Kinesins with extended neck linkers: a chemomechanical model for variable-length stepping

Bull Math Biol. 2012 May;74(5):1066-97. doi: 10.1007/s11538-011-9697-6. Epub 2011 Oct 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Computer Simulation
  • Kinesins / chemistry*
  • Markov Chains
  • Mechanical Phenomena
  • Models, Chemical*
  • Monte Carlo Method
  • Protein Engineering

Substances

  • Kinesins