Towards a Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM) and bridging the gaps between structure determination methods

建立电子冷冻显微镜 (CCP-EM) 协作计算项目并弥合结构测定方法之间的差距

• 批准号: MR/J000825/1
• 负责人: Martyn Winn
• 金额: $ 77.55万
• 依托单位: Science and Technology Facilities Council
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ000825%2F1
• 关键词: Towards; Collaborative; Computational; Project; Electron

Understanding how cells work is vital to combating disease. While experimental techniques such as macromolecular crystallography and nuclear magnetic resonance spectroscopy have for many years given detailed information on important molecules in the cell, attention is now moving to how these molecules interact with each other and how they are affected by their location in the cell. Electron cryo-Microscopy (cryo-EM) provides very useful information here, and bridges the gap between individual molecules and the whole cell. In the most favourable cases, detailed images of assemblies of molecules can be obtained, while at lower resolutions electron tomograms can show slices through cells or tissues. Advances in instrumentation and data processing have led to a significant increase in the application of cryo-EM in recent years, such that it is now one of the most important experimental techniques available in structural and cellular biology.To exploit fully cryo-EM requires good software for processing the primary experimental data and for interpretating it in terms of molecular or cellular structure. However, software provision is patchy and fragmented, and individual labs face a steep learning curve when trying to create a suitable software environment for their projects. The macromolecular crystallography community faced such a challenge more than 30 years ago, and the Collaborative Computational Project No. 4 (CCP4) was created to address this challenge. In the years following, CCP4 has grown to be a major international project, and has underpinned many of the advances in our understanding of cells at the molecular level. In the last 10 years, the sister project CCPN has performed a similar role for the nuclear magnetic resonance spectroscopy community. The field of cryo-EM needs a similar initiative, and this proposal is a first step in that direction.There are at least 25 groups in the UK active in the field of cryo-EM. We are proposing a Partnership open to all UK groups with the aim of establishing a Collaborative Computational Project (CCP-EM). The CCP-EM will coordinate efforts within the UK community. It will support users through dissemination of information on available software, helpdesk support, and directed training. It will support developers through technical help and by helping to distribute their software to the community. Gaps in software provision will be identified, and where feasible new software written.The Partnership will lead to a better use of software within UK groups. It will relieve some of the burden connected with understanding and installing a wide range of incompatible software. The support of a dedicated group of scientists will greatly speed up the process of establishing new groups or helping established microscopists move into new areas (such as tomography). However, the most important output is the development of a community spirit, that encourages individual scientists to pool their efforts. The creation of scientific communities in the UK leads to the best use of public money, and maximises the return on the UK's investment in microscopy facilities.

了解细胞如何工作对对抗疾病至关重要。虽然实验技术，如大分子晶体学和核磁共振光谱学多年来已经给出了细胞中重要分子的详细信息，但现在注意力正在转移到这些分子如何相互作用以及它们在细胞中的位置如何影响它们。冷冻电子显微镜（cryo-EM）提供了非常有用的信息，并在单个分子和整个细胞之间架起了差距的桥梁。在最有利的情况下，可以获得分子组装的详细图像，而在较低分辨率下，电子断层摄影可以显示细胞或组织的切片。近年来，由于仪器和数据处理技术的进步，冷冻电镜的应用显著增加，使其成为结构和细胞生物学中最重要的实验技术之一，充分利用冷冻电镜需要良好的软件来处理原始实验数据，并根据分子或细胞结构对其进行解释。然而，软件供应是不完整和分散的，并且当尝试为其项目创建合适的软件环境时，单个实验室面临着陡峭的学习曲线。大分子晶体学界在30多年前就面临着这样的挑战，为了应对这一挑战，创建了第4号合作计算项目（CCP4）。在接下来的几年里，CCP4已经发展成为一个重要的国际项目，并支持了我们在分子水平上理解细胞的许多进展。在过去的10年里，姐妹项目CCPN在核磁共振光谱学领域发挥了类似的作用。冷冻电镜领域需要一个类似的倡议，这个建议是朝着这个方向迈出的第一步。在英国，至少有25个团体活跃在冷冻电镜领域。我们提议建立一个对所有英国团体开放的伙伴关系，目的是建立一个合作计算项目（CCP-EM）。CCP-EM将协调英国社区内部的努力。它将通过传播关于现有软件的信息、服务台支助和有针对性的培训来支助用户。它将通过技术帮助和帮助向社区分发软件来支持开发人员。将确定软件供应方面的差距，并在可行的情况下编写新的软件。它将减轻一些与理解和安装各种不兼容软件有关的负担。一个专门的科学家小组的支持将大大加快建立新小组的过程，或帮助建立显微镜进入新的领域（如断层扫描）。然而，最重要的成果是发展了一种社区精神，鼓励科学家个人共同努力。在联合王国建立科学社区，使公共资金得到最佳利用，并使联合王国在显微镜设施方面的投资回报最大化。

项目成果

Refinement of atomic models in high resolution EM reconstructions using Flex-EM and local assessment.

• DOI: 10.1016/j.ymeth.2016.03.007
• 发表时间: 2016-05-01
• 期刊: Methods (San Diego, Calif.)
• 作者: Joseph AP;Malhotra S;Burnley T;Wood C;Clare DK;Winn M;Topf M
• 通讯作者: Topf M

MRC2014: Extensions to the MRC format header for electron cryo-microscopy and tomography.

• DOI: 10.1016/j.jsb.2015.04.002
• 发表时间: 2015-11
• 期刊: Journal of structural biology
• 影响因子: 3
• 作者: Cheng A;Henderson R;Mastronarde D;Ludtke SJ;Schoenmakers RH;Short J;Marabini R;Dallakyan S;Agard D;Winn M
• 通讯作者: Winn M

Recent developments in the CCP-EM software suite.

• DOI: 10.1107/s2059798317007859
• 发表时间: 2017-06-01
• 期刊: Acta crystallographica. Section D, Structural biology
• 作者: Burnley T;Palmer CM;Winn M
• 通讯作者: Winn M

Automating tasks in protein structure determination with the clipper python module.

• DOI: 10.1002/pro.3299
• 发表时间: 2018-01
• 期刊: Protein science : a publication of the Protein Society
• 作者: McNicholas S;Croll T;Burnley T;Palmer CM;Hoh SW;Jenkins HT;Dodson E;Cowtan K;Agirre J
• 通讯作者: Agirre J

Collaborative computational project for electron cryo-microscopy.

• DOI: 10.1107/s1399004714018070
• 发表时间: 2015-01-01
• 期刊: Acta crystallographica. Section D, Biological crystallography
• 作者: Wood C;Burnley T;Patwardhan A;Scheres S;Topf M;Roseman A;Winn M
• 通讯作者: Winn M