A systems-biology approach to molecular machines: Exploration of alternative transporter mechanisms
Fig 4
Dissection of a single model exhibiting enhanced selectivity into component pathways.
The full model is shown in (A) with the net probability flows scaled by the largest edge flow, while panels (B)—(D) are various continuous cycles abstracted from the full model. (B) An ion leak pathway in which the substrate and ion bind extracellularly, but only the ion is transported into the cell because the substrate unbinds on the extracellular side. (C) A (split) cotransport pathway in which the substrate and ion both are transported into the cell. (D) A second ion leak pathway, mirroring (B), in which the decoy and ion bind extracellularly, but only the ion is transported into the cell. Overall, the substrate and decoy are both driven to unbind in the outward-facing conformation, shown on the left, due to ion leak pathways. However, due to the difference in binding affinities between decoy and substrate, the substrate is more likely to rebind and be transported into the intracellular region. The full process employs the ion leaks to enhance selectivity.