We computationally model the kinesin chemomechanical cycle in order to: 1) motivate and interpret our experiments, 2) test hypotheses, and 3) gain intuitive insights into mechanics at the nano scale. We have used stochastic (Monte Carlo) models of the kinesin hydrolysis cycle to understand how intermolecular tension controls processivity and interpret our single-molecule data (1,2). To understand diffusive aspects of the free head stepping to the next binding site, we have carried out Brownian Dynamics models that incorporate tethered diffusion (3). To understand the mechanics of the neck linker domain, we have carried out Molecular Dynamics simulations of neck linker pulling (4). Finally, we are working with John Fricks (PSU Statistics) to develop novel approaches to modeling the hydrolysis cycle (5,6)
1. Muthukrishnan, G., Zhang, Y., Shastry, S., and Hancock, W.O. (2009). The processivity of kinesin-2 motors suggests diminished front-head gating. Current Biology 19, 442-447. Supplemental Data.
2. Shastry, S., and Hancock, W.O. (2010). Neck linker length determines the degree of processivity in Kinesin-1 and Kinesin-2 motors. Current Biology 20, 939-943. Supplemental Data.
3. Kutys, M.L., Fricks, J., and Hancock, W.O. (2010). Monte Carlo analysis of neck linker extension in kinesin molecular motors. PLoS Computational Biology 6, e1000980.
4. Hariharan, V., and Hancock, W.O. (2009). Insights into the mechanical properties of the kinesin neck linker domain from sequence analysis and molecular dynamics simulations. Cellular and Molecular Bioengineering 2, 177-189.
5. Hughes, J., Hancock, W.O., and Fricks, J. (2011). A matrix computational approach to kinesin neck linker extension. Journal of Theoretical Biology 269, 181-194.
6. Hughes, J., Hancock, W.O., and Fricks, J. (2011). Kinesins with Extended Neck Linkers: A Chemomechanical Model for Variable-Length Stepping. Bull Math Biol (In Press).
Other Research Topics: