ABI Innovation: Development of Glycan Modeling and Simulation Toolset

ABI Innovation：聚糖建模和模拟工具集的开发

• 批准号: 1561372
• 负责人: Wonpil Im
• 金额: $ 54.68万
• 依托单位: University of Kansas Center for Research Inc
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1561372&HistoricalAwards=false
• 关键词: ABI; Innovation; Development; Glycan; Modeling

Carbohydrates are sugars or chains of sugars that are also referred to as glycans. They can can be covalently attached to proteins (glycoproteins) and lipids (glycolipids), or exist as small, soluble molecules. Experimental techniques for studying glycans are not as well developed as for other types of biomolecules, including a lack of computational tools. This means it can be hard to decide which glycans contribute to protein function, how they act to modulate this function, and how to modify them to optimize interesting properties. Structural records of proteins, including glycosylated proteins, are appearing in ever larger numbers in the Protein Data Bank (PDB). By selecting these glycosylated protein structures for deeper investigation with sophisticated computational tools, a knowledge-based approach to understanding the relationship between their structure, function and biological roles can be built. Knowledge based approaches allow both top-down understanding of biological roles, and bottom-up simulations of structural fluctuations at the atomic level; the latter provide very deep insight into how different glycans affect the folding and function of modified proteins. In addition, most proteins in cell membranes are glycosylated, which is important to cell recognition and signaling; more realistic modeling of biological membranes, provided by the CHARMM-GUI Membrane Builder toolset, will further enrich the available repertoire of membrane structure simulations. This project aims to achieve these goals by developing a comprehensive toolset for glycan modeling and simulation. Both graduate and undergraduate students will be trained in the interdisciplinary computational structural glycobiology. In particular, this project will raise the scientific literacy of the research community through the publication of research results and workshop participation. The main objective of this project is to develop a computational toolset for modeling and simulation of glycan-containing biological systems and to acquire an in-depth and molecular-level understanding of glycan structure, dynamics, and function in the context of glycoproteins, glycolipids, and protein-glycan complexes. A comprehensive toolset for the computational analysis, modeling, and simulation of glycoconjugates and glycan-associated complexes will be developed. This tool set will include (1) Glycan Modeler, a tool for structure prediction of protein-linked glycans from their primary sequences; (2) GLYSUM, the GLYcan monosaccharide SUbstitution Matrix, the glycan equivalent to the BLOSUM matrix; (3) GLDB, Glycan Ligand Database for easy retrieval of protein-glycan interaction patterns and motifs in the PDB; (4) GBS-Predictor, a template-based tool to predict potential glycan binding sites (GBS) in a target protein; and (5) glycolipid-containing Membrane Builder, an intuitive tool to build a complex membrane system containing glycolipids. This project also seeks to foster synergistic scientific research and education on glycan structure, dynamics, and function by making resulting tools available http://www.glycanstructure.org and http://www.charmm-gui.org.

碳水化合物是糖或糖链，也称为聚糖。它们可以共价连接到蛋白质（糖蛋白）和脂质（糖脂）上，也可以作为小的可溶性分子而存在。用于研究聚糖的实验技术不像其他类型的生物分子那样发达，包括缺乏计算工具。这意味着很难确定哪种聚糖有助于蛋白质功能，它们如何调节此功能以及如何修改它们以优化有趣的属性。包括糖基化蛋白在内的蛋白质的结构记录在蛋白质数据库（PDB）中越来越多。通过选择这些糖基化的蛋白质结构来使用复杂的计算工具进行更深入的研究，可以建立一种基于知识的方法来理解其结构，功能和生物学作用之间的关系。基于知识的方法允许对生物学作用的自上而下的理解，以及对原子水平上结构波动的自下而上的模拟。后者对不同的聚糖如何影响改良蛋白的折叠和功能提供了非常深入的见解。另外，细胞膜中的大多数蛋白质都是糖基化的，这对于细胞识别和信号传导很重要。由Charmm-GUI膜构建器工具集提供的生物膜的更现实的模型将进一步丰富膜结构模拟的可用曲目。该项目旨在通过开发用于聚糖建模和仿真的全面工具集来实现这些目标。研究生和本科生都将接受跨学科计算结构糖生物学的培训。特别是，该项目将通过发布研究结果和研讨会参与来提高研究界的科学素养。该项目的主要目的是开发一种计算工具集，用于建模和模拟含聚糖的生物系统，并在糖蛋白，糖脂，糖脂和蛋白质 - 聚糖络合物中对聚糖结构，动态和功能的深入和分子级别的理解。将开发用于计算分析，建模和模拟糖缀合物和聚糖相关复合物的综合工具集。该工具集将包括（1）Glycan Modeler，这是一种从其主要序列中蛋白质连接聚糖进行结构的工具； （2）Glysum，Glycan单糖取代基质，与膨胀基质相当的聚糖； （3）GLDB，聚糖配体数据库，以便于PDB中的蛋白质 - 聚糖相互作用模式和基序轻松检索； （4）GBS-PREDICTOR，这是一种基于模板的工具，可预测靶蛋白中潜在的聚糖结合位点（GB）； （5）含糖胶质的膜构建器，这是一种直观的工具，可建造一个复杂的膜系统，其中含有糖脂。该项目还旨在通过提供产生的工具http://www.glycastructure.org和http://www.charmm-gui.org来培养有关聚糖结构，动态和功能的协同科学研究和教育。