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Mining of protein data bank and feedback to X-ray crystal structure solution and analysis

蛋白质数据库挖掘及X射线晶体结构解析与分析反馈

基本信息

批准号：
BB/F001134/1
负责人：
Garib Murshudov
金额：
$ 32.45万
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%2FF001134%2F1
关键词：
Mining protein data bank feedback

项目摘要

The aim is to improve the computer software used in determining the 3-D structures of complex biological molecules which make up living organisms. These molecules are coded for by a 'blueprint', in the form of a DNA sequence in the genome, which describes how to make them. Due to enormous advances in molecular biology, a number of projects, including the Human Genome Project, have led to the determination of the complete DNA sequences of a number of organisms. We can therefore read the plans for many of the molecules of life. However without knowledge of their 3-D structure, it is very hard to understand how they actually work. Understanding this is an important step in fixing them when they go wrong, and therefore, in curing a range of illnesses as well as using such molecules in a range of applications in biotechnology. The solution to this problem is through Structural Biology, in which the molecules are manufactured on the basis of their blueprints and 3-D models are constructed for them usually using X-ray crystallography. This allows pictures to be made of biological molecules in which individual atoms can be identified. Crystallography is analogous to the use of a microscope to magnify objects, which are smaller than can seen with the naked eye. However, even the optical microscope has limitations, and we cannot see objects which are smaller than the wavelength of light, roughly 1 millionth of a metre. Atoms are about 1000 times small than this, and we need to use X-rays, which have a wavelength about the same as the size of the atoms, in order to see them. Unfortunately structure solution by X-ray crystallography is complicated because unlike the optical microscope, there is no lens system for X-rays and we need to carry out a number of challenging experiments followed by complex computation and problem solving by experienced scientists. This is especially complex when we look at crystals of proteins, which are actually imperfect and contain about 50% water. The aim of this project is to improve some of the key computational tools of crystallography to make this task easier and more automatic, and to allow the solution of more difficult problems. The basic problem lies in the low observation to parameter ration in protein crystallography (equivalent to a low signal-to-noise ratio in image recognition). Advanced statistical methods are required to make the best use of the limited data available.

其目的是改进用于确定构成生物体的复杂生物分子的三维结构的计算机软件。这些分子是由基因组中DNA序列形式的“蓝图”编码的，它描述了如何制造它们。由于分子生物学的巨大进步，包括人类基因组计划在内的许多项目已经确定了许多生物体的完整DNA序列。因此，我们可以解读许多生命分子的结构。然而，如果不知道它们的3D结构，就很难理解它们实际上是如何工作的。理解这一点是在它们出错时修复它们的重要一步，因此，在治疗一系列疾病以及在生物技术的一系列应用中使用这些分子方面。这个问题的解决方案是通过结构生物学，其中分子是根据其蓝图制造的，通常使用X射线晶体学为它们构建3D模型。这使得生物分子的图片可以被识别出来。晶体学类似于使用显微镜来放大物体，这些物体比肉眼所能看到的要小。然而，即使是光学显微镜也有其局限性，我们无法看到比光波长（约为百万分之一米）更小的物体。原子比这个小1000倍，我们需要使用X射线，它的波长与原子的大小大致相同，以便看到它们。不幸的是，X射线晶体学的结构解决方案是复杂的，因为与光学显微镜不同，X射线没有透镜系统，我们需要进行一些具有挑战性的实验，然后由经验丰富的科学家进行复杂的计算和解决问题。当我们观察蛋白质晶体时，这一点尤其复杂，蛋白质晶体实际上是不完美的，含有约50%的水。该项目的目的是改进晶体学的一些关键计算工具，使这项任务更容易，更自动化，并允许解决更困难的问题。基本问题在于蛋白质晶体学中的低观测参数比（相当于图像识别中的低信噪比）。需要先进的统计方法来最好地利用现有的有限数据。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

REFMAC5 for the refinement of macromolecular crystal structures.

DOI：
10.1107/s0907444911001314
发表时间：
2011-04
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
0
作者：
Murshudov GN;Skubák P;Lebedev AA;Pannu NS;Steiner RA;Nicholls RA;Winn MD;Long F;Vagin AA
通讯作者：
Vagin AA

Structural rearrangement accompanying ligand binding in the GAF domain of CodY from Bacillus subtilis.

DOI：
10.1016/j.jmb.2009.05.077
发表时间：
2009-07-31
期刊：
JOURNAL OF MOLECULAR BIOLOGY
影响因子：
5.6
作者：
Levdikov, Vladimir M.;Blagova, Elena;Colledge, Vicki L.;Lebedev, Andrey A.;Williamson, David C.;Sonenshein, Abraham L.;Wilkinson, Anthony J.
通讯作者：
Wilkinson, Anthony J.

Structural flexibility of the macrophage dengue virus receptor CLEC5A: implications for ligand binding and signaling.

巨噬细胞登革热病毒受体 CLEC5A 的结构灵活性：对配体结合和信号传导的影响。

DOI：
10.1074/jbc.m111.226142
发表时间：
2011
期刊：
The Journal of biological chemistry
影响因子：
0
作者：
Watson AA
通讯作者：
Watson AA

Crystal structure of the FimD usher bound to its cognate FimC-FimH substrate.

DOI：
10.1038/nature10109
发表时间：
2011-06-02
期刊：
NATURE
影响因子：
64.8
作者：
Phan, Gilles;Remaut, Han;Wang, Tao;Allen, William J.;Pirker, Katharina F.;Lebedev, Andrey;Henderson, Nadine S.;Geibel, Sebastian;Volkan, Ender;Yan, Jun;Kunze, Micha B. A.;Pinkner, Jerome S.;Ford, Bradley;Kay, Christopher W. M.;Li, Huilin;Hultgren, Scott J.;Thanassi, David G.;Waksman, Gabriel
通讯作者：
Waksman, Gabriel

JLigand: a graphical tool for the CCP4 template-restraint library.