英国南安普顿大学Elisa Fadda研究组使用GlycoShape恢复蛋白糖基化。这一研究成果于2024年10月14日在线发表在国际学术期刊《自然—方法学》上。

研究人员报道了GlycoShape（https://glycoshape.org），一个开放访问的糖基结构数据库和工具箱，旨在秒级恢复糖蛋白的天然和功能形式。GlycoShape数据库目前包含超过500种独特糖基，涵盖了人类糖组，并通过分子动力学模拟的1毫秒累计采样扩展至多种生物体的元素。

这些结构可以通过名为Re-Glyco的强大算法与蛋白质相连接，直接兼容开放存取库中的结构数据，如结构生物信息学蛋白质数据库（RCSB PDB）和AlphaFold蛋白质结构数据库，或用户自有数据。

GlycoShape的质量、性能和广泛适用性通过其预测N-糖基化占位的能力得到了证明。基于筛选PDB中所有具有相应糖蛋白组学数据的蛋白质，研究人员共计获得4259个N-糖基化位点，其预测与实验数据的吻合率达到93%。

据悉，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创新，但捕捉功能化蛋白质的糖基结构仍是一个挑战。

附：英文原文

Title: Restoring protein glycosylation with GlycoShape

Author: Ives, Callum M., Singh, Ojas, DAndrea, Silvia, Fogarty, Carl A., Harbison, Aoife M., Satheesan, Akash, Tropea, Beatrice, Fadda, Elisa

Issue&Volume: 2024-10-14

Abstract: 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 1ms 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.

DOI: 10.1038/s41592-024-02464-7

Source: https://www.nature.com/articles/s41592-024-02464-7