Wilson, Richard John (2011) Simulating the kinesin walk : towards a definitive theory. PhD thesis, University of Warwick.

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Abstract

Dementia is a set of incurable, fatal diseases characterised by irreversible degeneration of the brain. One theory of its cause is the failure of intracellular transport in the axons of the neurons that compose the brain. Kinesin is a key motor transporting vital cargo along the axon. We know that this motor is a bipedal engine stepping forward along a polypeptide track but it is too small and fast for this motion to be observed using current experimental techniques. The stepping detail is therefore open to debate. This study firstly addresses the question of how kinesin steps and secondly pilots a possible method for investigating transport disruption in silico. To investigate the detail of stepping, a program has been designed and built to simulate kinesin traversing its track along a section of axon. The motor is modelled as simple, interacting agents obeying rules abstracted from known chemical and binding properties of its components. The agent-based method has proven useful and efficient on the small scale and has potential for simulating the larger and more complex system of axonal transport. This would enable investigation of transport failure in the context of finding a cure for dementia. A new model of kinesin stepping has been formulated as a consequence of performing virtual experiments using the simulation. Analysis of in vivo and in vitro experimental studies shows that the model accounts for a wide range of published results, explaining many findings. New experiments are suggested to test the model based on its falsifiable predictions. The principal conclusion of this study is that kinesin stepping is rectified Brownian motion.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QP Physiology R Medicine > RC Internal medicine
Library of Congress Subject Headings (LCSH):	Dementia -- Etiology, Kinesin -- Computer simulation
Date:	October 2011
Institution:	University of Warwick
Theses Department:	Molecular Organisation and Assembly in Cells
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Feng, Jianfeng
Sponsors:	Engineering and Physical Sciences Research Council (EPSRC)
Extent:	xvi, 154, [28] p. : ill., charts
Language:	eng
URI:	http://wrap.warwick.ac.uk/id/eprint/49216

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