Force generation with negative intramolecular cooperativity. The orange shading indicates active molecules. In any one molecule, only one of the two heads is involved in force generation, whereas the other head is redundant for the duration of the force-generating event. In subsequent cycles, the heads might re-assort and the redundant head might be active instead. For each active head, the cycle of force generation begins with ADP release, which converts the head to stable strong binding, and continues with ATP binding and Pi release, which returns the head to a weak binding Eg5•ADP state. Weakly bound Eg5•ADP heads (left column) remain attached to the MT in a low-friction state that can be readily slid along the MT by forces developed by other, active molecules in the array. D, ADP; MT, microtubule.