CCP4 Advanced integrated approaches to macromolecular structure determination
Lead Research Organisation:
University of Southampton
Department Name: Sch of Biological Sciences
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Planned Impact
The CCP4 software suite has a wide national and international distribution with over 20,000 academic and over 160 commercial licenses worldwide. The proposal realises the impacts
(1) in education through active involvement of developers in teaching and outreach activities, and through the networking of programmers and users of crystallography software, creating career opportunity for programmes and developers;
(2) in the scientific community by cross-fertilisation across scientific disciplines where crystallography is used and the CCP4 software is applied, and further by driving methods development, thus leveraging investment in scientific infrastructures;
(3) in the UK economy by impacting stakeholders in academic spin-out and industry, and directly through engaging industrial users in working groups and executive committee;
(4) in society by generating commercial and economic revenue, mainlining a leading role for UK-PLC in a globalised setting.
Dissemination and impact activities are steered by two working groups; working group chairs report to the CCP4 executive committee to manages software development and ensures scientific leadership. Working group 2 is essential for community building, making world leading computational methods accessible to academia, groups new to crystallography, and industrial users. The working group bridges between users of the software, PIs in the crystallography field and beyond, the CCP4 core developers' team, programmers and developers, and furthers association with new talent. This proposal recognises the critical role of working group 2 in steering or participating in the following activities to maximise impact, as outlined in the 2014 preamble:
+ CCP4's working groups are constituted from users, core team and developers. Working group 2 provides input to keep the software at the forefront of development, constantly challenging its use. The executive committee oversees integration of new software into the suite, and the CCP4 core team maintain the high standards, ensure compatibility and future-proof nature of the suite, and drive new software solutions.
+ The annual study weekend, organisation of which is overseen by working group 2, is central to dissemination of the software and brings together users, notably ECRs, PostDocs, GradStudents, programmers and developers; it serves a significant role in education and road testing as well as gathering of user requirements and nurturing talent.
+ The annual CCP4 special issue features new science generated from the annual study weekend and attracts many citations; it serves in dissemination and peer review and has become a community reference, increasing the GPA of researchers / developers contributing to CCP4. Further dissemination activities include documentation, teaching activities and tutorials, web page, and the CCP4 bulletin board as an online-tool widely used by the worldwide community to exchange information and to report or resolve problems directly or indirectly linked to the CCP4 software.
+ The annual developers retreat nurtures cross-fertilisation between developers that are directly funded or are affiliated with CCP4 activities (including PDB or CRYO EM) to enable community response to challenges identified by the executive committee.
+ Sponsoring of national outreach events and holding national workshops / schools reaches out young scientists, generates new networks, and brings in new talent; commercial licenses generate revenue to support these outreach and training events. Participation in international conferences and holding international workshops engages the community and raises an international profile to increases reputation.
+ CCP4 offers competitive funding of projects through an internal bidding process and supports external grant application through the executive committee.
(1) in education through active involvement of developers in teaching and outreach activities, and through the networking of programmers and users of crystallography software, creating career opportunity for programmes and developers;
(2) in the scientific community by cross-fertilisation across scientific disciplines where crystallography is used and the CCP4 software is applied, and further by driving methods development, thus leveraging investment in scientific infrastructures;
(3) in the UK economy by impacting stakeholders in academic spin-out and industry, and directly through engaging industrial users in working groups and executive committee;
(4) in society by generating commercial and economic revenue, mainlining a leading role for UK-PLC in a globalised setting.
Dissemination and impact activities are steered by two working groups; working group chairs report to the CCP4 executive committee to manages software development and ensures scientific leadership. Working group 2 is essential for community building, making world leading computational methods accessible to academia, groups new to crystallography, and industrial users. The working group bridges between users of the software, PIs in the crystallography field and beyond, the CCP4 core developers' team, programmers and developers, and furthers association with new talent. This proposal recognises the critical role of working group 2 in steering or participating in the following activities to maximise impact, as outlined in the 2014 preamble:
+ CCP4's working groups are constituted from users, core team and developers. Working group 2 provides input to keep the software at the forefront of development, constantly challenging its use. The executive committee oversees integration of new software into the suite, and the CCP4 core team maintain the high standards, ensure compatibility and future-proof nature of the suite, and drive new software solutions.
