Glycomutagenesis Tools for Structure-Based Prediction and Design of Glycosyl Transfer
用于基于结构的糖基转移预测和设计的糖突变工具
基本信息
- 批准号:9897664
- 负责人:
- 金额:$ 24.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-08-01 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAnabolismBiologicalBiologyComputational algorithmCustomDiseaseEmerging TechnologiesEnzymesGlycobiologyGlycoconjugatesGlycoproteinsGoalsKnowledgeLifeMethodsModelingMolecular ConformationOligosaccharidesPancreatic ribonucleasePolysaccharidesProteinsResearchRoleSamplingScanningSchemeScientistSignal TransductionSiteSpeedStructureTechnologyTestingTherapeuticTimeVaccinesVariantWorkbasecomputerized toolscostdesignexperimental studyglycosylationinsightnovelprotein foldingstem cell fatethree dimensional structuretool
项目摘要
Technologies to Predict and Probe Glycosyl Transfer
PROJECT SUMMARY
Glycosylation is fundamental to all life. Glycans add an additional layer of information to biomolecules, affect
both conformation and dynamics, have diverse modulatory roles, such as stabilizing protein folds and signaling
stem-cell fate, and feature prominently in disease. As our knowledge of glycosylation's mechanistic role
continues to grow, so do the opportunities for therapeutic exploitation. Emerging technologies have opened the
door to facile, scalable biosynthesis of defined glycoconjugates whose glycan moieties can be tailored for
different applications. At the same time, a set of tools has emerged to predict the 3D structures of biomolecules
rapidly and accurately and to design new biomolecules and variants. Structure prediction and design tools have
the potential to transform glycobiology by providing structural insights into the effects of glycans and additionally
by enabling design of altered and novel glycoconjugates to create new functions.
Our overarching goal is to develop complementary computational and experimental methods to probe the
structural and environmental contexts that affect glycosylation and elongation. Our research will address the
technical barriers needed to achieve these tools, namely developing methods to sample and score diverse
glycoconjugate structures and to scan alternate glycoforms in experiment. Our work will create computational
algorithms to predict glycosylation sites and elongation products and experimental tools to probe protein-wide
glycoforms in specific targets. A computational tool to design and predict favorable candidates for
experimentation would reduce costs and speed the advance of glycoscience. Experimental approaches to
synthesize diverse glycoforms will enable functional testing of alternate glycoforms.
To develop our technologies, we will computationally predict and experimentally generate constructs with
oligosaccharyl transfer to all possible sites in the Im7 and RNase A model proteins. We will then proceed to
computationally predict and experimentally test alternate elongation schemes, which result in different glycan
structures, for these constructs. Together, our tool set will test how three-dimensional structure alters
glycosylation, elongation, and glycoprotein function. When complete, these technologies will enable biologists to
probe and design alternate glycoforms both computationally and experimentally for (1) research on the biology
of glycosylation and glycosylated molecules and (2) applications to vaccines and therapeutic biomolecule design.
预测和探测糖基转移的技术
项目摘要
糖基化是所有生命的基础。聚糖为生物分子增加了一层额外的信息,
构象和动力学,具有不同的调节作用,如稳定蛋白质折叠和信号转导
干细胞命运,并在疾病中表现突出。由于我们对糖基化作用机制的了解
继续增长,治疗性剥削的机会也在增长。新兴技术开启了
提供了一种简单、可扩展的确定的糖缀合物的生物合成的途径,
不同的应用。与此同时,出现了一套工具来预测生物分子的3D结构
快速准确地设计新的生物分子和变体。结构预测和设计工具
通过提供对聚糖作用的结构见解来改变糖生物学的潜力,
通过设计改变的和新的糖缀合物来创造新的功能。
我们的首要目标是开发互补的计算和实验方法来探测
影响糖基化和延伸的结构和环境背景。我们的研究将解决
实现这些工具所需的技术障碍,即开发方法,
糖缀合物结构和扫描实验中的交替糖型。我们的工作将创造计算
预测糖基化位点和延伸产物的算法以及探测蛋白质范围的实验工具
在特定的目标糖型。设计和预测有利候选人的计算工具,
实验将降低成本并加速糖科学的发展。实验方法
合成不同糖型将使得能够对替代糖型进行功能测试。
为了发展我们的技术,我们将通过计算预测和实验生成结构,
寡糖基转移到Im7和RNase A模型蛋白中的所有可能位点。然后我们将继续
计算预测和实验测试替代的延伸方案,这导致不同的聚糖
对于这些建筑物。总之,我们的工具集将测试三维结构如何改变
糖基化、延伸和糖蛋白功能。一旦完成,这些技术将使生物学家能够
在计算和实验上探测和设计替代糖型,用于(1)生物学研究
糖基化和糖基化的分子和(2)应用于疫苗和治疗性生物分子设计。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('JEFFREY J GRAY', 18)}}的其他基金
Prediction of the Structures of Protein Complexes
蛋白质复合物结构的预测
- 批准号:
10206954 - 财政年份:2021
- 资助金额:
$ 24.93万 - 项目类别:
Prediction of the Structures of Protein Complexes
蛋白质复合物结构的预测
- 批准号:
10407529 - 财政年份:2021
- 资助金额:
$ 24.93万 - 项目类别:
Prediction of the Structures of Protein Complexes
蛋白质复合物结构的预测
- 批准号:
10693822 - 财政年份:2021
- 资助金额:
$ 24.93万 - 项目类别:
Prediction of Structure of Therapeutic Antibodies with their Antigens
治疗性抗体结构及其抗原的预测
- 批准号:
8731999 - 财政年份:2013
- 资助金额:
$ 24.93万 - 项目类别:
Prediction of the Structure of Therapeutic Antibodies with their Antigens
治疗性抗体结构及其抗原的预测
- 批准号:
7487309 - 财政年份:2006
- 资助金额:
$ 24.93万 - 项目类别:
Prediction of the Structure of Therapeutic Antibodies with their Antigens
治疗性抗体结构及其抗原的预测
- 批准号:
8546392 - 财政年份:2006
- 资助金额:
$ 24.93万 - 项目类别:
Prediction of the Structure of Therapeutic Antibodies with their Antigens
治疗性抗体结构及其抗原的预测
- 批准号:
7680247 - 财政年份:2006
- 资助金额:
$ 24.93万 - 项目类别:
Prediction of the Structure of Therapeutic Antibodies with their Antigens
治疗性抗体及其抗原结构的预测
- 批准号:
9923648 - 财政年份:2006
- 资助金额:
$ 24.93万 - 项目类别:
Prediction of the Structure of Therapeutic Antibodies with their Antigens
治疗性抗体结构及其抗原的预测
- 批准号:
7132766 - 财政年份:2006
- 资助金额:
$ 24.93万 - 项目类别:
Prediction of the Structure of Therapeutic Antibodies with their Antigens
治疗性抗体结构及其抗原的预测
- 批准号:
7279806 - 财政年份:2006
- 资助金额:
$ 24.93万 - 项目类别:
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