monte carlo analysis of neck linker extension in kinesin molecular motors蒙特卡罗分析颈部链接器扩展的驱动蛋白分子马达.pdfVIP

Monte Carlo Analysis of Neck Linker Extension in Kinesin Molecular Motors 1 2 1 Matthew L. Kutys , John Fricks *, William O. Hancock * 1 Department of Bioengineering, The Pennsylvania State University, University Park, Pennsylvania, United States of America, 2 Department of Statistics, The Pennsylvania State University, University Park, Pennsylvania, United States of America Abstract Kinesin stepping is thought to involve both concerted conformational changes and diffusive movement, but the relative roles played by these two processes are not clear. The neck linker docking model is widely accepted in the field, but the remainder of the step – diffusion of the tethered head to the next binding site – is often assumed to occur rapidly with little mechanical resistance. Here, we investigate the effect of tethering by the neck linker on the diffusive movement of the kinesin head, and focus on the predicted behavior of motors with naturally or artificially extended neck linker domains. The kinesin chemomechanical cycle was modeled using a discrete-state Markov chain to describe chemical transitions. Brownian dynamics were used to model the tethered diffusion of the free head, incorporating resistive forces from the neck linker and a position-dependent microtubule binding rate. The Brownian dynamics and chemomechanical cycle were coupled to model processive runs consisting of many 8 nm steps. Three mechanical models of the neck linker were investigated: Constant Stiffness (a simple spring), Increasing Stiffness (analogous to a Worm-Like Chain), and Reflecting (negligible stiffness up to a limiting contour length). Motor velocities and run lengths from simulated paths were compared to experimental results from Kinesin-1 and a mutant conta