+ The annual study weekend, organisation of which is overseen by working group 2, is central to dissemination of the software and brings together users, notably ECRs, PostDocs, GradStudents, programmers and developers; it serves a significant role in education and road testing as well as gathering of user requirements and nurturing talent.
+ The annual CCP4 special issue features new science generated from the annual study weekend and attracts many citations; it serves in dissemination and peer review and has become a community reference, increasing the GPA of researchers / developers contributing to CCP4. Further dissemination activities include documentation, teaching activities and tutorials, web page, and the CCP4 bulletin board as an online-tool widely used by the worldwide community to exchange information and to report or resolve problems directly or indirectly linked to the CCP4 software.
+ The annual developers retreat nurtures cross-fertilisation between developers that are directly funded or are affiliated with CCP4 activities (including PDB or CRYO EM) to enable community response to challenges identified by the executive committee.
+ Sponsoring of national outreach events and holding national workshops / schools reaches out young scientists, generates new networks, and brings in new talent; commercial licenses generate revenue to support these outreach and training events. Participation in international conferences and holding international workshops engages the community and raises an international profile to increases reputation.
+ CCP4 offers competitive funding of projects through an internal bidding process and supports external grant application through the executive committee.
Publications
Agirre J
(2023)
The CCP 4 suite: integrative software for macromolecular crystallography
in Acta Crystallographica Section D Structural Biology
Beale JH
(2019)
Successful sample preparation for serial crystallography experiments.
in Journal of applied crystallography
Horrell S
(2021)
Fixed Target Serial Data Collection at Diamond Light Source.
in Journal of visualized experiments : JoVE
Krissinel E
(2022)
CCP4 Cloud for structure determination and project management in macromolecular crystallography.
in Acta crystallographica. Section D, Structural biology
Lucic M
(2020)
Serial Femtosecond Zero Dose Crystallography Captures a Water-Free Distal Heme Site in a Dye-Decolorising Peroxidase to Reveal a Catalytic Role for an Arginine in FeIV =O Formation.
in Angewandte Chemie (International ed. in English)
Moreno-Chicano T
(2022)
Complementarity of neutron, XFEL and synchrotron crystallography for defining the structures of metalloenzymes at room temperature.
in IUCrJ
Storm SLS
(2020)
Measuring energy-dependent photoelectron escape in microcrystals.
in IUCrJ
| Description | 1. The CCP4 web pages were redesigned and released 2, Four WG2 meetings held on 29.1./29.6./30.7./24.9.20, dealing with CCP4 housekeeping such as core group activities and developments, workshops, online meetings, Publication of the Acta Cyrstallographica special issue, and web presence, as well as novel software developments and user input to software development 3. Organisation of the South Western Structural Biology Conference (SWSC) "online" 20-21.7.20 that served as a test run for the online SW2021 4. Delivery of the CCP4 Study Weekend "Integrating Structural Biology" 5-8.1.2021 online |
| Exploitation Route | Special Issue and Web Pages are a valuable resource for future research WG2, SWSBC and SW2021 are dissemination activities |
| Sectors | Digital/Communication/Information Technologies (including Software),Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
| URL | https://www.ccp4.ac.uk |
| Description | Appointment of an ED&I team for CCP4 |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Membership of a guideline committee |
| Description | CCP4 DOCUMENTATION PROJECT |
| Organisation | Science and Technologies Facilities Council (STFC) |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Acquisition of the contract through the CCP4 industrial funds mechanisms and supervision of Maria Fando, PDRA. Weekly meetings and steering of the project. - STFC has assembled the CCP4 suite of software applications and libraries with support from the Biotechnology and Biological Sciences Research Council, as part of the Collaborative Computational Project Number 4 (CCP4). - The University holds a grant to raise the impact of CCP4 that includes development of documentation that is suitable for inclusion in the CCP4 suite (award reference BB/S008470/1). - STFC will own the Intellectual Property Rights in the Software. |
