Tool for Predicting Glycosaminoglycan Recognition of Proteins

预测蛋白质糖胺聚糖识别的工具

• 批准号: 10062163
• 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/10062163
• 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.

项目总结