fig3

Figure 3. Scheme showing the types of interactions in the two-step process of allocrite binding from the aqueous phase to ABCB1 within the membrane. Step I: Partitioning of an amphiphilic allocrite (with polar part in blue and hydrophobic part in yellow) into the extracellular membrane leaflet depends on the lateral packing density of the membrane, π_m. Moreover, partitioning into the cytosolic leaflet depends in addition on the surface potential Ψ_m of the membrane^[59]. Step II: Dipolar interactions between allocrite and transporter (including hydrogen bonding, π-π stacking, and π-cation interactions, given in the order of assumed relevance) are suggested to drive recognition, binding, and “transport” of the polar part to the middle of the membrane. Thereby it is assumed that the hydrophobic part remains in contact with the lipid environment.