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

了解细胞是如何工作的，对于抗击疾病至关重要。虽然多年来，大分子结晶学和核磁共振光谱等实验技术一直提供了关于细胞中重要分子的详细信息，但现在人们的注意力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上。电子冷冻显微镜(Cryo-EM)在这里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一座桥梁。在最有利的情况下，可以获得分子组装的详细图像，而在分辨率较低的情况下，电子断层图像可以显示穿过细胞或组织的切片。近年来，随着仪器和数据处理技术的进步，低温电子显微镜的应用越来越广泛，已成为结构生物学和细胞生物学中最重要的实验技术之一。要充分利用低温电子显微镜，需要有良好的软件来处理原始实验数据，并从分子或细胞结构的角度对其进行解释。然而，软件的提供是零散和零散的，个别实验室在试图为其项目创建合适的软件环境时面临着陡峭的学习曲线。大分子结晶界在30多年前就面临着这样的挑战，而协作计算第四号项目(CCP4)就是为了应对这一挑战而创建的。在接下来的几年里，CCP4已经成长为一个重要的国际项目，并在分子水平上支持了我们对细胞理解的许多进展。在过去10年中，姊妹项目CCPN为核磁共振波谱学社区发挥了类似的作用。低温EM领域需要类似的倡议，这项提议是朝着这个方向迈出的第一步。英国至少有25个组织活跃在低温EM领域。我们提议建立一个对所有英国团体开放的合作伙伴关系，目的是建立一个合作计算项目(CCP-EM)。CCP-EM将协调英国社区内的努力。它将通过传播有关现有软件、服务台支持和定向培训的信息来支持用户。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。将找出软件供应方面的差距，并在可行的情况下编写新的软件。这一伙伴关系将导致英国集团更好地使用软件。它将减轻一些与理解和安装各种不兼容软件相关的负担。一群敬业的科学家的支持将大大加快建立新团队或帮助老牌显微镜专家进入新领域(如断层摄影术)的进程。然而，最重要的成果是发展了一种社区精神，这种精神鼓励个人科学家共同努力。在英国创建科学社区将使公共资金得到最佳利用，并使英国在显微镜设施上的投资回报最大化。

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.