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要瓶颈。我们开发了一个数据挖掘框架，PROSPERO，可以预测结晶成功和晶体衍射质量的基础上，大规模结晶试验之前可用的特定蛋白质特性的表征。这将提高单个研究项目以及基因组规模项目衍射研究的效率和总体成功率。PROSPERO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征是，它可以基于底层数据库的当前内容以及个体用户提供的物理表征数据集来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），用于向核心数据存储，元分析和预测组件提供新的数据类别。这将使PROSPERO的使用量身定制的个人研究计划，目标特定的物理特性，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，该社区将受益于中央PROSPERO网络服务器所做的不断改进的预测，该网络服务器将根据标准实验室协议和仪器产生的数据贡献新的输入模块，并且还将有助于预测所用结果的基础数据库的人口。 公共卫生相关性：X射线晶体学是基础研究项目的核心技术，这些项目旨在了解基于单个蛋白质、大型多蛋白质复合物以及蛋白质和核酸组装成细胞关键组分的三维结构的疾病机制。它也是高度针对性的研究项目（如新药设计）的核心技术。这项工作将通过改善一个关键瓶颈，即获得所研究生物实体的高质量晶体的困难，提高这些研究项目的效率和总体成功率。

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.