| Collaborator Contribution | CCP4 offers program-specific descriptions distributed with the software, typically provided by developers. Newly written GUI specific documentation is available through the interfaces in ccp4i2, CCP4 Cloud and ccp4-online structure solution services. Descriptions may be front-end specific, and they are often technical or task-oriented. Proposed work: You will screen and revise resources from a user perspective to adapt existing documentation to common style. This project provides users with appropriate, consistent and modern-style documentation. A reStructuredText (RST) platform, hosted on a git repository, will be used for development of documentation to unify information across all front-ends. The post links up with efforts from developers for technical solutions, and crystallography experts for advanced technique details. Aims: This project integrates into the CCP4 impact proposal and aims to provide users with a consistent view of computational crystallography, which, being integrated with tutorial materials, will lead to establishing the Suite as a system for learning crystallography. Background. CCP4 used to have a central resource with program documentation for the 50+ programs that were constituent of the original suite in the 90's. Further, there was a manual to guide the user along the steps of a crystal structure determination using the CCP4 software. Many programs have now been added, new techniques and tricks appeared, and modern GUIs have been developed. This has led to today's situation where we find CCP4 documentation fragmented and distributed, and not fit for purpose. Proposal. It is proposed to develop user documentation by combining into single source, adapting the user perspective. This enables migration from current developer-based document versions and fills gaps in the available documentation. With the generation of a uniform bundle this project produces a central resource for the various CCP4 front-ends that can easily be adapted, extended and maintained. The project will therefore influence and drive implementation and use of documentation into the GUIs. The generalised documentation contents will be delivered as a cross-linked HTML bundle, using reStructuredText (RST) formatted source files. Compilation is automated and implemented as a part of CCP4 build pipeline, allowing dynamic updates via the present CCP4 update mechanism. End-user distribution occurs web-browser supported and uniformly for present and future front-ends, to include ccp4i2, CCP4 Cloud and CCP4 online1. Further, invoking the documentation from command line program use via a local or a web link can be explored to give a similar feel across all levels of program use2. Central to the concept of an integrated documentation across the CCP4 front-ends is further accessibility of the same information from the new CCP4 web-pages. From within the GUIs, the proposed approach enables to link technical support (e.g. buttons to press, file info, ...) with functionality of the software. Further, it enables users to learn about the underlying scientific concepts. An integrated documentation is necessary to allow the user community to appreciate the full depth of programs and their use. To link documentation directly with the use of programs enables intelligent and advanced use of the software. Outlook. The target of this project is to establish an easy to access, navigate and modify base of CCP4 documentation. Integration of a documentation resource that is developed and maintained centrally is a necessity. Clear gains are that this resource is easily maintained, uniform across the suite, and can be kept up to date. Further benefits are evident. Worked examples are a good tool to guide the user experience and to provoke the use of advanced features, advancing the lead of the software in the field. CCP4 already has a good resource of tutorials, and these can be linked in with the documentation resource. Together, documentation and tutorials provide a framework to deliver a learning experience for crystallography. This proposal enables an excellent platform for learning and teaching crystallography, and might even open a route to a new CCP4 user manual. Notes 1Distribution to ccp4i2 occurs via the built-in Qt5-based browser and is dependent on a version update due to be released in the beginning of 2021. 2Technical implementation for command line documentation use will require novel code. ? Month 1: Existing CCP4 documentation sighted and categorised into parts of o CCP4i2 specific o CCP4 Cloud specific o CCP4-online specific o Common relevance ? Month 2: Documentation structures for CCP4i2, Cloud and ccp4-online designed, and the corresponding packages created in gitlab repository(-ies), with necessary cross-links, references, and common parts re-used ? Month 3: Documentation building and deployment procedures agreed with relevant CCP4 developers and implemented as necessary ? Month 4-5: Documentation gaps, identified in 1st month, filled ? Month 6: Prototype educational resources, integrating demo data, projects and documentation, created for most commonly used structure solution techniques |
