Department of Chemistry, Maynooth University, Maynooth, Ireland.
Hamilton Institute, Maynooth University, Maynooth, Ireland.
Nat Methods. 2024 Nov;21(11):2117-2127. doi: 10.1038/s41592-024-02464-7. Epub 2024 Oct 14.
Despite ground-breaking innovations in experimental structural biology and protein structure prediction techniques, capturing the structure of the glycans that functionalize proteins remains a challenge. Here we introduce GlycoShape ( https://glycoshape.org ), an open-access glycan structure database and toolbox designed to restore glycoproteins to their native and functional form in seconds. The GlycoShape database counts over 500 unique glycans so far, covering the human glycome and augmented by elements from a wide range of organisms, obtained from 1 ms of cumulative sampling from molecular dynamics simulations. These structures can be linked to proteins with a robust algorithm named Re-Glyco, directly compatible with structural data in open-access repositories, such as the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) and AlphaFold Protein Structure Database, or own. The quality, performance and broad applicability of GlycoShape is demonstrated by its ability to predict N-glycosylation occupancy, scoring a 93% agreement with experiment, based on screening all proteins in the PDB with a corresponding glycoproteomics profile, for a total of 4,259 N-glycosylation sequons.
尽管实验结构生物学和蛋白质结构预测技术取得了突破性的进展，但捕捉具有功能的聚糖的结构仍然是一个挑战。在这里，我们介绍 GlycoShape（https://glycoshape.org），这是一个开放获取的聚糖结构数据库和工具包，旨在在几秒钟内将糖蛋白恢复到其天然和功能形式。GlycoShape 数据库目前已有 500 多种独特的聚糖，涵盖了人类糖组，并通过来自广泛生物的元素进行了扩充，这些元素是从分子动力学模拟的 1ms 累积采样中获得的。这些结构可以通过名为 Re-Glyco 的强大算法与蛋白质相关联，该算法与 Research Collaboratory for Structural Bioinformatics Protein Data Bank（RCSB PDB）和 AlphaFold Protein Structure Database 等开放获取存储库中的结构数据直接兼容，或者与自己的结构数据兼容。通过对 PDB 中具有相应糖组学特征的所有蛋白质进行筛选，总共 4,259 个 N-糖基化序列，GlycoShape 能够预测 N-糖基化占有率，实验结果显示其具有 93%的一致性，从而证明了其质量、性能和广泛适用性。
