title: Efficient modeling, simulation and coarse-graining of biological complexity with NFsim.
abstract: Managing the overwhelming numbers of molecular states and interactions is a fundamental obstacle to building predictive models of biological systems. Here we introduce the Network-Free Stochastic Simulator (NFsim), a general-purpose modeling platform that overcomes the combinatorial nature of molecular interactions. Unlike standard simulators that represent molecular species as variables in equations, NFsim uses a biologically intuitive representation: objects with binding and modification sites acted on by reaction rules. During simulations, rules operate directly on molecular objects to produce exact stochastic results with performance that scales independently of the reaction network size. Reaction rates can be defined as arbitrary functions of molecular states to provide powerful coarse-graining capabilities, for example to merge Boolean and kinetic representations of biological networks. NFsim enables researchers to simulate many biological systems that were previously inaccessible to general-purpose software, as we illustrate with models of immune system signaling, microbial signaling, cytoskeletal assembly and oscillating gene expression.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sneddon
authors.forename: James R
authors.initials: JR
authors.lastname: Faeder
authors.forename: Thierry
authors.initials: T
authors.lastname: Emonet
mesh_terms: D001671:Biochemistry / Q000379:methods*; D003198:Computer Simulation; D007700:Kinetics; D008954:Models, Biological; D010766:Phosphorylation; D012985:Software Design; D013269:Stochastic Processes