Algorithm and Web Server for Low-homology Protein Threading

位于芝加哥的丰田技术研究所获得了一笔赠款，通过利用NSF赞助的网络基础设施开放科学网格(OSG)，开发了一种长期可持续的低同源性蛋白质线程网络服务器。OSG已被证明在许多研究领域非常有用，包括蛋白质折叠、蛋白质对接、地球科学和粒子物理。本研究的具体目标是：(1)开发一个公共的蛋白质线索网络服务器，可以在几分钟内将单个蛋白质序列串接到整个模板库，从而为大量的用户提供服务。服务器将使用OSG作为后端计算引擎，它可以轻松地将数百万个作业分配给美国各地的超级计算机，因此我们的服务器可以在数千个CPU上免费运行作业，而且我们还可以轻松地在这个项目的资金期之后几乎免费地对服务器进行长期维护。(2)通过在服务器中加入依赖于轮廓熵的评分功能来定制专用于低同源性蛋白质线程的网络服务器。该服务器将显著提高低同源性蛋白质的建模能力，而现有的蛋白质建模程序无法针对这些蛋白质生成良好的模型。该项目开发的服务器将帮助个体生物学家和经验丰富的生物信息学团队分析没有解决结构的蛋白质的结构和功能，特别是那些来自元基因组数据的低同源性蛋白质。这个蛋白质建模网络服务最终将通过为替代能源和新药等应用研究领域提供必要的基础设施而造福公众。通过开发一个由OSG授权的长期可持续的网络服务器，该项目将促进NSF赞助的网络基础设施在科学研究中的应用。整个项目的开发、实施和评估还将促进与结构生物信息学和分布式/网格计算相关的知识的及时和有效传播，并将培养基础生物科学和高级计算技术的学生。

The Toyota Technological Institute at Chicago is awarded a grant to develop a long-term sustainable web server for low-homology protein threading by making use of the NSF-sponsored cyberinfrastructure Open Science Grid (OSG). The OSG has been proved to be very useful in many research areas including protein folding, protein docking, geoscience and particle physics . The specific goals of this research are: (1) To develop a public protein threading web server that can thread a single protein sequence to the whole template database within minutes and thus, provide service to a large number of users. The server will use OSG, which can easily distribute millions of jobs to the supercomputers around USA, as the back-end computing engine so that our server can run jobs on thousands of CPUs free of charge and we can also easily maintain the server in the very long term beyond the funding period of this project at almost no cost. (2) To customize the web server specifically for low-homology protein threading by incorporating a profile-entropy dependent scoring function into the server. The server will significantly improve modeling capability of low-homology proteins, for which existing protein modeling programs cannot generate good models. The server developed by this project will help both individual biologists and experienced bioinformatics teams analyze the structure and function of proteins without solved structures, especially those low-homology proteins from metagenomic data. This protein modeling web service will ultimately benefit the public by providing a necessary infrastructure for applied areas of study such as alternative energy sources and new medicines.By developing a long-term sustainable web server empowered by the OSG, this project will promote the application of the NSF-sponsored cyberinfrastructure to scientific research. The development, implementation, and evaluation of the whole project will also promote the timely and effective knowledge dissemination related to structure bioinformatics and distributed/grid computing and will train students in both basic biological sciences and advanced computing techniques.