The simulations we proposed will help elucidate the mechanism, energetics and kinetics of the action of ion-complexing molecules, or ionophors, at a phospholipid bilayer. Our efforts will be complimented by synthesis of these model ionophores in Leo Paquette's research group at Ohio State and measurement of transport characteristics in collaboration with Frank G. Ridell at University of St. Andrews. We propose to calculate a free energy surface at various levels of approximation, the most approximation being also the most feasible. Free energetics of ion association with an ionosphore in aqueous solvent with no modeling of a phospholipid bilayer. This should give us information about solvent displacement as the ion approaches the ionophore, but does not describe the inhomogeneous membrane environment. Crudely model the membrane/solvent interface as that between two immiscible fluids. This still lacks many important features, but at last the inhomogeneity of the membrane in terface is there. Happily, there are experimental measurements of ionophore-mediated transport between two aqueous regions across an immiscible non-polar layer to which this situation corresponds. Realistic all-atom simulations of an ionophore within a bilayer. We expect to complete the first and part of the second level of description with the resources requested in this proposal. We will study the feasibility of all-atom calculations.
Showing the most recent 10 out of 292 publications
