Mechanistic Modeling of Cellular Systems

项目摘要 这项建议旨在建立国家细胞力学建模资源 为庞大的细胞和系统生物学家群体服务的系统。资源将 包括COPASI和虚拟单元(Vcell)软件平台，这两个平台可以说是最 用于生物物理计算建模的全面和广泛使用的工具 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、膜传输、侧膜扩散、 多态/多分子相互作用的电生理学和基于规则的模型。模拟 可以基于基于图像的0D、1D、2D或3D解析或实验几何图形。用户 可以在多种可用的模拟方法中进行选择：常微分方程式， 偏微分方程组，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 确定地或随机地。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各自都号称拥有数千名活跃用户。 总体而言，他们的用户每年依靠这些软件系统撰写100篇论文。两者都有 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)将在其下运作的共同机构组织； (2)联合网站；(3)共同的高性能计算设施，将服务于 用户计算密集型需求；(4)对用户进行协调培训和宣传 以基于Web的文档和教程的形式的社区，每年一次的计算单元 生物讲习班，并在国内和国际会议上进行多次路演。 此外，VCell和COPASI将由外部系统生物学软件利用 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，该资源将积极参与软件标准的制定 社区以确保软件及其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.