Identification and Analysis of Natural Building Blocks for Evolution-Guided Fragment-Based Protein Design
Identification and Analysis of Natural Building Blocks for Evolution-Guided Fragment-Based Protein Design
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DOI：
10.1016/j.jmb.2020.04.013
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发表时间：
2020-06-12
影响因子：
5.6
通讯作者：
Hoecker, Birte
中科院分区：
文献类型：
--
作者：
Ferruz, Noelia;Lobos, Francisco;Hoecker, Birte
自然进化已经产生了一个令人印象深刻的多样性蛋白质宇宙通过复制和重组从一组蛋白质片段，作为积木。应用这些概念设计新的蛋白质，使用来自不同折叠的亚结构域大小的片段已被证明是实验上成功的。为了更好地理解进化如何塑造我们的蛋白质宇宙，我们对代表所有天然存在的折叠的蛋白质结构域进行了全面的比较，并确定了保守的同源蛋白质片段。通过相似性网络分析，我们总共发现了1000多个不同折叠长度的蛋白质片段。这些片段存在于非常不同的蛋白质环境中，代表了蛋白质设计的通用构建模块。这些数据可在我们的Web服务器F（old P）uzzle（fuzzle.uni-bayreuth.de）中获得，该服务器允许单独过滤数据集并为感兴趣的褶皱创建定制的网络。我们相信，我们的研究结果是结构和进化生物学家的宝贵资源，也是设计定制蛋白质的原材料。(C)2020作者（S）爱思唯尔有限公司出版
Natural evolution has generated an impressively diverse protein universe via duplication and recombination from a set of protein fragments that served as building blocks. The application of these concepts to the design of new proteins using subdomain-sized fragments from different folds has proven to be experimentally successful. To better understand how evolution has shaped our protein universe, we performed an all-against-all comparison of protein domains representing all naturally existing folds and identified conserved homologous protein fragments. Overall, we found more than 1000 protein fragments of various lengths among different folds through similarity network analysis. These fragments are present in very different protein environments and represent versatile building blocks for protein design. These data are available in our web server called F(old P)uzzle (fuzzle.uni-bayreuth.de), which allows to individually filter the dataset and create customized networks for folds of interest. We believe that our results serve as an invaluable resource for structural and evolutionary biologists and as raw material for the design of custom-made proteins. (C) 2020 The Author(s). Published by Elsevier Ltd.