| Impact | The documentation project directly contributes to the software and is fully included in the CCP4 distribution. Further, tutorials for use of the software were developed as a crystallography learning system. |
| Start Year | 2021 |
| Description | Serial Data Processing and Analysis in CCP4i2 |
| Organisation | Science and Technologies Facilities Council (STFC) |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | CCP4i2 offers entry points for single or multiple crystal (rotation) diffraction data. However, there is no entry point for serial data recorded Synchrotron (SSX) or XFEL (SFX) sources, other than a merged mtz file. This leads to scarcity of engaging with this novel type of data. The collaboration between the host laboratory, CCP4, the Diamond Light Source, generates capability of treating and analysing serial data in CCP4i2 will allow the user to interact with integrated data, amongst others Dials and crystFEL ascii files reflection files. Provision of analytical tools will allow decision making and iterative improvement of merging/scaling to generate custom datasets. Aims: We will add two elements to CCP4i2: (a) data entry point for integrated serial data; (b) pipelines with analytical tools and branch-points for user intervention for these data for downstream processing by the suite. |
| Collaborator Contribution | Background. Serial data processing techniques are perceived as specialist method, though these types of data are now becoming commonplace. This would include XFEL sources (SFX), but notably novel synchrotron capability (SSX). Interacting with such data in CCP4 is hampered as tools for true serial data are only found outside the CCP4 environment. This project engages with integrated serial data. Analytical tools are needed for a crystallographic target driven approach (potentially enabling user friendly real-time feedback through integration into the beamline infrastructure) to produce datasets that answer to requirements of unit cell isomorphousness, processing stats, map quality, ligand occupancy, or other. This proposal makes CCP4 central to serial data analysis and will allow processing of these complex experiments for all users with crystallographic background. Proposal. Capability to process serial data, using Dials and newly developed analytical tools: • create a XIA2-like experience to produce datasets • target driven (e.g. resolution) scaling and merging (user interfaced / automatic) • intelligent decision-making about resolution limits (compare aimless approach) • tools to identify well performing samples / runs / frames (post data collection) • assessment of data quality for different end applications thus creating ability to pipe results through to downstream applications assisting with the processing to improve stats / maps against target parameters (e.g. map quality, ligand, ) This proposal integrates across the Dials and CCP4 teams, with implementation in CCP4i2. The post is part-hosted at the Diamond beamline I24 which offers opportunity to engage with serial data. Fast sample delivery reduces the per-dataset time and rapidly increases the quantity of data being collected, putting in a demand for on-the-fly capability to influence choice of data collection parameters / targets, which this proposal explores. Ability to feed a test dataset and set up a processing system is part of beamline specific integration of the workflow. Multiple serial crystallographic SR beam lines are either operational or in development, and it may be possible to make the workflow in processing and analytics adaptable to other beamlines used in serial data collection. The collaboraton is to deliver initial capability for SSX, making this type of data easily available from within CCP4, by interfacing with CCP4i2. |
| Impact | The first interface has been programmed and shall be rolled out with one of the next CCP4 releases. Computer Science, Life Sciences, Chemistry |
| Start Year | 2023 |
| Title | CCP4 Web Pages |
| Description | Web Pages for CCP4 |
| Type Of Technology | Webtool/Application |
| Year Produced | 2019 |
| Open Source License? | Yes |
| Impact | The new web pages are developed with WordPress and completely revise the presentation of the CCP4 project and software. Released June 2020. |
| URL | https://www.ccp4.ac.uk |
| Title | The CCP4 Documentation Project |
| Description | The CCP4 Documentation Project See contract with external partner. license: https://www.ccp4.ac.uk/licensing/academic_software_licence.pdf |
| Type Of Technology | New Material/Compound |
| Year Produced | 2021 |
| Impact | This project integrates into the CCP4 impact proposal and aims to provide users with a consistent view of computational crystallography, which, being integrated with tutorial materials, will lead to establishing the CCP4 Suite as a learning system in crystallography. |
| URL | https://cloud.ccp4.ac.uk/manuals/html-taskref/index.html# |
