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

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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.