Enhancing the Phyre2 protein modelling portal for the community

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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.