Paper Citing NAMD - Abstract
Jena, Bhanu P.
Understanding Membrane Fusion: Combining Experimental and Simulation Studies
METHODS IN NANO CELL BIOLOGY, 90:183-+, 2008
Target membrane proteins, SNAP-25 and syntaxin (t-SNARE), and secretory vesicle-associated membrane protein (v-SNARE), are part of the conserved protein complex involved in fusion of opposing bilayers in biological systems in the presence of calcium. It is known that SNARE interaction allows opposing bilayers to come close within a distance of similar to 2.8 angstrom, enabling calcium to drive membrane fusion. X-ray diffraction studies and light scattering measurements performed in SNARE-reconstituted liposomes demonstrate that when reconstituted t-SNARE-and v-SNARE-vesicles are allowed to interact prior to calcium addition, membrane fusion fail to occur. These results suggest that hydrated calcium ions are too large (similar to 6 angstrom) to fit between the SNARE-apposed bilayer space, and as a result, unable to induce membrane fusion. In the presence of calcium, however, t-SNARE vesicles interact with v-SNARE vesicles, allowing formation of calcium-phosphate bridges between the opposing bilayers, resulting in the expulsion of coordinated water at the phosphate of the phospholipid head-groups, and due to disruption of the water shell around the calcium ion, enabling lipid mixing and membrane fusion. This hypothesis when tested using atomistic molecular dynamic simulations in the isobaric-isothermal ensemble using hydrated dimethylphosphate anions (DMP(-)) and calcium cations, demonstrate formation of DMP-Ca(2+) complexes and the consequent removal of water, supporting the hypothesis. As a result of Ca(2+)-DMP self-assembly, the distance between anionic oxygens between the two DMP molecules is reduced to 2.92 angstrom, which is in agreement with the 2.8 angstrom SNARE-induced apposition established between opposing lipid bilayers, reported from X-ray diffraction measurements.
