Kinesins with Extended Neck Linkers: A Chemomechanical Model for Variable-Length Stepping

John Hughes, William O. Hancock, John Fricks

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

We develop a stochastic model for variable-length stepping of kinesins engineered with extended neck linkers. This requires that we consider the separation in microtubule binding sites between the heads of the motor at the beginning of a step. We show that this separation is stationary and can be included in the calculation of standard experimental quantities. We also develop a corresponding matrix computational framework for conducting computer experiments. Our matrix approach is more efficient computationally than large-scale Monte Carlo simulation. This efficiency greatly eases sensitivity analysis, an important feature when there is considerable uncertainty in the physical parameters of the system. We demonstrate the application and effectiveness of our approach by showing that the worm-like chain model for the neck linker can explain recently published experimental data. While we have focused on a particular scenario for kinesins, these methods could also be applied to myosin and other processive motors.

Original languageEnglish (US)
Pages (from-to)1066-1097
Number of pages32
JournalBulletin of Mathematical Biology
Volume74
Issue number5
DOIs
StatePublished - May 1 2012

Keywords

  • Approximating Markov chain
  • Kinesin
  • Renewal process
  • Semi-Markov process

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