Applied Analysis Seminar

Extracting Effective Dimerization / Dissociation Constants From a Spatial Stochastic Simulation - Talk #2

Date: 4/4/2018
Time: 3:30PM-4:30PM
Place: 315 Armstrong Hall

Christopher T. Short & Ádám M. Halász*

Abstract: Dynamical models are necessary for understanding how biological functionality emerges from a complex network of molecular interactions, such as in cell signaling. Because of their complexity (large size, nonlinear dynamics, resulting in many possible behaviors) the predictive power of dynamical models depends crucially on the precise values of the relevant parameters. Unfortunately, another consequence of complexity and a feature of living systems is that such dynamical parameters cannot be measured in isolation, the way physical parameters are.

Experimental techniques that provide molecular level resolution, such as single particle tracking (SPT), open the possibility of extracting dynamical parameters directly from experimental data, obtained in vivo, from the same system. However, this is a window into much more detailed picture than the “mesoscopic” dynamical parameters required for signaling networks. To bridge the resolution gap, we may turn to detailed simulations that emulate the movement of individual molecules. These models can extend to the experimental setup and be validated against the microscopic data; we can then extract relevant (effective or “coarse-grained”) dynamical parameters from the spatial simulation.

Here we focus on issues that emerge from a baseline comparison between spatial and non-spatial simulations of a simple reversible dimerization process; the spatial simulation employed an algorithm similar to Smoldyn (first-principles Brownian motion and collision triggered dimerization / dissociation triggered by Poisson processes). We focus on two aspects that need to be addressed when considering a non-spatial correspondent for a spatial model: (1) dimer and monomer lifetimes in the presence of geminate recombination (2) the time course of dimerization / dissociation. Our tentative conclusion is that, under certain circumstances, geminate recombination is a true physical process, and as a result, the spatial process of dimerization / dissociation cannot be represented by a simple mass-action rate law.

*Work in collaboration with Jeremy Edwards (U. of New Mexico) and Romica Kerketta (UNM / Medical College of Wisconsin).

All are welcome.