CCP4: Low resolution complexes handling difficult data; empowering structural biologists and supporting UK structural biology

CCP4：处理困难数据的低分辨率复合体；

• 批准号: BB/F020805/1
• 负责人: Martyn Winn
• 金额: $ 159.17万
• 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: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF020805%2F1
• 关键词: CCP4; Low; resolution; complexes; handling

Structural Biology is a powerful tool for analysing biological molecules. In essence it locates the atoms that make up proteins and other biomolecules. It is used in basic science to define the 3D structures of such molecules as the ribosome, ion channels and complex protein assemblies such as ATPase. Once a 3D 'model' of all the atoms in the biological model is available, it is possible to make deductions about how the molecule functions within the organism. This knowledge has corresponding applications in controlling that function, often leading to medical advances in drug design, better understanding of biological and feedback systems in the natural environment, new approaches in chemical engineering, and many other benefits. The process of 'solving' the structure involves first obtaining crystals and then exposing these to X-rays: this is equivalent to using a very powerful microscope and allows us to 'see' individual atoms. Getting crystals is in itself very demanding and involves a lot of skill and scientific insight. There is an additional problem in using X-rays in that there is no lens system for the microscope. This means that indirect, so-called diffraction images of the crystal are recorded. The process of extracting data from these images and proceeding to a final structure is computationally intensive and requires an entirely different set of skills from those of the biologist. Developing new computer methods and crucially embedding them in robust easy-to-use software will transform structural biology from a labour intensive highly technical process to a routine tool in biology. The main focus of this grant is on the computational process of solving 3D structures. CCP4 is a project which has collected, developed, packaged and distributed software for the many stages of this process, acting as a focus for methods development for over 25 years and making software available to both Academic and Industrial teams working in this area. It is an excellent example of technology transfer of basic science into a major UK Industry: Pharmaceutical development. The problem cannot yet be said to be totally solved. Biologists firstly are tackling more and more difficult structures, which require novel techniques. In addition, they are solving large number of sometimes related structures, such as a series of mutants and complexes, where automated high throughput is vital and systematic record keeping is essential. This proposal is focussed on enabling these developments.

结构生物学是分析生物分子的强大工具。本质上，它定位构成蛋白质和其他生物分子的原子。它在基础科学中用于定义核糖体、离子通道和复杂蛋白质组装体（例如 ATP 酶）等分子的 3D 结构。一旦生物模型中所有原子的 3D“模型”可用，就可以推断分子在生物体内的功能。这些知识在控制该功能方面具有相应的应用，通常会带来药物设计方面的医学进步、对自然环境中的生物和反馈系统的更好理解、化学工程的新方法以及许多其他好处。 “解析”结构的过程首先需要获得晶体，然后将它们暴露在 X 射线下：这相当于使用非常强大的显微镜，使我们能够“看到”单个原子。获得晶体本身要求非常高，需要大量的技能和科学洞察力。使用 X 射线还有一个额外的问题，因为显微镜没有透镜系统。这意味着记录了晶体的间接所谓的衍射图像。从这些图像中提取数据并形成最终结构的过程需要大量计算，并且需要与生物学家完全不同的技能。开发新的计算机方法并将其嵌入到强大且易于使用的软件中将把结构生物学从劳动密集型的高技术过程转变为生物学的常规工具。该资助的主要重点是解决 3D 结构的计算过程。 CCP4 是一个为该过程的多个阶段收集、开发、打包和分发软件的项目，25 年来一直是方法开发的焦点，并向该领域的学术和工业团队提供软件。这是将基础科学技术转移到英国主要行业：制药开发的一个很好的例子。问题还不能说已经完全解决。生物学家首先正在解决越来越困难的结构，这需要新技术。此外，他们正在解决大量有时相关的结构，例如一系列突变体和复合物，其中自动化高通量至关重要，系统记录保存也至关重要。该提案的重点是促进这些发展。

项目成果

REFMAC5 for the refinement of macromolecular crystal structures.

REFMAC5 用于细化大分子晶体结构。

• DOI: http://dx.10.1107/s0907444911001314
• 发表时间: 2011
• 期刊: Acta crystallographica. Section D, Biological crystallography
• 作者: Murshudov GN

Structure of the 2,4'-dihydroxyacetophenone dioxygenase from Alcaligenes sp. 4HAP.

产碱菌属 2,4-二羟基苯乙酮双加氧酶的结构。

• DOI: http://dx.10.1107/s1399004714015053
• 发表时间: 2014
• 期刊: Acta crystallographica. Section D, Biological crystallography
• 作者: Keegan R

Enhanced fold recognition using efficient short fragment clustering.

使用高效的短片段聚类增强折叠识别。

• 发表时间: 2012-06-16
• 期刊: Journal of molecular biochemistry
• 作者: E. Krissinel

Recent developments in MrBUMP : better search-model preparation, graphical interaction with search models, and solution improvement and assessment

MrBUMP 的最新发展：更好的搜索模型准备、与搜索模型的图形交互以及解决方案改进和评估

• DOI: http://dx.10.1107/s2059798318003455
• 发表时间: 2018
• 期刊: Acta Crystallographica Section D Structural Biology
• 作者: Keegan R

CCP4i2: the new graphical user interface to the CCP4 program suite.

CCP4i2：CCP4 程序套件的新图形用户界面。

• DOI: http://dx.10.1107/s2059798317016035
• 发表时间: 2018
• 期刊: Acta crystallographica. Section D, Structural biology
• 作者: Potterton L