Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM): 2021 - 2026

电子冷冻显微镜协作计算项目 (CCP-EM)：2021 - 2026

• 批准号: MR/V000403/1
• 负责人: Martyn Winn
• 金额: $ 208.4万
• 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: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV000403%2F1
• 关键词: Collaborative; Computational; Project; Electron; cryo

The behaviour of living systems ultimately comes down to the interactions of biological molecules inside cells, and understanding these is vital to numerous human efforts, including controlling disease and improving food production. While experimental techniques such as macromolecular crystallography have for many years given detailed information on important molecules in the cell, many classes of molecules are not amenable to this technique. Moreover, as our understanding of pathways in the cell grows, there is increasing interest in the context in which these molecules operate. In other words, where in the cell do these molecules do their job, and which other cellular components are necessary for their function. Electron cryo-Microscopy (cryoEM) 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 internal molecular details from within intact parts of cells or tissues. Advances in instrumentation and data processing led to a significant increase in the quality of cryoEM data, which was characterised in 2014 as the "Resolution Revolution", and recognised by the 2017 Nobel Prize in Chemistry. Consequently there has been a surge in interest in the technique from structural and cellular biologists trying to understand a wide range of biological systems. There has been significant investment in the research infrastructure supporting cryoEM, most notably the establishment of several electron microscope facilities around the country. In the last few years, pharmaceutical companies and biotechnology companies have recognised the importance of cryoEM to their discovery pipelines, and have also begun investing in the area. A key component of this research infrastructure is the computational support to manage the data, process the micrographs, and interpret the data in terms of molecular volumes and/or atomic structures. The Collaborative Computational Project for Electron cryo-Microscopy (CCP-EM) was established during the period 2012 - 2016 to provide this part of the research infrastructure.The proposed project is intended to provide continued support to the cryoEM community. One of the major products of the CCP-EM partnership is a software suite for processing cryoEM data collected at microscope facilities. Individual computer programs in this suite are developed independently, either by members of CCP-EM or collaborators. The role of CCP-EM is to collate these programs into a single suite, develop workflows through the suite, and distribute the suite to practising scientists. When done well, this is a win-win arrangement in which scientists get access to a comprehensive set of software in one place, and methods developers get access to a large user base. It is well known, however, that software rapidly becomes unusable if not actively maintained and it is the responsibility of the core team of CCP-EM to ensure the longevity of software in the suite.We will also expand the scope of the suite. We will improve the tools for validating the structural information obtained, and facilitate the deposition of data in international archives. We will help to drive FAIR principles - that data from cryoEM experiments are accessible and usable to the wider community. We will increase our support for sub-tomogram averaging, a particular technique for obtaining in situ structural information of molecules. Finally, we will make more use of machine learning i.e. advanced algorithms that can learn from the data.All these advances will be tightly coupled with our on-going user training programme, and support for individual methods developers. We will also continue our very popular annual Spring Symposium, which now provides a forum for 300 researchers to share experiences and to develop the cryoEM community.

生命系统的行为最终取决于细胞内生物分子的相互作用，了解这些对于人类的许多努力至关重要，包括控制疾病和提高粮食产量。虽然大分子晶体学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，但许多类别的分子不适用于该技术。此外，随着我​​们对细胞通路的了解不断加深，人们对这些分子运作的背景也越来越感兴趣。换句话说，这些分子在细胞中的什么位置发挥作用，以及哪些其他细胞成分对其功能是必需的。冷冻电子显微镜（cryoEM）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完整部分内的内部分子细节。仪器和数据处理的进步导致冷冻电镜数据质量显着提高，这在 2014 年被称为“分辨率革命”，并获得了 2017 年诺贝尔化学奖的认可。因此，结构和细胞生物学家对这项技术的兴趣激增，试图了解广泛的生物系统。支持冷冻电镜的研究基础设施进行了大量投资，最引人注目的是在全国各地建立了多个电子显微镜设施。在过去几年中，制药公司和生物技术公司已经认识到冷冻电镜对其发现管道的重要性，并开始对该领域进行投资。该研究基础设施的一个关键组成部分是管理数据、处理显微照片以及根据分子体积和/或原子结构解释数据的计算支持。电子冷冻显微镜协作计算项目 (CCP-EM) 于 2012 年至 2016 年期间建立，旨在提供这部分研究基础设施。拟议项目旨在为冷冻电子显微镜界提供持续支持。 CCP-EM 合作伙伴关系的主要产品之一是用于处理在显微镜设施中收集的冷冻电镜数据的软件套件。该套件中的各个计算机程序是由 CCP-EM 成员或合作者独立开发的。 CCP-EM 的作用是将这些程序整理成一个套件，通过该套件开发工作流程，并将该套件分发给执业科学家。如果做得好，这是一种双赢的安排，科学家可以在一个地方访问一套全面的软件，而方法开发人员可以访问大量的用户群。然而，众所周知，如果不积极维护，软件很快就会变得无法使用，确保套件中软件的使用寿命是 CCP-EM 核心团队的责任。我们还将扩大套件的范围。我们将改进验证所获得的结构信息的工具，并促进数据在国际档案中的存放。我们将帮助推动公平原则——冷冻电镜实验的数据可供更广泛的社区访问和使用。我们将增加对亚断层图平均的支持，这是一种获取分子原位结构信息的特殊技术。最后，我们将更多地利用机器学习，即可以从数据中学习的高级算法。所有这些进步将与我们正在进行的用户培训计划以及对个别方法开发人员的支持紧密结合。我们还将继续举办非常受欢迎的年度春季研讨会，该研讨会现在为 300 名研究人员提供了一个分享经验和发展冷冻电镜社区的论坛。

项目成果

Improving sampling of crystallographic disorder in ensemble refinement.

改进系综细化中晶体无序的采样。

• DOI: http://dx.10.1107/s2059798321010044
• 发表时间: 2021
• 期刊: Acta crystallographica. Section D, Structural biology
• 作者: Ploscariu N

Real space in cryo-EM: the future is local

冷冻电镜中的真实空间：未来属于本地

• DOI: http://dx.10.1107/s2059798321012286
• 发表时间: 2022
• 期刊: Acta Crystallographica Section D Structural Biology
• 作者: Palmer C

Overview and applications of map and model validation tools in the CCP-EM software suite.

CCP-EM 软件套件中地图和模型验证工具的概述和应用。

• DOI: http://dx.10.1039/d2fd00103a
• 发表时间: 2022
• 期刊: Faraday discussions
• 影响因子: 3.4
• 作者: Joseph AP

MRC2020: improvements to Ximdisp and the MRC image-processing programs.

MRC2020：对 Ximdisp 和 MRC 图像处理程序的改进。

• DOI: http://dx.10.1107/s2052252523006309
• 发表时间: 2023
• 期刊: IUCrJ
• 影响因子: 3.9
• 作者: Short JM

Atomic model validation using the CCP-EM software suite.

使用 CCP-EM 软件套件进行原子模型验证。

• DOI: http://dx.10.1107/s205979832101278x
• 发表时间: 2022
• 期刊: Acta crystallographica. Section D, Structural biology
• 作者: Joseph AP