On the origin of the ionic strength control of the motility of kinesin-14

Kinesin-14 motors are a special class of the kinesin family proteins that walk toward the minus end along the microtubule. It has the reverse directionality compared to the general conventional kinesins. The motility of kinesin-14 has been found to depend on the ionic strength. That is, when the ionic strength changes, the motility of the protein changes significantly. Understanding the origin of such effect is important both as a fundamental problem and as a part of the overall understanding of intracellular transportation. Here, we explore the molecular origin behind the lowering of motility of kinesin-14 upon increase in the ionic strength. Our study combines steered molecular dynamics and umbrella sampling simulations and binding energy calculations. It is concluded that at a low ionic strength the ADP release from the trailing or back leg has a significantly lower barrier than that from the leading or front leg. However, at a higher ionic strength the barrier of ADP release becomes lower for both the trailing and leading legs, where now the barriers for both legs are similar. In this case although the ADP release for the trailing end becomes faster (which usually corresponds to higher motility) it is also faster for the leading end, and the overall motion of both heads balance each other and the motility becomes slower. The ionic strength effect and our binding free energy calculations indicated that the motility in this system is controlled by electrostatic energy. Such effects are likely to be prominent in in-vivo cellular conditions.