Tools to enable non-specialists to model glycoconjugates and glycan-protein interactions

项目摘要 为了确保生命科学的持续发展，有必要了解 碳水化合物（聚糖）在人类健康和疾病中的重要性和功能 生命科学的研究人员。目前人类生理学的这些方面的知识是相当可观的，但 其中大部分只有糖科学专家才能获得。最近，有相当大的进展， 在碳水化合物的计算机建模技术中，特别是那些与人体生理学相关的碳水化合物， 特别是关于它们与蛋白质的相互作用。然而，与大多数相关领域一样， 糖生物学，获得这些技术仍然是有限的，因为只有专家有技术 使用它们所需的技能。该项目旨在开发基于互联网的软件和教育 这些资源是免费提供给所有人的，是专门为研究人员在生活中使用而设计的。 以理工科为重该项目的长期目标是丰富基于糖的技术的发现， 促进人类健康和延长寿命的程序。 我们建议生成一套在线工具，“计算糖科学门户”（CGP）， 专门供非糖生物学或计算生物医学领域专家的生物医学研究人员使用。 以理工科为重这些工具将建立在GLYCAM-Web平台上，该平台已经广泛托管了几个在线工具 用于糖科学界。由于GLYCAM-Web的基础设施最近经历了 重大升级，有一个坚实的技术基础，在此基础上扩大现有的能力，并增加新的 一个 特别是，我们建议将已建立的技术作为工具，使研究人员能够生成 分析聚糖-蛋白质复合物的计算机模型，预测糖蛋白的3D结构， 糖脂，并验证3D模型对实验数据。这些工具将使研究人员能够 检查结合复合物中亲和力的起源，以更好地理解聚糖阵列数据， 糖基化的转化方面，并将他们的研究结果与NMR结果进行比较 实验等等。但是，最重要的是，我们将确保这些工具可供研究人员使用 具有一般生物医学知识，不一定熟悉糖生物学或计算生物学， 糖科学我们将通过两种方式确保这一点。第一，我们将咨询这些领域的研究人员， 从这些工具中找出他们需要的东西。只要有可能，我们将构建工具来反映其 建议.第二，也是基于这些咨询，我们将产生高质量，免费提供，在线 为这些研究人员设计的教育材料，描述了工具和技术。

Project Summary To ensure the continued advancement of the life sciences, it is necessary that an understanding of the significance and functions of carbohydrates (glycans) in human health and disease be widely available to all researchers in the life sciences. Current knowledge of these aspects of human physiology is considerable, but much of it is only available to experts in the glycosciences. Recently, there have been considerable advances in techniques computer modeling of carbohydrates, particularly those of relevance to human physiology and especially with regard to their interactions with proteins. However, as with most fields of relevance to glycobiology, access to these techniques has remained limited because only experts have the technological skills necessary to use them. This project proposes to develop internet-based software and educational resources that are freely available to all and that are designed especially for use by researchers in the life sciences. The long-term goal of this project is to enrich the discovery of glyco-based technologies and procedures that promote human health and extend life. We propose to generate a suite of online tools, “Computational Glycosciences Portal” (CGP), designed specifically for use by biomedical researchers who are not specialists in glycobiology or in the computational sciences. The tools will be built on the GLYCAM-Web platform that already hosts several online tools widely used in the glycoscience community. Since the infrastructure for GLYCAM-Web has recently undergone significant upgrades, there is a solid technological base upon which to expand current capabilities and add new ones. In particular, we propose to implement established techniques as tools that will allow researchers to generate and analyze computer models of glycan-protein complexes, to predict the 3D structures of glycoproteins and glycolipids, and to validate the 3D models against experimental data. These tools will allow researchers to examine the origins of affinity in bound complexes, to better understand glycan array data, to investigate the transformative aspects of glycosylation, and to compare results of their studies to results from NMR experiments among others. But, most importantly, we will ensure that these tools are usable by researchers with general biomedical knowledge who are not necessarily conversant with glycobiology or the computational glycosciences. We will ensure this in two ways. One, we will consult with researchers in these fields to find out what they need from tools such as these. Wherever possible, we will construct the tools to reflect their advice. Two, also based on these consultations, we will generate high-quality, freely-available, online educational materials, designed for these researchers, that describe the tools and techniques.