Fig. 4
Comparison of Na+/Na2 release pathways calculated in PIP2-enriched and PIP2-depleted membranes. Results from the transition path theory (TPT) analysis for the release of Na+/Na2 to the intracellular environment by the wild-type hDAT in PIP2-containing membrane (top) and in PIP2-depleted membrane (bottom) systems. Arrow thickness represents relative flux magnitude for each transition. The numbers above circles show corresponding macrostate numbers. A representative conformation is shown for selected macrostates, with IL2 highlighted in orange (cartoon representation) on the transparent structure of hDAT. Density representations of the residues forming intracellular gates are shown as fuzzy background gray colors and the most probable locations of these residues within the density representation are highlighted in licorice rendering and labeled for reference. Dopamine is shown in pink licorice and sodium and chloride ions in yellow and cyan spheres, respectively. Red, green, and blue boxes highlight the three major release pathways of Na+/Na2; numbers indicate the fraction of the total flux carried by each major pathway