| Description | CCP4 study weekend |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | The CCP4 study weekend is a two day workshop, the organisation of which is overseen by working group 2. The meeting contains presentations, workshop type activities, and social elements that serve to build a community. While the 2022 study weekend was online, the event in 2023 was a live event with 230 participants. |
| Year(s) Of Engagement Activity | 2022,2023 |
| URL | https://www.ccp4.ac.uk/?workshop=ccp4-study-weekend-2023 |
| Description | CCP4 study weekend |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | The CCP4 study weekend is a two day workshop, the organisation of which is overseen by working group 2. The meeting contains presentations, workshop type activities, and social elements that serve to build a community. |
| Year(s) Of Engagement Activity | 2020 |
| URL | http://www.cvent.com/events/ccp4-study-weekend-2020/event-summary-001c74f5ecfa4987af3e908c7a9d7d60.a... |
| Description | CCP4 study weekend |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | The study weekend 2021 and 2022 features novel software developments and technology and is intended as a learning platform for the crystallographic and wider scientific community. Due to the COVID impact, the workshop was converted to an online format in 2021 and in 2021. This meant that the duration of the CCP4 study weekend was four half days in 2021, rather that the two day format of previous years. The meeting was held in the afternoon to allow participation of the Americas. In 2022 the meeting ran over three days, as it was originally planned as a hybrid event, but later had to be converted to online because of high COVID numbers. The organisation and appointment of organisers is overseen by working group 2. Tews appoints the scientific organisers team on mandate of WG2. There were also various technical discussions required for conversion to the online format. The meeting contains presentations, workshop type activities, and social elements that serve to build a community. |
| Year(s) Of Engagement Activity | 2021,2022 |
| URL | https://www.ccp4.ac.uk/?workshop=ccp4-study-weekend-2022 |
| Description | South West Structural Biology Conference SWSBC (online) organiser |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Postgraduate students |
| Results and Impact | Organiser of the SWSBC meeting in 2020 and 2021. Format was online. 2020: six universities contributed chairs that helped the organisation 2021: Oversight of the organisation of the meeting, handed over to ECRs |
| Year(s) Of Engagement Activity | 2020,2021 |
| URL | https://blogs.exeter.ac.uk/swsbc2021/ |
| Description | Working Group 2 meeting |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Working group meetings take place three times per year and bring together CCP4 grant holders, CCP4 program developers, and users both from the academic communities as well as from industry. The working group steers dissemination and teaching to the community in workshops and meetings and discusses software development undertaken by CCP4 by providing a platform to report on new developments or test out novel software. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.ccp4.ac.uk/wg/ |
| Description | Working Group 2 meeting |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Working group 2 meetings took place three times in 2020 and five times in 2021. COVID had an impact as f2f meeting were no longer possible, which in turn led to meeting being shorter, but more frequent. Working group 2 meetings bring together CCP4 grant holders, CCP4 program developers, and users both from the academic communities as well as from industry. The working group steers dissemination and teaching to the community in workshops and meetings and discusses software development undertaken by CCP4 by providing a platform to report on new developments or test out novel software. Tews chairs WG2, organises and calls the meeting, and sets the agenda. |
| Year(s) Of Engagement Activity | 2020,2021 |
| URL | https://www.ccp4.ac.uk/wg/ |
| Description | Working Group 2 meeting |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Working group 2 meetings took place six times in 2022, up from five in the previous year. The structure of the meetings was changed, with alternating science and organisational meetings. All took place online. In 2023, one Working Group 2 meeting was chaired, this time as a live event in London. Working group 2 meetings bring together CCP4 grant holders, CCP4 program developers, and users both from the academic communities as well as from industry. The working group steers dissemination and teaching to the community in workshops and meetings and discusses software development undertaken by CCP4 by providing a platform to report on new developments or test out novel software. Tews chairs WG2, organises and calls the meeting, and sets the agenda. |
| Year(s) Of Engagement Activity | 2022,2023 |
| URL | https://www.ccp4.ac.uk/?page_id=188 |