Figure 3.

Evaluation of DA-unbinding energy from hDAT in the IFS. Three conformers with different ion occupancy are shown: (A) DA-bound in the presence of two sodium ions and one chloride ion (IFo₃*); (B) DA-bound in the presence of one Na⁺ ion, after the release of Na2 and one chloride (IFo₁*); and (C) DA-bound in the absence of ions (IFo₀*). (D) Comparison of the free-energy changes for the forward annihilation of DA under the three conditions: as a free molecule in the aqueous environment (gray line with open circles), bound to IFo₃* (blue line with diamonds), bound to IFo DAT in the presence of one sodium ion, IFo₁* (red line with squares) and in the absence of other ions, IFo₀* (purple line with crosses). The respective binding affinities are listed in Table 2.