The Dundee Resource for Protein Structure Prediction and Sequence Analysis

邓迪蛋白质结构预测和序列分析资源

• 批准号: BB/J019364/1
• 负责人: Geoffrey Barton
• 金额: $ 80.77万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FJ019364%2F1
• 关键词: Dundee; Resource; Protein; Structure; Prediction

This resource application is focused on supporting and maintaining computer tools and techniques developed at the University of Dundee that are in daily use by thousands of biological scientists throughout the UK and the world. The resource will not only ensure that these tools are readily available to all scientists, but also improve the ability of scientists and students to use them through better interfaces and via regular face-to-face training courses and other on-line materials. The tools focus on the analysis of protein sequences and structures which are briefly introduced here. The plans to make a plant, animal or micro-organism are encoded as the molecule DNA and known as its genome. The genome can be represented as a long word made up of four different letters (A, C, G, T). The genome may be a few thousand letters long for a virus, to several billion letters for plants and animals. The genome is divided up into regions called genes which are translated by complex molecular machines into other molecules such as proteins. Humans and other animals have 20-30,000 genes that code for proteins and each protein made up of a sequence of 20 different amino acid types joined together in a chain. Protein sequences from an organism vary in length from a few amino acids, to several thousand and can be represented as a word made up of 20 different letter types. The protein chain folds up into a complex three-dimensional shape that is defined primarily by its sequence. The shape of the protein, its "conformation", dictates the biological function of the protein, so understanding the conformation of a protein is vitally important to understanding the protein function. Over recent years there have been huge advances in technology to sequence DNA and so the genomes of many different organisms have been determined. As a consequence, the sequences of several million proteins are now known but less than 100,000 have had their detailed three-dimensional structures worked out. The computational tools that will make up this resource help to bridge this information gap by classifying protein sequences and making predictions of protein structure that can guide biologists to design more efficient and effective experiments. The main objectives of the proposal are to provide support, maintenance and training for the popular JPred protein structure prediction server which performs up to 95,000 predictions monthly for scientists in 140 countries, the TarO protein sequence analysis suite and Kinomer protein kinase classifier and database. The new resource will integrate these individual tools with a consistent look-and-feel and make them available to researchers and tool developers in new ways over and above a conventional web site. Web sites are good for humans to interact with, but less useful for computer software to interface to. Since our tools are useful for large analyses that might be done on many thousands of proteins, the new resource will also support a novel "web services" interface to the tools. Web services allow a program or application to be run remotely from within a program. For example, I might have a program running on my desktop computer, but call for an intensive calculation to be done on a remote high-performance computer system. We have recently developed a new method to deploy web services (called JABAWS) that makes installation of web services straightforward. A key part of the new resource will be to add more complex applications such as structure prediction to Jabaws and so make them readily available to programmers and end-users

该资源应用程序的重点是支持和维护邓迪大学开发的计算机工具和技术，英国和世界各地数千名生物科学家每天都在使用这些工具和技术。该资源不仅将确保所有科学家都能轻松使用这些工具，而且还将通过更好的界面以及定期的面对面培训课程和其他在线材料，提高科学家和学生使用这些工具的能力。这些工具侧重于蛋白质序列和结构的分析，这里简要介绍一下。制造植物、动物或微生物的计划被编码为 DNA 分子，并被称为基因组。基因组可以表示为由四个不同字母（A、C、G、T）组成的长单词。对于病毒来说，基因组可能有几千个字母，对于植物和动物来说，基因组可能有数十亿个字母。基因组被划分为称为基因的区域，这些区域被复杂的分子机器翻译成其他分子，例如蛋白质。人类和其他动物有 20-30,000 个编码蛋白质的基因，每种蛋白质都由 20 种不同氨基酸类型的序列组成，这些氨基酸类型连接在一起。生物体的蛋白质序列长度各异，从几个氨基酸到几千个氨基酸不等，可以表示为由 20 种不同字母类型组成的单词。蛋白质链折叠成复杂的三维形状，该形状主要由其序列定义。蛋白质的形状，即它的“构象”，决定了蛋白质的生物学功能，因此了解蛋白质的构象对于理解蛋白质的功能至关重要。近年来，DNA 测序技术取得了巨大进步，因此许多不同生物体的基因组已被确定。因此，现在已经知道了数百万种蛋白质的序列，但只有不到 100,000 个蛋白质的详细三维结构得到了解决。构成该资源的计算工具通过对蛋白质序列进行分类并预测蛋白质结构来帮助弥合这一信息差距，从而指导生物学家设计更高效和有效的实验。该提案的主要目标是为流行的 JPred 蛋白质结构预测服务器、TarO 蛋白质序列分析套件以及 Kinomer 蛋白激酶分类器和数据库提供支持、维护和培训，该服务器每月为 140 个国家的科学家执行多达 95,000 次预测。新资源将以一致的外观和感觉整合这些单独的工具，并以超越传统网站的新方式提供给研究人员和工具开发人员。网站有利于人类交互，但对于计算机软件的交互却不太有用。由于我们的工具可用于对数千种蛋白质进行的大型分析，因此新资源还将支持工具的新颖“网络服务”界面。 Web 服务允许程序或应用程序在程序内远程运行。例如，我可能有一个程序在我的台式计算机上运行，​​但需要在远程高性能计算机系统上完成密集计算。我们最近开发了一种部署 Web 服务的新方法（称为 JABAWS），使 Web 服务的安装变得简单。新资源的一个关键部分将是向 Jabaws 添加更复杂的应用程序（例如结构预测），以便程序员和最终用户可以轻松使用它们

项目成果

Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics.

• DOI: 10.7554/elife.70658
• 发表时间: 2021-08-26
• 期刊: eLife
• 影响因子: 7.7
• 作者: Barton MI;MacGowan SA;Kutuzov MA;Dushek O;Barton GJ;van der Merwe PA
• 通讯作者: van der Merwe PA

Effects of common mutations in the SARS-CoV-2 Spike RBD domain and its ligand the human ACE2 receptor on binding affinity and kinetics

• DOI: 10.1101/2021.05.18.444646
• 发表时间: 2021-05
• 期刊: bioRxiv
• 作者: Michael I. MacGowan;Stuart Kutuzov;Mikhail Dushek;O. Barton;Geoffrey J. Merwe;P. Anton;Michael I. Barton;Stuart A. MacGowan;M. Kutuzov;Omer Dushek;G. Barton;A. V. D. Merwe

Phosphoproteomic screening identifies Rab GTPases as novel downstream targets of PINK1.

• DOI: 10.15252/embj.201591593
• 发表时间: 2015-11-12
• 期刊: The EMBO journal
• 作者: Lai YC;Kondapalli C;Lehneck R;Procter JB;Dill BD;Woodroof HI;Gourlay R;Peggie M;Macartney TJ;Corti O;Corvol JC;Campbell DG;Itzen A;Trost M;Muqit MM
• 通讯作者: Muqit MM