title: State-dependent doubly weighted stochastic simulation algorithm for automatic characterization of stochastic biochemical rare events.
abstract: In recent years there has been substantial growth in the development of algorithms for characterizing rare events in stochastic biochemical systems. Two such algorithms, the state-dependent weighted stochastic simulation algorithm (swSSA) and the doubly weighted SSA (dwSSA) are extensions of the weighted SSA (wSSA) by H. Kuwahara and I. Mura [J. Chem. Phys. 129, 165101 (2008)]. The swSSA substantially reduces estimator variance by implementing system state-dependent importance sampling (IS) parameters, but lacks an automatic parameter identification strategy. In contrast, the dwSSA provides for the automatic determination of state-independent IS parameters, thus it is inefficient for systems whose states vary widely in time. We present a novel modification of the dwSSA--the state-dependent doubly weighted SSA (sdwSSA)--that combines the strengths of the swSSA and the dwSSA without inheriting their weaknesses. The sdwSSA automatically computes state-dependent IS parameters via the multilevel cross-entropy method. We apply the method to three examples: a reversible isomerization process, a yeast polarization model, and a lac operon model. Our results demonstrate that the sdwSSA offers substantial improvements over previous methods in terms of both accuracy and efficiency.
authors.affiliation: Department of Computer Science, University of California Santa Barbara, Santa Barbara, California 93106, USA. min@cs.ucsb.edu
authors.forename: Min K
authors.initials: MK
authors.lastname: Roh
authors.forename: Bernie J
authors.initials: BJ
authors.lastname: Daigle
authors.forename: Dan T
authors.initials: DT
authors.lastname: Gillespie
authors.forename: Linda R
authors.initials: LR
authors.lastname: Petzold
mesh_terms: D000465:Algorithms; D001669:Biochemical Phenomena; D019204:GTP-Binding Proteins / Q000737:chemistry; D007536:Isomerism; D007763:Lac Operon; D056004:Molecular Dynamics Simulation; D011336:Probability; D013269:Stochastic Processes; D013816:Thermodynamics
chemical_list: D019204:GTP-Binding Proteins