(A) Receptor combination approach: predicted avidities of an htBVL binding to cells expressing one or two complementary receptors, and the number of possible combinations for potential targeting. High avidity and specificity can be expected for heterobivalent binding. (B) GPCR modeling. The two receptors can pack in any number of orientations, and the distance span between the two binding pockets could be up to 100 Å long depending on the dimer packing, domain swapping, or lipid rafts involvement (also see refs 3, 14, 18, 22, and 23).