba2+. Furthermore, calcium favors participating in ring complexes over forming a single bridge between two DMP- molecules.
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