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于对抗疾病至关重要。虽然大分子晶体学和核磁共振波谱等实验技术多年来已经提供了细胞中重要分子的详细信息，但现在人们的注意力转向这些分子如何相互作用以及它们在细胞中的位置如何受到影响。冷冻电子显微镜（cryo-EM）在这里提供了非常有用的信息，并弥合了单个分子和整个细胞之间的差距。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，电子断层扫描可以显示细胞或组织的切片。近年来，仪器和数据处理的进步导致冷冻电镜的应用显着增加，使其成为结构和细胞生物学中最重要的实验技术之一。要充分利用冷冻电镜，需要良好的条件用于处理主要实验数据并根据分子或细胞结构对其进行解释的软件。然而，软件供应是零散且分散的，各个实验室在尝试为其项目创建合适的软件环境时面临着陡峭的学习曲线。 30多年前，高分子晶体学界就面临着这样的挑战，协作计算项目4号（CCP4）就是为了应对这一挑战而创建的。在接下来的几年里，CCP4 已发展成为一个重要的国际项目，并支撑了我们在分子水平上理解细胞的许多进展。在过去 10 年中，姊妹项目 CCPN 为核磁共振波谱学界发挥了类似的作用。冷冻电镜领域需要类似的举措，而这项提案是朝这个方向迈出的第一步。英国至少有 25 个团体活跃在冷冻电镜领域。我们提议向所有英国团体开放合作伙伴关系，旨在建立协作计算项目（CCP-EM）。 CCP-EM 将协调英国社区内部的努力。它将通过传播有关可用软件、帮助台支持和定向培训的信息来为用户提供支持。它将通过技术帮助和帮助向社区分发他们的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软件。该合作伙伴关系将导致英国集团内部更好地使用软件。它将减轻一些与理解和安装各种不兼容软件相关的负担。专门的科学家小组的支持将大大加快建立新小组或帮助现有显微镜专家进入新领域（例如断层扫描）的过程。然而，最重要的成果是社区精神的发展，鼓励个体科学家共同努力。英国科学界的创建可以充分利用公共资金，并最大限度地提高英国在显微镜设施上的投资回报。

项目成果

Collaborative computational project for electron cryo-microscopy.

电子冷冻显微镜协作计算项目。

• DOI: http://dx.10.1107/s1399004714018070
• 发表时间: 2015
• 期刊: Acta crystallographica. Section D, Biological crystallography
• 作者: Wood C

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

使用 Flex-EM 和局部评估在高分辨率 EM 重建中细化原子模型。

• DOI: http://dx.10.1016/j.ymeth.2016.03.007
• 发表时间: 2016
• 期刊: Methods (San Diego, Calif.)
• 作者: Joseph AP

?-TEMPy: Simultaneous Fitting of Components in 3D-EM Maps of Their Assembly Using a Genetic Algorithm.

?-TEMPy：使用遗传算法在其组装的 3D-EM 图中同时拟合组件。

• DOI: http://dx.10.1016/j.str.2015.10.013
• 发表时间: 2015
• 期刊: 1993)
• 作者: Pandurangan AP

Data management challenges in three-dimensional EM.

三维 EM 中的数据管理挑战。

• DOI: http://dx.10.1038/nsmb.2426
• 发表时间: 2012
• 期刊: Nature structural & molecular biology
• 影响因子: 16.8
• 作者: Patwardhan A

Recent developments in the CCP-EM software suite.

CCP-EM 软件套件的最新发展。

• DOI: http://dx.10.1107/s2059798317007859
• 发表时间: 2017
• 期刊: Acta crystallographica. Section D, Structural biology
• 作者: Burnley T