title: Model reduction for stochastic CaMKII reaction kinetics in synapses by graph-constrained correlation dynamics.
abstract: A stochastic reaction network model of Ca(2+) dynamics in synapses (Pepke et al PLoS Comput. Biol. 6 e1000675) is expressed and simulated using rule-based reaction modeling notation in dynamical grammars and in MCell. The model tracks the response of calmodulin and CaMKII to calcium influx in synapses. Data from numerically intensive simulations is used to train a reduced model that, out of sample, correctly predicts the evolution of interaction parameters characterizing the instantaneous probability distribution over molecular states in the much larger fine-scale models. The novel model reduction method, 'graph-constrained correlation dynamics', requires a graph of plausible state variables and interactions as input. It parametrically optimizes a set of constant coefficients appearing in differential equations governing the time-varying interaction parameters that determine all correlations between variables in the reduced model at any time slice.
authors.affiliation: Department of Computer Science, University of California Irvine CA 92697, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Johnson
authors.forename: Tom
authors.initials: T
authors.lastname: Bartol
authors.forename: Terrence
authors.initials: T
authors.lastname: Sejnowski
authors.forename: Eric
authors.initials: E
authors.lastname: Mjolsness
mesh_terms: D000465:Algorithms; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000737:chemistry* / Q000378:metabolism; D002147:Calmodulin / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D008959:Models, Neurological; D056004:Molecular Dynamics Simulation; D011336:Probability; D013569:Synapses / Q000201:enzymology*
chemical_list: D002147:Calmodulin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium