Tool for Predicting Glycosaminoglycan Recognition of Proteins

预测蛋白质糖胺聚糖识别的工具

• 批准号: 10411438
• 负责人: Umesh Ramanlal Desai
• 金额: $ 6.88万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-03 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10411438
• 关键词: Address; Affinity; Algorithms; Amino Acid Sequence; Antithrombins; Binding; Binding Proteins; Biochemical; Biological; CXCL13 gene; Chondroitin Sulfates; Coagulation Process; Communities; Computer Analysis; Dermatan Sulfate; Development; EP300 gene; FGF1 gene; FGFR1 gene; Focus Groups; Generations; Glycobiology; Glycosaminoglycans; Growth; Heparin; Heparin Cofactor II; Heparitin Sulfate; Human; Individual; Inflammation; Ireland; Knowledge; Lead; Leukocyte Elastase; Libraries; Morphogenesis; Nature; Oligonucleotides; Oligosaccharides; Outcome; Output; Polysaccharides; Proteins; Publications; Research; Research Personnel; Role; Site; Specialist; Specificity; Structure; System; Technology; Thrombin; Time; Transforming Growth Factors; Work; biophysical techniques; cationic antimicrobial protein CAP 37; chemokine; computer code; computerized tools; dermatan sulfate chondroitin sulfate; design; experience; graphical user interface; in silico; innovation; interest; milligram; multiple myeloma M Protein; operation; predictive tools; receptor; software development; tool; user-friendly; web server; web-enabled

PROJECT SUMMARY GAGs present considerable structural diversity, which has made the study of individual GAG sequences humanly impossible. Most studies performed to date rely on heterogeneous GAG compositions, such as heparin and chondroitin sulfate. Few dozen GAG oligosaccharides have become commercially available in recent times (Sigma (US), Dextra (UK), and Iduron (UK)). Yet, purchasing even a small, reasonably diverse library of these oligosaccharides is very expensive (~$200–300 for few µg to mg each). More importantly, the oligosaccharides available from these companies are generally the common sequences and do not represent the diversity present in nature. Synthesis of GAG oligosaccharides is challenging and only a handful of groups have experience with synthesis technology. We have developed a computational tool that helps predict key GAG sequence that recognize protein with high affinity. Our tool has been validated for proteins including antithrombin, fibroblast growth factor-1 & its receptor (FGF-1/FGFR1), transforming growth factor 2 (TGF2), thrombin, histone acetyltransferase p300, human neutrophil elastase and chemokine CXCL13. We propose to make this tool freely available to the research community so that many groups can computationally assess whether their protein of interest binds GAGs. Our two aims include 1) develop a graphical user interface (GUI) on a web-server to enable researchers utilize our computational tool for studying GAG–protein interactions; and 2) advance the computational tool for predicting the interaction of commercially available GAG sequences (HP/HS and CS/DS) with proteins. These two aims directly address the RFA by making our in-house tool “significantly more straightforward and accessible for non-specialists”. In terms of output, this work will put forward a web- enabled tool carrying libraries of GAG sequences and appropriate algorithms for use by researchers from remote sites. It will add to the continuing democratization of glycan tools to enable more effective glycan research. In terms of knowledge contribution, our computational tool would help enhance understanding on how GAGs are recognized by proteins, especially those belonging to coagulation, inflammation and growth/morphogenesis systems.

项目摘要 插科打s提出了考虑结构多样性，这使得对单个插科打序列进行了研究 人类不可能。到目前 和硫酸软骨素。近来，很少有十几种寡糖在商业上获得 （Sigma（美国），Dextra（英国）和Iduron（英国））。但是，即使购买了一个小的，相当多的图书馆 寡糖非常昂贵（几毫克至Mg $ 200–300）。更重要的是，寡糖 从这些公司获得的通常是常见的序列，并不代表目前的多样性 本质。 GAG寡糖的合成具有挑战性，只有少数小组有经验 合成技术。我们已经开发了一种计算工具，可以帮助预测关键的堵嘴序列 识别具有高亲和力的蛋白质。我们的工具已被验证用于包括抗凝血酶，成纤维细胞在内的蛋白质 生长因子1及其受体（FGF-1/FGFR1），转化生长因子2（TGF2），凝血酶，组蛋白 乙酰转移酶P300，人嗜中性粒细胞弹性酶和趋化因子CXCL13。我们建议自由制作此工具 研究界可用，以便许多群体可以计算评估其蛋白质是否蛋白质 兴趣约束插科打。我们的两个目标包括1）在网络服务器上开发图形用户界面（GUI） 使研究人员能够利用我们的计算工具来研究GAG - 蛋白质相互作用； 2）进步 用于预测市售GAG序列（HP/HS）相互作用的计算工具 和蛋白质的CS/DS）。这两个目标通过使我们的内部工具直接解决了RFA 对于非专家们而言，更简单，可以访问”。就输出而言，这项工作将提出一个网络 启用了携带插科打序列的库和适当算法的工具，可用于远程研究人员 站点。这将增加聚糖工具的持续民主化，以实现更有效的聚糖研究。在 知识贡献条款，我们的计算工具将有助于增强对插科打o的方式的理解 被蛋白质识别，尤其是属于凝血，炎症和生长/形态发生的蛋白质 系统。