NAME	Brief Description
BIONETGEN	Automatic generation of physicochemical models of biological systems with combinatorial complexity such as cellular signaling from user-specified rules for biomolecular interactions at the protein domain level, integrated with tools for reaction network simulation and analysis (53). http://cellsignaling.lanl.gov/bionetgen/
BIO-SPICE	Open source software for intra and inter-cellular modeling and simulation of spatio-temporal processes, pathways and interaction-network tools for data analysis (MIAMESpice), model composition and visualization (BioSenS, Charon, JDesigner, Sal), mathematical tools including ordinary and partial differential and stochastic equation-based methods and algorithms for the simulation of reaction and diffusion-reaction networks (BioNetS Simpathica) (54, 55). https://biospice.org/index.php
CELLDESIGNER	Gene regulatory network modeling, visual representation of biochemical semantics with SBML and database support, integration with Matlab or Mathematica ODE Solvers and direct access to SBW SBML compliant simulators such as Jarnac (56, 57). http://celldesigner.org/index.html
CELLERATOR	Open source Mathematica based package for simulation and analysis of signal transduction networks in cells and multicellular tissues, automated equation generation with arrow-based reaction notation (58). http://www-aig.jpl.nasa.gov/public/mls/cellerator/
COPASI	Stochastic and deterministic simulation of network pathways, steady state and metabolic control analysis including stability analysis, elementary and mass conservation analysis, optimization and parameter estimation and SBML support (59). http://www.copasi.org/tiki-index.php
DIZZY	Stochastic and deterministic kinetic modeling of integrated large-scale genetic, metabolic, and signaling networks with domain compartmentalization, features include modular simulation framework, reusable modeling elements, complex kinetic rate laws, multi-step reaction processes, steady-state noise estimation (60). http://magnet.systemsbiology.net/software/Dizzy
E-CELL	Object-oriented software for modeling, simulation, and analysis of large scale cellular networks, multi-algorithm multi-time scale simulation method with access to Gillespie-Gibson and Langevin stochastic algorithms, Euler and higher order adaptive methods for ordinary and algebraic differential equations, parallel and distributed computing capabilities and SBML support (61, 62). http://www.e-cell.org/software/e-cell-system
GRID CELLWARE	Grid-based modeling and simulation tool for biochemical pathways, integrated environment for diverse mathematical representations, parameter estimation using swarm algorithm and optimization, user-friendly graphical display and capability for large, complex models, stochastic algorithms such as Gillespie, Gibson and tau-leaping and deterministic algorithms based on ordinary differential equation solvers (63). http://www.bii.a-star.edu.sg/research/sbg/cellware
MCELL	Monte Carlo simulator for investigating cellular physiology, model description language or MDL used to specify ligand creation, destruction, and release as well as chemical reactions involving effectors such as receptors or enzymes, ligand diffusion modeled with 3D random walks, wide variety of numerical and imaging options (64). http://www.mcell.cnl.salk.edu and www.mcell.psc.edu
MESORD	Open source C++ software for stochastic simulation of kinetic reactions and diffusion based on next subvolume method (NSM) for structured geometries in three dimensions, SBML compatible, three-dimensional OpenGL simulation viewer (65). http://mesord.sourceforge.net/
NWKSIM	Fortran 90/95 platform for large scale general kinetic reaction network simulation, Java swing graphical user interface, unique modeling features for computation of evolving multiple compartments with trafficking and signal transduction processes, stochastic algorithms include direct Gillespie, probability weighted dynamic Monte Carlo and weighted Gibson-Gillespie Bruck, binomial and multinomial tau-leaping algorithms (32, 42).
SIGTRAN	Fortran 90/95 modeling and simulation platform for large scale reaction networks, Java swing graphical user interface, dual stochastic and deterministic (ODE/DAE) simulation modes, multistate macromolecule specification and simulation using the Firth-Bray algorithm, reaction-diffusion modeling with Fricke-Wendt algorithm, molecule tagging and tracking in signal transduction networks using a fully automated graph-theoretic algorithms for determination of unambiguous set of base species, SBML file support (42).
SIMBIOLOGY	Matlab toolkit for modeling, simulating, and analyzing biochemical pathways, graphical user interface with visual pathway expression, manual or SBML file input, stochastic or deterministic solvers, parameter estimation and sensitivity analysis, ensemble runs and post-run analysis tools with plotting. http://www.mathworks.com/products/simbiology/description4.html
SMARTCELL	Object-oriented C++ platform for modeling and simulation of diffusion-reaction networks in whole-cell context with support for any cell geometry with different cell compartments and species localization, includes DNA transcription and translation, membrane diffusion and multistep reactions as well as cell growth, localization and diffusion modeling based on mesoscopic stochastic reaction algorithm (66). http://smartcell.embl.de/introduction.html
STOCHKIT	Efficient C++ stochastic simulation framework for intracellular biochemical processes, stochastic algorithms includes Gillespie SSA and explicit, implicit and trapezoidal tau-leaping methods, Kolmogorov distance and histogram distance for quantifying difference quantification in statistical distribution shapes via Matlab, extensible to new stochastic and multiscale algorithms (67). http://www.engineering.ucsb.edu/~cse/StochKit/StochKit.html
SBTOOLBOX	Matlab toolbox offering open and user extensible environment for prototyping new algorithms,and building applications for analysis and simulation of biological systems, deterministic and stochastic simulation, network identification, parameter estimation and sensitivity analysis, bifurcation analysis, SBML model import (68). http://www.sbtoolbox.org/
VIRTUAL CELL	Model creation and simulation of cell biological processes, associates biochemical and electrophysiological data for individual reactions with experimental microscopic image data describing subcellular locations, cell physiological events simulated within empirically derived geometries, reusable, updatable and accessible models, simulation data stored on the Virtual Cell database server and is easily exportable in variety of formats (69, 70). http://www.vcell.org/