Integrated Resource for Protein Recognition Studies

项目摘要 大分子相互作用是细胞过程的基础。这些相互作用的结构表征 对于更好地理解这些过程和我们操纵它们的能力是重要的。的数量 细胞中大分子相互作用的数量明显大于单个大分子的数量。 它们集合体的结构比单个分子的结构更难通过实验确定， 这进一步强调了建模在重建生命过程中的作用。该项目将推动我们的 了解大分子相互作用，并将促进开发更好的工具，他们的建模。 该项目的具体目标是：（1）开发对接技术的资源，（2） 基于知识的对接，以及（3）评估预测的相互作用和卡普里社区范围 实验我们的长期目标是：（a）开发可靠的细胞规模建模资源和工具 大分子相互作用，这将占分子结构和动力学的动态变化， 关联，以及（B）将这些资源和工具应用于细胞的结构建模，这是一个新的前沿和 计算结构生物学的巨大挑战。建议的重点是进一步发展 研究大分子相互作用的综合资源。DOCKS系统将彻底 扩展和多样化，成为细胞过程结构建模的最终资源， 最后是细胞本身。可溶性蛋白质-蛋白质复合物数据库的DOCKESTAL系统将扩展 其他类型的大分子，作为分子识别的知识来源和数据库， 对接程序的资源。资源的核心将包括定期更新和维护的集合 实验确定的大分子复合物。未绑定和建模结构的数据库， 在核心约束集的基础上，将大大扩大和改进，以促进其在全面 为发展对接方法制定基准。对接诱饵数据库将提供 社区范围的评分基准和开发新对接工具的重要资源。 旋转异构体和旋转异构体转移概率的下行模板集和库将是有价值的 数据驱动对接的资源。自动模板集更新程序将维护所有 大分子类型的扩展和多样化的DOCKEMPLESS资源。旋转异构体库和 旋转异构体-旋转异构体的跃迁概率将根据DOCKS集的增长重新计算。 将与卡普里盲测实验共同努力开发自动评估协议。 该资源将整合已开发的数据库和评估协议，并具有方便用户的界面， 结合各种选项，根据各种标准建立定制的综合体，易于访问， 可下载的标准集、可视化和评估工具。

Project Summary Macromolecular interactions are the basis of cellular processes. Structural characterization of these interactions is important for better understanding of these processes and for our ability to manipulate them. The number of macromolecular interactions in a cell is significantly larger than the number of individual macromolecules. Structures of their assemblies are more difficult to determine experimentally than that of the individual molecules, which further emphasizes the role of modeling in reconstruction of life processes. The project will advance our understanding of macromolecular interaction and will facilitate development of better tools for their modeling. The Specific Aims of the project are: (1) Resources for development of docking techniques, (2) Resources for knowledge-based docking, and (3) Assessment of predicted interactions and CAPRI community-wide experiment. Our long-term goals are: (a) development of resources and tools for reliable cell-scale modeling of macromolecular interactions, which will account for dynamic changes in the molecular structures and kinetics of association, and (b) application of these resources and tools to structural modeling of a cell, a new frontier and a grand challenge of computational structural biology. The focus of the proposal is further development of the integrated resource for studying macromolecular interactions. The DOCKGROUND system will be radically expanded and diversified to become an ultimate resource for structural modeling of cellular processes, and eventually the cell itself. The DOCKGROUND system of databases of soluble protein-protein complexes will extend to other types of macromolecules, to serve as a source of knowledge on molecular recognition and a data resource for docking procedures. The core of the resource will consist of regularly updated and maintained sets of experimentally determined macromolecular complexes. The databases of unbound and modeled structures, built upon the core bound set, will be significantly expanded and improved to advance their role in comprehensive benchmarking for the development of docking methodologies. The database of docking decoys will provide community-wide scoring benchmark and an important resource for development of new docking tools. Downloadable template sets and libraries of rotamers and rotamer transition probabilities will be valuable resources for data-driven docking. The automated template set updater will maintain the template sets for all types of macromolecules in the expanded and diversified DOCKGROUND resource. The rotamer libraries and rotamer-rotamer transition probabilities will be recalculated according to the growth of the DOCKGROUND sets. Automated assessment protocols will be developed in a joint effort with the CAPRI blind prediction experiment. The resource will integrate the developed databases and assessment protocols, with a user-friendly interface, combining options to build customized sets of complexes based on various criteria, easily accessible and downloadable standard sets, visualization, and assessment tools.