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Kinesin's Biased Stepping Mechanism: Amplification of Neck Linker Zippering

School of Physics and Center for Nonlinear Science, Georgia Institute of Technology, Atlanta, Georgia

Correspondence: Address reprint requests to R. F. Fox, Tel.: 404-894-5260; E-mail: ron.fox{at}physics.gatech.edu.

A physically motivated model of kinesin's motor function is developed within the framework of rectified Brownian motion. The model explains how the amplification of neck linker zippering arises naturally through well-known formulae for overdamped dynamics, thereby providing a means to understand how weakly-favorable zippering leads to strongly favorable plus-directed binding of a free kinesin head to microtubule. Additional aspects of kinesin's motion, such as head coordination and rate-limiting steps, are directly related to the force-dependent inhibition of ATP binding to a microtubule bound head. The model of rectified Brownian motion is presented as an alternative to power stroke models and provides an alternative interpretation for the significance of ATP hydrolysis in the kinesin stepping cycle.