Modeling Biological Complexes Using Integrative Modeling Platform.
Modeling Biological Complexes Using Integrative Modeling Platform.
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DOI：
10.1007/978-1-4939-9608-7_15
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发表时间：
2019
影响因子：
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通讯作者：
Daniel J. Saltzberg;Charles H. Greenberg;Shruthi Viswanath;Ilan E. Chemmama;Ben M. Webb;R. Pellarin;Ignacia Echeverria;A. Sali
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文献类型：
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作者：
Daniel J. Saltzberg;Charles H. Greenberg;Shruthi Viswanath;Ilan E. Chemmama;Ben M. Webb;R. Pellarin;Ignacia Echeverria;A. Sali
集成结构建模提供了大分子系统的3D模型，这些模型基于来自多种类型实验、物理原理、统计推断和先前结构模型的信息。在这里，我们提供了一个动手的现实的例子，综合结构建模的四级结构的肌动蛋白，原肌球蛋白，凝溶胶蛋白组装的基础上，电子显微镜，解决方案X射线散射，和化学交联数据的复杂性，以及排除体积，序列连接，和刚性原子X射线结构的各个亚基。我们遵循一般的四个阶段的综合建模过程，包括收集输入信息，输入信息转换成系统的表示和评分函数，采样替代模型配置的评分函数的指导下，并分析结果。这种方法的计算方面是在我们的开源集成建模平台（IMP），一个全面的和可扩展的软件包集成建模（ https://integrativemodeling.org ).特别是，我们依赖于IMP的Python建模接口（PMI）模块，该模块提供了简单的大分子表示的混合和匹配，基于不同类型信息的约束，采样算法和分析，包括输入数据和输出模型的验证。最后，我们还概述了如何将整合结构和相应的实验数据存款到PDB-Dev中，PDB-Dev是新生的全球蛋白质数据库（wwPDB）资源，用于存档和传播整合结构（ https://pdb-dev.wwpdb.org ).示例应用程序为有兴趣使用IMP对其他生物分子系统进行集成建模的用户提供了一个起点。
Integrative structure modeling provides 3D models of macromolecular systems that are based on information from multiple types of experiments, physical principles, statistical inferences, and prior structural models. Here, we provide a hands-on realistic example of integrative structure modeling of the quaternary structure of the actin, tropomyosin, and gelsolin protein assembly based on electron microscopy, solution X-ray scattering, and chemical crosslinking data for the complex as well as excluded volume, sequence connectivity, and rigid atomic X-ray structures of the individual subunits. We follow the general four-stage process for integrative modeling, including gathering the input information, converting the input information into a representation of the system and a scoring function, sampling alternative model configurations guided by the scoring function, and analyzing the results. The computational aspects of this approach are implemented in our open-sourceIntegrative Modeling Platform(IMP), a comprehensive and extensible software package for integrative modeling ( https://integrativemodeling.org ). In particular, we rely on thePython Modeling Interface(PMI) module of IMP that provides facile mixing and matching of macromolecular representations, restraints based on different types of information, sampling algorithms, and analysis including validations of the input data and output models. Finally, we also outline how to deposit an integrative structure and corresponding experimental data into PDB-Dev, the nascent worldwide Protein Data Bank (wwPDB) resource for archiving and disseminating integrative structures ( https://pdb-dev.wwpdb.org ). The example application provides a starting point for a user interested in using IMP for integrative modeling of other biomolecular systems.