Abstract
Kinesin-1 is an ATP-driven, two-headed motor protein that transports intracellular cargoes (loads) along microtubules. The movement of kinesin-1 has generally been modeled according to its correlation with ATP cleavage (forward movement), synthesis (backward movement), or unproductive cleavage (futile consumption). Based on recent experimental observations, we formulate a mechanochemical model for this movement in which the forward/backward/futile cycle can be realized through multiple biochemical pathways. Our results show that the backward motion of kinesin-1 occurs mainly through backward sliding along the microtubule and is usually also coupled with ATP hydrolysis. We also found that with a low external load, about 80% of ATP is wasted (futile consumption) by kinesin-1. Furthermore, at high ATP concentrations or under high external loads, both heads of kinesin-1 are always in the ATP- or ADP ⋅ Pi-binding state and tightly bound to the microtubule, while at low ATP concentrations and low loads, kinesin-1 is mainly in the one-head-bound state. Unless the external load is near the stall force, the motion of kinesin-1 is almost deterministic.