Computational modeling of kinesin stepping.
Kinesin is a walking motor protein that shuttles cellular cargoes along microtubules (MTs). This protein is considered as an information processor capable of sensing cellular inputs and transforming them into mechanical steps. Here, we propose a computational model to describe the mechanochemical kinetics underlying forward and backward stepping behavior of kinesin motor as a digital circuit designed based on an adenosine triphosphate (ATP)-driven finite state machine. Kinetic analysis suggests that the backward stepping of kinesin is mainly driven by ATP hydrolysis, whereas ATP synthesis rises the duration of this stepping. It is shown that kinesin pausing due to waiting for ATP binding at limiting ATP concentration ([ATP]) and low backward loads could be longer than that caused by low rate of ATP synthesis under high backward loads. These findings indicate that the pausing duration of kinesin in MT-bound (M·K) kinetic state is affected by [ATP], which in turn affects its velocity at fixed loads. We show that the proposed computational model accurately simulates the forward and backward stepping behavior of kinesin motor under different [ATP] and loads.
School of Information and Communication Technology, Gold Coast Campus, Griffith University , Gold Coast, Queensland 4222, Australia.
Hamidreza
H
Khataee
Alan Wee-Chung
AW
Liew
D000255:Adenosine Triphosphate / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D007700:Kinetics; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D013269:Stochastic Processes
D000255:Adenosine Triphosphate; D016547:Kinesins