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

John Hughes, William O. Hancock, John Fricks

Research output: Contribution to journalArticle

10 Citations (Scopus)

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

Fingerprint

Kinesin
kinesin
neck
Neck
Microtubules
matrix
Myosin
Worm
Computer Experiments
Binding sites
Stochastic models
Myosins
myosin
microtubules
Sensitivity analysis
Uncertainty
Stochastic Model
Sensitivity Analysis
sensitivity analysis
binding sites

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology
  • Mathematics(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Pharmacology
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics

Cite this

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Kinesins with Extended Neck Linkers : A Chemomechanical Model for Variable-Length Stepping. / Hughes, John; Hancock, William O.; Fricks, John.

In: Bulletin of Mathematical Biology, Vol. 74, No. 5, 01.05.2012, p. 1066-1097.

Research output: Contribution to journalArticle

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