Molecular Simulation Study on the Walking Mechanism of Kinesin Dimers on Microtubules

Molecular Simulation Study on the Walking Mechanism of Kinesin Dimers on Microtubules

Kinesins are motor proteins that, when they hydrolyze ATP, travel unidirectionally along microtubules. While the general characteristics of the kinesin walking system are becoming increasingly apparent, there are still some key questions unanswered, such as how ATP’s chemical energy is transformed into mechanical energy and processed. In this research, we found through molecular simulations and free energy calculations that kinesin favors an extended shape with its unfolded microtubule-binding interface (MTBI) motif in aqueous solution, as seen in a recent kinesin-8 x-ray structure. We derived atomic structures from the kinesin dimer-microtubule complexes in both two-head-bound and one-head bound states via the versatile fitting of two newly published cryo-electron microscopy (cryo-EM) maps. Free energy calculations have shown that microtubule-bound kinesin has lower free energy than the extended form and that the difference in free energy is within the range of free energy produced by ATP hydrolysis. A completely new mechanism by which kinesin dimers walk on microtubules is indicated by the transition between the extended and compact shapes, the structural differences of the leading and trailing heads and atomic force simulations. To identify kinesin dimers walking on microtubules, a structure cycle and energy cycle are provided. A new goal for the control of kinesin is to classify the extended form of kinesin.

Author (s) Details

Alicia Pan
Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Allen Pan
Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Dr. Bernard R. Brooks
Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Dr.  Xiongwu Wu
Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.

View Book :- https://stm.bookpi.org/CACB-V1/issue/view/12

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