The Collaborative Computational Project for NMR (CCPN): Supporting biomolecular NMR and community driven NMR software development.

The Collaborative Computing Project for NMR (CCPN) was started in 2000 to improve the interoperability of software for biomolecular NMR and to promote a collaborative community of software users and programmers. Over the past twelve years, the project has produced the CcpNmr suite of software for interactive NMR data analysis and integration and the CCPN data standard for macromolecular NMR. The software is now used worldwide by >1000 users. Through its conferences and workshops, CCPN also promotes best practices in both computational and experimental aspects of NMR.
With this proposal we seek to continue and further expand the CCPN project and its user community. Building upon the CCPN software platform, new and emerging aspects of NMR and integrative structural biology techniques will now be targeted. For the current period, we aim to:
1. Develop a fully implemented version 3 (v3) of the CCPN software package.
2. Promote and expand the user uptake and user development of the software.
3. Facilitate the use and sharing of state-of-the-art NMR software technology.
4. Strengthen the training of people, sharing of knowledge and exchange of best-practice's by the UK NMR community.

Version 3 of the CcpNmr suite has led to new, user-friendly applications like SpecView and ChemBuild. These are the first CCPN programs to use an entirely new graphical system based on the modern, multi-platform Qt libraries. During the new period, we will bring the same approach to the Analysis and FormatExchange programs. We will ensure that v3 components are easy to use, fully documented and thoroughly tested, with dedicated modules for specialized tasks and means to interact with external programs and services. This will provide flexible tools to support scientific collaborations and advance important areas such as solid state NMR, small molecule screening and metabolomics.

To promote CCPN and increase user uptake, together with our partners we will embed CCPN in a broader range of scientific projects, enhancing its impact in the structural biological community. The greatly enhanced flexibility of the new code will promote dedicated program adaptation to the working procedures of individual laboratories. We plan to use the modular capabilities of CcpNmr v3 and a reorganised library of high-level utility functions to allow for more groups to start writing software for their own specific practices. To ease user uptake a dedicated Analysis Lite, optimized for simplicity rather than for complex problems, will be developed. The CCPN software will be extensively demonstrated through workshops and documentation.

Together with its partners, CCPN will continue the process of software development and integration by means of direct integration of available methods or by using web-based services developed by third parties. Thus, CCPN users will have easy access to a software pipeline for biological NMR, which allows them to proceed smoothly from spectral data via resonance assignment to structure generation and database deposition. CCPN will collaborate with CCISB groups at Harwell to allow NMR to fulfill its role in biophysics and integrated science.

To strengthen the UK NMR community, we will continue the successful series of UK CCPN conferences and teaching programs for (young) researchers. We will also continue the comprehensive help and support for CCPN users and participate in international efforts in knowledge sharing and exchange of best practices by efforts such as WeNMR. We will closely confer with the NMR facilities in Mill Hill, Birmingham and Warwick.

Oversight of the project will be maintained by the CCPN Executive Committee, with representative members from the UK NMR community and CCPN's international Scientific Advisory Board.

The CCPN software is now well established and founded upon a stable UML-based data model. Custom Python scripts are used to generate software libraries (APIs) in Python, Java and C, using storage in XML for Python/C and SQL for Java. These APIs, with their built-in validity checking and backwards and forwards data compatibility, form the basis of the CcpNmr suite of software. The coming period will bring the development of CcpNmr version 3 (v3), including Analysis, Analysis Lite, FormatExchange and integration with 3rd party programs. The new version aims to provide an improved user experience, greater ease of use, customizability and specialization for particular application areas, in part through the use of the faster, more modern Qt graphics library. The v3 software will also provide for user-specified task-oriented layouts that allow customization of the graphical interface, e.g. for solid-state NMR, small molecules or metabolomics. Together with a new high-level subroutine library, this will allow speedy and user-focused 3rd party development of CCPN- enabled software.
We will work closely with our partners in developing software and tools for NMR and other biophysical techniques, to encourage further integration with CCPN software. The CCPN Data Model will be extended as required and we will train developers in the use of the CCPN software libraries. In collaborative scientific projects, we will participate in new avenues in the areas of data analysis, including structure calculations and the use of chemical shifts. We will further develop tools to facilitate access to remote services on the grid, both via web browsers and from inside Analysis.
For interacting with our user base, we will continue to provide the usual fast user support as well as improve our bug tracking and handling. We will continue to run courses for users, including (new) events organised jointly with WeNMR and regularly interact with relevant stakeholders.

The CCPN project is a long-standing, highly-regarded, advanced technological software development and community-building project. Its continued development and maintenance is crucial not only for the field of NMR spectroscopy itself, but also for the larger scientific and societal context. The impact of CCPN is increasingly important as CCPN represents the only fully capable long-lived NMR data-standard and analysis platform. CCPN serves as an example of the acknowledged imperative for the UK to be a leader in the global knowledge economy.

The impact extends to a number of areas:
1. Supporting academic research excellence. The CCPN software package is essential for the research of a large number of UK and worldwide NMR scientists active in the biomedical sciences, including many MRC-funded PIs. Continuing support, improvement and expansion of the software with the latest state-of-the-art tools is essential, as the improved tools developed by CCPN and its partners drives their biomedical NMR-based research programs and stimulates the developments in grid-technology, E-science and -omics type research.

2. Support for industrial innovation and research capacity. Both drug discovery and metabolomics require the development of dedicated software tools. By developing an open- source, readily customizable software platform, CCPN supports industrial innovation, in particular for small- and medium- sized companies that alone cannot afford the development of the technologically demanding NMR technique. The continuing industrial support of CCPN underscores this notion.

3. Providing a scientifically well-trained professional workforce. The presence of a well-educated and technologically skilled workforce is crucial for societal development. CCPN provides direct training for graduate students and post-docs who will soon contribute to the core of the UK technological workforce. By interacting with CCPN at conferences and workshops and by using its technological base, they are trained in scientific thinking, problem solving and scientific software development. These skills are useful much beyond the specific problems they were first applied to and are generally applicable to many problems.

4. Driving technological developments that benefit the UK population through improved health-care.
NMR has emerged as a crucial tool in the quest for dedicated, personalized medicine approaches. Not only does NMR contribute to our understanding of structure and interactions of biomolecules in a variety of states (folded, aggregated, unfolded), NMR-assisted drug discovery has also proved to be one of the leading components in the search for new therapeutic agents, not least in methods for fragment-based lead compound identification. Metabolomics presents a second area of technological development of great potential benefit to the general UK public. Accurate, detailed and timely detection of disease is nearly always beneficial for effective treatment and improves the chances of recovery. NMR has emerged as an excellent tool for the analysis of body fluids and for the attempts to elucidate relevant biomarkers. Specific metabolite patterns are starting to be recognised and correlated with specific disease states. Thus, NMR provides for a great potential as diagnostic tool that will benefit the society at large.

5. Education of the general public. Current high-school students present the future generation of potential scientists. The NMR technique is part of the GCE A- level chemistry curriculum. The CCPN software tools, especially ChemBuild and SpecView, provide for an excellent way to familiarise the students with the curriculum objectives. By providing actual NMR data together with suitable tools and hands-on approaches, we will stir the students' imagination.