Mechanistic Modeling of Cellular Systems

项目摘要 该提案旨在建立一个国家资源，用于细胞机制建模， 系统服务于细胞和系统生物学家的大型社区。该资源将 包括COPASI和虚拟单元（VCell）软件平台，这可以说是最 全面和广泛使用的生物物理计算建模工具， 控制细胞功能的机制VCell支持许多关键的生物物理机制， 包括反应动力学、扩散、流动、膜运输、横向膜扩散 电生理学和基于规则的多状态/多分子相互作用模型。模拟 可以基于0 D、1D、2D或3D分析或实验图像几何形状。用户 可以在多种可用的模拟方法中选择：常微分方程， 偏微分方程，随机反应动力学，无网络模拟，空间 基于粒子的模拟和空间混合随机/确定性模拟。COPASI 能够模拟和分析复杂的生化反应网络， 确定性或随机性。它提供了广泛的分析工具，包括参数 估计/优化，稳态分析，化学计量分析，灵敏度分析和 代谢控制分析VCell和COPASI各自拥有数千名活跃用户。 总的来说，他们的用户每年依靠这些软件系统产生超过100篇论文。两 VCell和COPASI将在康涅狄格大学医学院举办。因此 资源将受益于：（1）它将在其下运作的共同体制组织; (2)一个联合网站;（3）一个共同的高性能计算设施，将服务于 用户的计算密集型需求;（4）协调对用户的培训和推广 社区的形式，基于网络的文档和教程，每年计算细胞 生物学讲习班和许多路演在国家和国际会议。 此外，外部系统生物学软件将利用VCell和COPASI 开发人员作为用户友好的平台，广泛传播他们的第三方算法， 软件和数据库。最后，资源将积极参与软件标准 社区，以确保软件和模型的可重复性和可重用性， 生成.

Project Summary This proposal aims to establish a National Resource for Mechanistic Modeling of Cellular Systems to serve the large community of cell and systems biologists. The Resource will encompass COPASI and Virtual Cell (VCell) software platforms, which are arguably the most comprehensive and widely used tools for computational modeling of the biophysical mechanisms controlling cell function. VCell supports a number of key biophysical mechanisms, including reaction kinetics, diffusion, flow, membrane transport, lateral membrane diffusion, electrophysiology and rule-based models of multi-state/multimolecular interactions. Simulations can be based on 0D, 1D, 2D or 3D analytical or experimental image-based geometries. Users may choose among multiple available simulation approaches: ordinary differential equations, partial differential equations, stochastic reaction kinetics, network-free simulations, spatial particle-based simulations and spatial hybrid stochastic/deterministic simulations. COPASI enables the simulation and analysis of complex biochemical reaction networks either deterministically or stochastically. It offers a broad range of analysis tools including parameter estimation/optimization, steady state analysis, stoichiometric analysis, sensitivity analysis and metabolic control analysis. VCell and COPASI each boast thousands of active users. Collectively, their users produce >100 papers per year relying on these software systems. Both VCell and COPASI will be hosted at the University of Connecticut School of Medicine. Thus, the Resource will benefit from: (1) the common institutional organization under which it will operate; (2) a joint website; (3) a common high performance computing facility that will serve the computationally intensive needs of users; (4) coordinated training and outreach to the user community in the form of web-based documentation and tutorials, a yearly Computational Cell Biology Workshop and numerous roadshows at national and international meetings. Additionally, VCell and COPASI will be leveraged by external systems biology software developers as user-friendly platforms for the wide dissemination of their third party algorithms, software and databases. Finally, the Resource will actively engage with the software standards community to assure the reproducibility and reusability of both the software and the models it generates.