Integrated Resource for Protein Recognition Studies

描述（由申请人提供）：蛋白质-蛋白质对接问题是计算结构生物学活动的焦点之一。蛋白质-蛋白质复合物的3D结构通常比单个蛋白质的结构更难通过实验确定。适当的计算技术来模拟蛋白质的相互作用是很重要的，因为越来越多的已知蛋白质的三维结构，特别是在结构基因组学的背景下。该项目将提高我们对蛋白质相互作用的基本性质的理解，并将促进开发更好的预测蛋白质复合物的工具。该项目的具体目标是：（1）开发先进的对接算法，（2）蛋白质-蛋白质共结晶结构数据库，（3）蛋白质-蛋白质模拟未结合结构数据库，（4）蛋白质-蛋白质模型数据库，（5）对接诱饵数据库，以及（6）基于网络的蛋白质识别研究公共资源。长期目标是：（a）开发一种自动化工具，用于蛋白质相互作用的可靠建模，这将解释蛋白质缔合的分子结构和动力学的动态变化，以及（B）利用该工具来理解蛋白质相互作用的原理。最终目标是重建基因组中蛋白质相互作用的网络，并了解这些相互作用的结构基础机制。对这些相互作用的系统而详细的描述将提供对分子水平上生命过程的基本原理的深入了解。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。现有的对接程序将进一步发展，使其更适合蛋白质-蛋白质复合物的结构建模的挑战。该程序将用于生成对接数据集，以开发建模能力。核心数据集将由共结晶蛋白质-蛋白质结构组成。该数据集将具有根据序列和结构相似性排除冗余的选项。将定期更新和附加说明。模拟未结合复合物的数据库将建立在核心数据集上。它将成为发展对接技术的一套全面基准。蛋白质-蛋白质模型数据库将为开发蛋白质建模（包括全基因组研究）中的对接能力提供核心数据集的独特扩展。对接诱饵数据库将为新的评分功能提供社区范围的试验场。

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) development of an advanced docking algorithm, (2) database of protein-protein co-crystallized structures, (3) database of protein-protein simulated unbound structures, (4) database of protein-protein models, (5) database of docking decoys, and (6) integrated web-based public resource for studying protein recognition. 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 level. The focus of the proposal is an integrated system of resources for studying protein-protein 3D interactions. An existing docking procedure will be developed further to make it more adequate to the challenges of structural modeling of protein-protein complexes. The procedure will be used to generate the docking datasets for the development of modeling capabilities. The core dataset will consist of co-crystallized protein-protein structures. The dataset will have options to exclude redundancies based on sequence and structure similarities. It will be regularly updated and annotated. The database of simulated unbound complexes will be built upon the core dataset. It will serve as a comprehensive benchmark set for the development of docking techniques. The database of protein-protein models will provide a unique expansion of the core dataset for development of docking capabilities in protein modeling, including genome-wide studies. The database of docking decoys will provide the community-wide testing ground for new scoring functions.