Simulations of the active transport of a neutral solute based on a kinase-channel-phosphatase topology

Simulations of coupled interactions involving two opposite enzymatic reactions, solute diffusions, and electrostatic interactions between membrane charges and charged solutes were conducted under a fixed kinase-channel-phosphatase (KCP) topology oriented from the outside to the inside of a porous membrane structure. Depending on the kinase and phosphatase locations, we recently demonstrated that an active transport of a phosphorylated substrate may occur via the opposite topology, that is, a PCK topology. The present analysis demonstrates that, under a KCP membrane topology, which also behaves as a specific ATP-dependent transporter, the active transport of a neutral substrate may occur. This analogous active transport appears to be dependent on the phosphatase location and on the membrane surface potentials. A broad analysis of the role played by the main parameters taken into account in the model was conducted in order to define precisely the physico-chemical conditions and the membrane topology needed for the highest active transports within the shortest time. © 2004 Wiley Periodicals, Inc. J Comput Chem 26: 201–213, 2005