Prediction of Protein Crystallization and Diffraction Quality

描述（由申请人提供）：鉴于晶体学在结构生物学中的关键作用，蛋白质结晶仍然是影响广泛研究计划的重大瓶颈。我们开发了一个数据挖掘框架，PROSPERO，它可以在大规模结晶试验之前基于特定蛋白质特性的表征来预测结晶成功和晶体衍射质量。这将提高单个研究项目以及基因组规模项目的衍射研究的效率和总体成功率。普洛斯彼罗将基于统计和机器学习方法对许多个体预测因子进行荟萃分析。该框架的一个关键特性是，它可以根据底层数据库的当前内容和单个用户提供的物理特征数据集动态地重新估计成功/失败率。设计将是模块化的，因为我们将定义一组标准的应用程序接口（api），为核心数据存储、元分析和预测组件提供新的数据类别。这将允许使用普洛斯彼罗量身定制的个人研究项目，目标特定的物理性质，并纳入新的物理表征技术。我们的长期目标是发展一个用户社区，这个社区将受益于中央PROSPERO web服务器不断改进的预测，它将根据标准实验室协议和设备产生的数据提供新的输入模块，并将为用于预测的结果基础数据库的人口做出贡献。

DESCRIPTION (provided by applicant): Given the key role that crystallography plays in structural biology, protein crystallization remains a significant bottleneck affecting a broad range of research programs. We developing a data-mining framework, PROSPERO, that can predict crystallization success and crystal diffraction quality based on characterization of specific protein properties available prior to large-scale crystallization trials. This will increase the efficiency and overall success rates of diffraction studies by individual research programs as well as by genome-scale projects. PROSPERO will perform a meta-analysis of many individual predictors based on statistical and machine-learning methods. A key feature of this framework is that it can dynamically re-estimate success/failure rates based on the current contents of the underlying database, and on the set of physical characterization data provided by individual users. The design will be modular, in that we will define a standard set of application interfaces (APIs) for supplying new categories of data to the core data storage, meta-analysis and prediction components. This will allow use of PROSPERO to be tailored to individual research programs, to target-specific physical properties, and to incorporate new physical characterization techniques. Our long-term goal is to grow a user community that will benefit from the continually improving predictions made by a central PROSPERO web server, that will contribute new input modules based on data produced by standard laboratory protocols and apparatus, and will also contribute to the population of the underlying database of results used for prediction. PUBLIC HEALTH RELEVANCE: X-ray crystallography is a core technique in fundamental research programs that seek to understand disease mechanisms based on the three-dimensional structure of individual proteins, of large multi-protein complexes, and of larger assemblies of proteins and nucleic acids into key components of the cell. It is also a core technique in highly targeted research programs such as the design of new drugs. This work will increase the efficiency and overall success rate of these research programs by ameliorating a key bottleneck, the difficulty of obtaining high-quality crystals of the biological entity being studied.