Efficient stochastic simulation of chemical kinetics networks using a weighted ensemble of trajectories

We apply the weighted ensemble (WE) simulation strategy, previously employed in the context of molecular dynamics simulations, to a series of systems-biology models that range in complexity from a one-dimensional system to a system with 354 species and 3680 reactions. WE is relatively easy to implement, does not require extensive hand-tuning of parameters, does not depend on the details of the simulation algorithm, and can facilitate the simulation of extremely rare events. For the coupled stochastic reaction systems we study, WE is able to produce accurate and efficient approximations of the joint probability distribution for all chemical species for all time t. WE is also able to efficiently extract mean first passage times for the systems, via the construction of a steady-state condition with feedback. In all cases studied here, WE results agree with independent brute-force calculations, but significantly enhance the precision with which rare or slow processes can be characterized. Speedups over brute-force in sampling rare events via the Gillespie direct Stochastic Simulation Algorithm range from similar to 10(12) to similar to 10(18) for characterizing rare states in a distribution, and similar to 10(2) to similar to 10(4) for finding mean first passage times. (C) 2013 AIP Publishing LLC.