Prediction of Protein Crystallization and Diffraction Quality

描述(申请人提供)：鉴于结晶学在结构生物学中扮演的关键角色，蛋白质结晶仍然是影响广泛研究项目的一个重要瓶颈。我们开发了一个数据挖掘框架Propero，它可以根据大规模结晶试验之前可用的特定蛋白质属性的表征来预测结晶成功和晶体衍射质量。这将提高通过个别研究项目和基因组规模项目进行的绕射研究的效率和总体成功率。普罗斯佩罗将基于统计和机器学习方法对许多单独的预测因素进行荟萃分析。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由个人用户提供的一组物理特征数据来动态地重新估计成功率/失败率。设计将是模块化的，因为我们将定义一套标准的应用程序接口(API)，用于向核心数据存储、荟萃分析和预测组件提供新的数据类别。这将允许根据个人研究计划、特定于目标的物理特性以及结合新的物理表征技术来使用Prosman o。我们的长期目标是发展一个用户群体，该群体将受益于一个中央Propero网络服务器作出的持续改进的预测，该服务器将基于标准实验室协议和仪器产生的数据提供新的输入模块，并将有助于用于预测的底层结果数据库的填充。 与公共健康相关：X射线结晶学是基础研究项目中的一项核心技术，这些项目寻求基于单个蛋白质的三维结构、大型多蛋白质复合体以及更大的蛋白质和核酸组装成细胞关键组件的三维结构来了解疾病机制。它也是新药设计等具有高度针对性的研究项目的核心技术。这项工作将通过改善一个关键的瓶颈，即获得高质量的生物实体晶体的难度，来提高这些研究计划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.