Modeling and simulation of biochemical networks has become an essential activity to aid in the understanding of cellular behavior and to facilitate quantitative interpretation of modern experiments. A new approach, "systems biology", is being advocated which combines modeling, simulation and quantitative experiments. The novelty of systems biology is that experiments, mathematical modeling, and computer simulation are practiced in a cooperative way, the results of one being used for subsequent iterations of the others. Arguably, to fulfill the promise of systems biology there is a need for software tools to be able to appropriately connect models to experiments. We propose to address this, and other systems biology needs, with continuing development of our software COPASI, which is the successor of the widely used Gepasi. This project will also provide support to the vibrant community of COPASI users/biomedical researchers. We will address this with the following Specific Aims: Aim 1: Enable COPASI with new functionality to provide advanced model analyses. This will include adding algorithms for nonlinear dynamical analysis, model complexity reduction, improved parameter estimation and methods for closing the loop of experiment-model-experiment, and parallelization of certain algorithms. Aim 2. Improve and extend interoperability and standards compliance. COPASI will be equipped to facilitate users to create and maintain models according to the MIRIAM standard, and with methods to act as a client and provider in the SBW environment. SBML support will continue and be enhanced. Aim 3. Software maintenance. A testing plan will be established, including appropriate testing suites and procedures;bug reports will be collected and fixed;suggestions for improvement will be collected from users and followed. Aim 4. Support the modeling community. Providing online support tools, such as a user forum, FAQ and Wiki. An Annual COPASI User's Workshop will be held.