Integrated Resource for Protein Recognition Studies

描述(申请人提供)：蛋白质-蛋白质对接问题是计算结构生物学中的活动焦点之一。蛋白质-蛋白质的三维结构 一般来说，复合体比单个蛋白质的结构更难通过实验确定。由于已知蛋白质3D结构的数量不断增加，特别是在结构基因组学的背景下，足够的计算技术来模拟蛋白质相互作用是重要的。该项目将提高我们对蛋白质相互作用基本性质的理解，并将促进开发更好的工具来预测 蛋白质复合体。该项目的具体目标是：(1)蛋白质识别数据资源，(2)先进的对接方法，(3)基于网络的综合环境。长期目标是：(A)开发一种对蛋白质相互作用进行可靠建模的自动化工具，这将考虑到蛋白质相互作用的分子结构和动力学的动态变化，以及(B)利用这一工具来理解蛋白质相互作用的原理。最终目标是在基因组中重建蛋白质相互作用的网络，并了解这些相互作用的基于结构的机制。对这些相互作用的系统、详细的描述将在分子水平上提供对生命过程的基本原理的洞察。该提案的重点是研究蛋白质-蛋白质3D相互作用的综合资源系统。核心数据集包括定期更新和注释的蛋白质-蛋白质共结晶结构。实验确定的和模拟的未结合络合物的数据库将在核心数据集上进一步扩展。它将成为对接技术发展的综合基准。蛋白质模型复合体数据库将为发展蛋白质建模的对接能力，包括全基因组研究，提供核心数据集的独特扩展。对接诱饵将为新的计分功能提供社区范围的试验场。对接程序将进一步发展，使其更适合于蛋白质-蛋白质复合体结构建模的挑战。这项开发将利用快速增长的实验确定的蛋白质-蛋白质复合体结构。对接方法将利用有关蛋白质靶标的现有知识，并改进结构和物理化学识别因子的使用。将利用界面旋转体库和构象转变概率，系统地探索对接在结构表示、能量函数和采样方面的粗粒化。对接 程序和相关数据库将继续作为网上公共资源提供。

DESCRIPTION (provided by applicant): The protein-protein docking problem is one of the focal points of activity in computational structural biology. The 3D structure of a protein-protein complex, generally, is more difficult to determine experimentally than the structure of an individual protein. Adequate computational techniques to model protein interactions are important because of the growing number of known protein 3D structures, particularly in the context of structural genomics. The project will improve our understanding of fundamental properties of protein interaction and will facilitate development of better tools for prediction of protein complexes. The Specific Aims of the project are: (1) Protein recognition data resources, (2) Advanced docking methodology, and (3) Integrated web-based environment. The long-term goals are: (a) development of an automated tool for a reliable modeling of protein interactions, which will account for dynamic changes in the molecular structures and kinetics of protein association and (b) utilization of this tool to understand principles of protein interaction. The ultimate goal is to recreate the network of protein interactions in genomes and understand the structure-base mechanisms of these interactions. The systematic, detailed description of these interactions will provide insights into the basic principles of life processes at the molecular levl. The focus of the proposal is an integrated system of resources for studying protein-protein 3D interactions. The core dataset consists of regularly updated and annotated co-crystallized protein-protein structures. The database of experimentally determined and simulated unbound complexes will be further expanded upon the core dataset. It will serve as a comprehensive benchmark set for the development of docking techniques. The database of complexes of protein models will provide a unique expansion of the core dataset for the development of docking capabilities in protein modeling, including genome-wide studies. The docking decoys will provide the community-wide testing ground for new scoring functions. The docking procedure will be developed further to make it more adequate to the challenges of structural modeling of protein-protein complexes. The development will make use of the rapidly growing body of experimentally determined structures of protein-protein complexes. The docking methods will utilize available knowledge on the protein targets, combined with the improved use of structural and physicochemical recognition factors. Coarse-graining of the docking in terms of structural representation, energy function, and sampling will be systematically explored, making use of the interface rotamer libraries and probabilities of conformational transitions. The docking procedure and the related databases will continue to be provided as a web-based public resource.