ABI Development: Continued Development of RaptorX Server for Protein Structure and Functional Prediction

高通量测序已经产生了数百万个没有解决结构和功能注释的蛋白质序列，这增加了对计算工具的需求，特别是用于蛋白质结构和功能阐明的用户友好的网络服务器。这个项目将把RaptorX，一个流行的蛋白质结构建模网络服务器，改造成一个在没有相应的天然结构的情况下，也可以注释蛋白质序列的功能和理论蛋白质模型的质量的服务器。由此产生的新服务器将极大地促进对理论蛋白质模型的解释和正确使用，就像E-Value为同源搜索所做的那样。该服务器还将预测蛋白质序列的功能，其覆盖范围超出了基于天然结构的方法所能达到的范围，并且精度远远高于基于序列的方法。最终，该项目将为蛋白质序列、结构和功能分析提供长期可持续的网络基础设施，从而能够进行变革性的生物和生物医学研究。该项目还将通过开发几种用于模型质量评估和功能预测的复杂计算方法来推进蛋白质结构和功能预测。蛋白质在所有的生物过程中都扮演着基本的角色。对蛋白质结构和功能的完整描述是了解生物生命的基本步骤。该项目将有益于广泛的生物/生物医学应用，如植物代谢途径的研究、药物设计和生物能源开发。研究成果将通过各种场所(维基、演讲、论文和海报)传达给更广泛的社区。该软件将免费向公众开放。自2011年8月首次发布以来，RaptorX已经为全球超过3500名用户处理了数万项蛋白质建模和分析工作。在新的RaptorX实施后，它将为更广泛的社区做出更大的贡献。该项目还将通过研究受蛋白质生物信息学启发的机器学习问题，为计算机科学做出贡献。该项目将丰富和传播蛋白质生物信息学、机器学习和网络编程方面的知识。它还将培训少数族裔学生、未来的K-12科学教师和伊利诺伊州在线生物信息学项目的全国学生。所有参与的学生都将接受计算机科学、分子生物学、生物物理学和生物化学交叉学科的培训。研究成果将被整合到课程材料中，这些材料将在课堂上使用，并向公众免费提供。

High-throughput sequencing has been producing millions of protein sequences without solved structures and functional annotations, which raise demand for computational tools especially user-friendly web servers for protein structure and functional elucidation. This project will transform RaptorX, a popular protein structure modeling web server, to one that can also annotate functions of a protein sequence and the quality of a theoretical protein model in the absence of the corresponding native structure. The resultant new server will greatly facilitate the interpretation and proper usage of a theoretical protein model, just like what E-value does for homology search. The server will also predict functions of a protein sequence with coverage beyond what can be reached by native-structure-based methods and accuracy much higher than sequence-based methods. Ultimately, the project will deliver a long-term sustainable cyber-infrastructure for protein sequence, structure and functional analysis that enables transformative biological and biomedical research. This project will also advance protein structure and functional prediction by developing several sophisticated computational methods for model quality assessment and functional prediction. Proteins play fundamental roles in all biological processes. Complete description of protein structures and functions is a fundamental step towards understanding biological life. This project will benefit a broad range of biological/biomedical applications, such as the study of plant metabolic pathways, drug design, and bio-energy development. The research results will be communicated to the broader community through a variety of venues (wiki, talks, papers and posters). The software will be freely available to the public. Since its first release in August 2011, RaptorX has processed dozens of thousands of protein modeling and analysis jobs for more than 3500 users around the world. After the new RaptorX is implemented, it will contribute much more to the broader community. This project will also contribute to computer science by studying machine learning problems inspired from protein bioinformatics. This project shall enrich and disseminate knowledge on protein bioinformatics, machine learning and web programming. It will also train minority students, future K-12 science teachers and nationwide students in the Illinois online bioinformatics program. All involved students will receive training in the intersection of computer science, molecular biology, biophysics, and biochemistry. The research results will be integrated into course materials, which will be used in the classes and also freely available to the public.