Center for Critical Assessment of Structure Prediction

 描述(由申请人提供)：该项目为结构预测关键评估(CASP)计划提供使能基础设施，致力于对蛋白质结构建模方法进行客观评估。蛋白质结构的知识对研究大分子的功能、相互作用和生化途径有很大帮助。它还对人类疾病的理解和治疗学的发展产生了重大影响。结构的实验确定本身就是耗时、昂贵的，而且经常遇到不可逾越的障碍。计算建模提供了另一种方法，但建模方法的有效性各不相同，通常不能直接提供精度度量。CASP旨在通过对方法的客观评估来回答这些问题，从而推动进展。CASP是一个社区范围的项目，全球100多个研究小组在上一轮(2014年)提交了超过6万个预测。该中心是CASP的主要基础设施资源，负责处理预测、开发评估软件、执行模型评估、开发分析和显示工具，并促进模型和评估数据的获取。目前的提案包括两个主要的新举措，将CASP的影响扩大到结构生物学的重要新领域。首先，我们将与适当的实验小组合作，开发最大限度地利用稀疏和低分辨率数据的建模方法。核磁共振和交联剂的初步结果证明了这一领域的潜力。第二，与CAPRI倡议(蛋白质相互作用的关键评估)合作，我们将包括生物组装的建模。我们还将继续成功的CASP战略，专注于克服特定的瓶颈问题，如模型精化、模型精度估计和三维接触预测；在同源模型中增加非模板区域的建模。此外，我们将特别强调评估模型在具体生命科学应用中的有用性。最后，我们将与教师和研究人员互动，目的是传播关于建模的见解和通过CASP获得的丰富数据。

 DESCRIPTION (provided by applicant): This project provides the enabling infrastructure for the Critical Assessment of Structure Prediction (CASP) program, dedicated to the objective evaluation of protein structure modeling methods. Knowledge of protein structure significantly aids in the investigation of macromolecular function, interactions, and biochemical pathways. It also has a major impact on the understanding of human disease, and on the development of therapeutics. Experimental determination of structure is inherently time-consuming, costly, and often meets with insurmountable obstacles. Computational modeling offers an alternative approach but modeling methods vary in their effectiveness and typically do not directly provide measures of accuracy. CASP aims at answering these concerns by objective evaluation of methods, so driving progress. CASP is a community-wide program, with over 100 research groups world-wide submitting over 60,000 predictions in the last round (2014). The Center is the primary infrastructure resource for CASP, and handles processing of predictions, develops evaluation software, performs model assessment, develops analysis and display tools, and facilitates access to models and evaluation data. The current proposal includes two major new initiatives, extending the impact of CASP to important new areas of structural biology. First, we will collaborate with appropriate experimental groups to develop modeling methods that maximally leverage sparse and low resolution data. Preliminary results with NMR and crosslinking demonstrate the potential in this area. Second, in partnership with the CAPRI initiative (Critical Assessment of Protein Interactions), we will include modeling of biological assemblies. We will also continue the successful CASP strategy of focusing on overcoming specific bottleneck problems, such as model refinement, estimation of model accuracy, and prediction of three dimensional contacts; adding modeling of non-template regions in homology models. In addition, we will place special emphasis on evaluating the usefulness of models in specific life science applications. Finally, we will interact with teachers and researchers, with te goal of disseminating the insights on modeling and the wealth of data gained through CASP.