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

CCP4：低分辨率复合物；

• 批准号: BB/F020368/1
• 负责人: Keith Wilson
• 金额: $ 67.18万
• 依托单位: University of York
• 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%2FF020368%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有力工具。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诸如核糖体、离子通道和复杂蛋白质组件（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。这些知识在控制这种功能方面有相应的应用，通常导致药物设计的医学进步，更好地理解自然环境中的生物和反馈系统，化学工程的新方法以及许多其他好处。“解决”结构的过程包括首先获得晶体，然后将其暴露于X射线：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。获得水晶本身就要求很高，需要很多技能和科学见解。使用X射线还有一个问题，即显微镜没有透镜系统。这意味着间接地记录晶体的所谓衍射图像。从这些图像中提取数据并进行最终结构的过程是计算密集型的，需要与生物学家完全不同的技能。开发新的计算机方法，并将其嵌入强大的易于使用的软件中，这将使结构生物学从劳动密集型的高技术过程转变为生物学中的常规工具。该补助金的主要重点是解决3D结构的计算过程。CCP4是一个收集、开发、打包和分发这一过程的许多阶段的软件的项目，作为方法开发的重点超过25年，并为在这一领域工作的学术和工业团队提供软件。这是基础科学技术转移到英国主要产业的一个很好的例子：制药开发。这个问题还不能说已经完全解决。首先，生物学家正在解决越来越多的困难结构，这需要新的技术。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，系统记录保存至关重要。该提案的重点是促进这些发展。

项目成果

Completion of autobuilt protein models using a database of protein fragments.

• DOI: 10.1107/s0907444911039655
• 发表时间: 2012-04
• 期刊: Acta crystallographica. Section D, Biological crystallography
• 作者: Cowtan K

Features and development of Coot.

• DOI: 10.1107/s0907444910007493
• 发表时间: 2010-04
• 期刊: Acta crystallographica. Section D, Biological crystallography
• 作者: Emsley P;Lohkamp B;Scott WG;Cowtan K
• 通讯作者: Cowtan K

CCP4i2 for Programmers

面向程序员的 CCP4i2

• 发表时间: 2012
• 作者: Potterton, L

Automated nucleic acid chain tracing in real time.

自动核酸链实时追踪。

• DOI: 10.1107/s2052252514019290
• 发表时间: 2014-11-01
• 期刊: IUCrJ
• 影响因子: 3.9
• 作者: Cowtan K

Overview of the CCP4 suite and current developments.

• DOI: 10.1107/s0907444910045749
• 发表时间: 2011-04
• 期刊: Acta crystallographica. Section D, Biological crystallography
• 作者: Winn MD;Ballard CC;Cowtan KD;Dodson EJ;Emsley P;Evans PR;Keegan RM;Krissinel EB;Leslie AG;McCoy A;McNicholas SJ;Murshudov GN;Pannu NS;Potterton EA;Powell HR;Read RJ;Vagin A;Wilson KS
• 通讯作者: Wilson KS