Enhancing the Phyre2 protein modelling portal for the community

蛋白质是大分子，是生命的机器。它们是由不同成分组成的长链这些成分的顺序是氨基酸序列。基因组计划正在确定包括植物、动物和微生物在内的许多物种的蛋白质序列。实验方法可以揭示蛋白质的三维结构，这些信息是基本生物学理解的核心，对这些生物学知识的利用对农业、动物福利、健康和生物技术的改进具有重大意义。然而，通常这些基本信息是无法从实验中获得的。生物学家需要计算方法来预测这些信息。Sternberg小组开发了一种功能强大且用户友好的资源，用于从序列预测蛋白质的3D结构。第一个版本是3D-PSSM，最近的版本是Phyre和Phyre2。这是通过网络服务器传播的——用户将他们感兴趣的蛋白质序列粘贴到一个框中，服务器返回预测的3D结构的细节，包括原子坐标和其他信息。事实证明，这一资源特别受全世界科学界的欢迎。已经有超过150万的序列提交到这些服务器，超过3700篇文献引用了描述3D-PSSM和Phyre的三篇主要论文。在美国《自然》、《科学》、《美国国家科学院院刊》等著名期刊上发表了60篇引用Phyre2的论文。Phyre2的用户可以通过帮助页面、视频教程和电子邮件获得帮助。最近我们联系了我们的用户，我们获得了1000多封支持信，这证明了社区对Phyre2的重视。根据我们的电子邮件通信和这些支持信中的信息，我们确定了我们希望对Phyre2网站进行的一系列增强。这笔拨款将为我们维护、支持和增强Phyre2 web服务器以供社区使用提供支持。具体来说，我们建议：1)确保Phyre2门户保持最新和健壮，提供快速周转，并得到对用户的支持。2)通过编制广泛的训练材料（包括个案研究）、提供与每一输出网页动态相连的录象帮助和促进国家、欧洲和世界范围的训练活动来加强用户支助。3)促进Phyre2在生物科学界的广泛应用。4)通过出版物、国内和国际会议演讲以及在英国不同地点提供培训讲习班来传播Phyre2门户网站。5)通过确保Phyre2包含可用的最新建模组件来增强建模。6)实现大规模基因组分析，包括使用任何用户都可以购买的计算资源（称为云计算）提供快速处理设施。7)预测蛋白质上可能发生某些生物学特性的位置，以及蛋白质的哪些区域可能结合与蛋白质功能相关的小分子。8)开发一种令人兴奋和新颖的方法，LogPhyre，在研究蛋白质空间相似区域的Phyre2用户之间建立合作。LogPhyre将确保用户的保密性，并将在用户协议下代理用户之间的连接。9)参与蛋白质结构预测的国际比较评估，如CASP和cameo。10)与我们的科学管理委员会合作，确保我们达到我们的目标，并响应我们不同用户群的需求。11)与包括决策者、博物馆、公众，特别是年轻人在内的不同利益攸关方进行接触。

Proteins are large molecules that are the machinery of life. They are long chains of different components and the order of these components is the amino-acid sequence. The genome projects are now determining the sequences of proteins from many species including plants, animals and microbes. Experimental methods can reveal the 3D structure of a protein, and this information is central to basic biological understanding and the exploitation of this biological knowledge has major implications for improvements in agriculture, animal welfare, health, and biotechnology. However, generally this essential information is not available from experiment. Biologists then require computational methods to predict this information.The Sternberg group has developed a powerful and user-friendly resource for predicting the 3D structure of a protein from its sequence. The first version was 3D-PSSM and the more recent versions are Phyre and Phyre2. This is disseminated via a web server - a user pastes their protein sequence of interest into a box and the server returns details of the predicted 3D structure with atomic coordinates and additional information. This resource has proved exceptionally popular with the world-wide scientific community. There have been over 1.5 million sequence submissions to these servers and over 3,700 literature citations to the three main papers describing 3D-PSSM and Phyre. There are 60 papers citing the use of Phyre2 for their research which have been published in the highly-prestigious journals of Nature, Science and Proceedings of the National Academy of Sciences, USA.Users of Phyre2 are supported by help pages, a video tutorial and e-mail help from us. Recently we contacted our users and we obtained over 1,000 letters of support demonstrating the value the community places on Phyre2. Based on our e-mail correspondence and information within these letters of support we identified a series of enhancements we wish to make to the Phyre2 web site. This grant will provide support for us to maintain, support and enhance the Phyre2 web server for use by the community. Specifically we propose:1) To ensure the Phyre2 portal remains up to date and robust, provides a fast turnaround, and is supported by assistance to users.2) To enhance user support by the development of extensive training material (with case studies), the provision of video help dynamically linked to every output web page and by contributing to national, European and world-wide activities in training.3) To promote the widest use of Phyre2 by the bioscience community. 4) To disseminate the Phyre2 portal via publication, national and international conference presentations, and the provision of training workshops at different sites in the UK.5) To enhance the modelling by ensuring Phyre2 incorporates the very latest modelling components which are available.6) To enable large scale analyses of genomes including the provision of a fast processing facility using computing resources that can be purchased by any user (known as cloud computing). 7) To predict where on a protein certain biological features might occur and which regions of the protein may bind small molecules which are relevant to protein function.8) To develop an exciting and novel approach, LogPhyre, to forge collaborations between Phyre2 users who are studying similar regions of protein space. LogPhyre will ensure user confidentiality and will, with user agreement, broker connections between users.9) To participate in international comparative evaluations of protein structure prediction, known as CASP and CAMEO.10) To work with our scientific management board to ensure we meet our objectives and are responsive the needs of our diverse user base.11) To engage with diverse stakeholders including policy makers, museums, the general public and especially young people.