title: Coarse-Grained Model of SNARE-Mediated Docking.
abstract: Synaptic transmission requires that vesicles filled with neurotransmitter molecules be docked to the plasma membrane by the SNARE protein complex. The SNARE complex applies attractive forces to overcome the long-range repulsion between the vesicle and membrane. To understand how the balance between the attractive and repulsive forces defines the equilibrium docked state we have developed a model that combines the mechanics of vesicle/membrane deformation with an apparently new coarse-grained model of the SNARE complex. The coarse-grained model of the SNARE complex is calibrated by comparison with all-atom molecular dynamics simulations as well as by force measurements in laser tweezer experiments. The model for vesicle/membrane interactions includes the forces produced by membrane deformation and hydration or electrostatic repulsion. Combining these two parts, the coarse-grained model of the SNARE complex with membrane mechanics, we study how the equilibrium docked state varies with the number of SNARE complexes. We find that a single SNARE complex is able to bring a typical synaptic vesicle to within a distance of ∼ 3 nm from the membrane. Further addition of SNARE complexes shortens this distance, but an overdocked state of >4-6 SNAREs actually increases the equilibrium distance.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, Pennsylvania.
authors.forename: Nicole
authors.initials: N
authors.lastname: Fortoul
authors.affiliation: Department of Mechanical & Aerospace Engineering, Cornell University, Ithaca, New York.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Mechanical & Aerospace Engineering, Cornell University, Ithaca, New York.
authors.forename: Chung-Yuen
authors.initials: CY
authors.lastname: Hui
authors.affiliation: Neuroscience Department, Universidad Central del Caribe, Bayamon, Puerto Rico.
authors.forename: Maria
authors.initials: M
authors.lastname: Bykhovskaia
authors.affiliation: Department of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, Pennsylvania; Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania. Electronic address: anj6@lehigh.edu.
authors.forename: Anand
authors.initials: A
authors.lastname: Jagota
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D051381:Rats; D050600:SNARE Proteins / Q000737:chemistry* / Q000378:metabolism; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism
chemical_list: D050600:SNARE Proteins