A stochastic model for virus traffic
We used a tug of war model in which the motors dynein (D) and kinesin (K) step [1-2] along a 1D microtubule, bind [3-5] to and unbind [4-6] from the cargo. The number of available binding sites on the virus is indicated with ρ. Given the parameters r and ρ, trajectories are stochastically simulated and then segmented to extract length and velocity distributions for the directed (fast) motion runs.
Model parameters identified from experimental data using Evolution Strategies
The model parameters are identified by using a Covariance Matrix Adaptation Evolutionary Strategy to minimize the distance (Kullback-Leibler Divergence) between simulated and biological length and velocity distributions.
Model predictions for virus binding sites
Given the predicted range of 6-16 binding sites and the viral capsid structure, interfaces between protein hexon and protein IX (pIX) are left as candidates to harbor the motor binding sites. We imaged pIX deficient adenoviruses and the corresponding run length and velocity distributions show that bidirectionality is preserved.
Summary of Findings
- The proposed model accurately reproduces motor activity
- Found an optimal range of 6-16 binding sites
- Virus dynamics are characterized by low number of bound motors
- Strong correlation between velocity and number of motors
- High dependence on the unbinding rates
- We predict that hexon provides the motor binding sites
People: Mattia Gazzola, Basil Bayati
Collaborators: Urs Greber, Christoph Burkhardt (University of Zurich, Institute of Zoology)
Funding:SystemsX
Publications
2009
- M. Gazzola, C. J. Burckhardt, B. Bayati, M. Engelke, U. F. Greber, and P. Koumoutsakos, “A stochastic model for microtubule motors describes the in vivo cytoplasmic transport of human adenovirus,” PLoS Comput. Biol., vol. 5, iss. 12, p. e1000623, 2009.