A pipeline to translate glycosaminoglycan sequences into 3D models. Application to the exploration of glycosaminoglycan conformational space
A pipeline to translate glycosaminoglycan sequences into 3D models. Application to the exploration of glycosaminoglycan conformational space
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DOI：
10.1093/glycob/cwy084
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发表时间：
2019-01-01
期刊：
影响因子：
4.3
通讯作者：
Ricard-Blum, Sylvie
中科院分区：
文献类型：
--
作者：
Clerc, Olivier;Mariethoz, Julien;Ricard-Blum, Sylvie
哺乳动物糖胺多糖是由硫酸肝素、肝素、硫酸皮肤素、硫酸软骨素、硫酸角蛋白和透明质酸组成的线性复合多糖。它们与许多蛋白质结合，这些相互作用调节它们的生物活性。文献中报道的Gag-蛋白质相互作用数据大多保存在MatrixDB(http://matrixdb.univ-lyon1.fr/).)数据库中然而，缺乏一个标准的命名和机器可读的GAG格式，以及用于挖掘这些相互作用数据的生物信息学工具。我们在这里报告了自动化管道的建立，以(I)标准化与手动从文献中挑选的蛋白质相互作用的GAG序列的格式，(Ii)将它们翻译成机器可读的GlycoCT格式和SNFG(多糖的符号命名)图像，以及(Iii)将它们的序列转换成由构建器处理的格式，该构象基于由从结晶的GAG-蛋白质复合体提取的数据实验验证的构象库来产生多糖的三维结构。为此，我们开发了一个转换器(CT23D转换器)，将GAG序列的GlycoCT代码自动转换为构建三维模型所需的输入文件。
Mammalian glycosaminoglycans are linear complex polysaccharides comprising heparan sulfate, heparin, dermatan sulfate, chondroitin sulfate, keratan sulfate and hyaluronic acid. They bind to numerous proteins and these interactions mediate their biological activities. GAG-protein interaction data reported in the literature are curated mostly in MatrixDB database (http://matrixdb.univ-lyon1.fr/). However, a standard nomenclature and a machine-readable format of GAGs together with bioinformatics tools for mining these interaction data are lacking. We report here the building of an automated pipeline to (i) standardize the format of GAG sequences interacting with proteins manually curated from the literature, (ii) translate them into the machine-readable GlycoCT format and into SNFG (Symbol Nomenclature For Glycan) images and (iii) convert their sequences into a format processed by a builder generating three-dimensional structures of polysaccharides based on a repertoire of conformations experimentally validated by data extracted from crystallized GAG-protein complexes. We have developed for this purpose a converter (the CT23D converter) to automatically translate the GlycoCT code of a GAG sequence into the input file required to construct a three-dimensional model.