Departments of Biological Sciences and Bioengineering, Lehigh University, Bethlehem, PA, USA.
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.
Glycobiology. 2019 Apr 1;29(4):320-331. doi: 10.1093/glycob/cwz003.
Characterizing glycans and glycoconjugates in the context of three-dimensional structures is important in understanding their biological roles and developing efficient therapeutic agents. Computational modeling and molecular simulation have become an essential tool complementary to experimental methods. Here, we present a computational tool, Glycan Modeler for in silico N-/O-glycosylation of the target protein and generation of carbohydrate-only systems. In our previous study, we developed Glycan Reader, a web-based tool for detecting carbohydrate molecules from a PDB structure and generation of simulation system and input files. As integrated into Glycan Reader in CHARMM-GUI, Glycan Modeler (Glycan Reader & Modeler) enables to generate the structures of glycans and glycoconjugates for given glycan sequences and glycosylation sites using PDB glycan template structures from Glycan Fragment Database (http://glycanstructure.org/fragment-db). Our benchmark tests demonstrate the universal applicability of Glycan Reader & Modeler to various glycan sequences and target proteins. We also investigated the structural properties of modeled glycan structures by running 2-μs molecular dynamics simulations of HIV envelope protein. The simulations show that the modeled glycan structures built by Glycan Reader & Modeler have the similar structural features compared to the ones solved by X-ray crystallography. We also describe the representative examples of glycoconjugate modeling with video demos to illustrate the practical applications of Glycan Reader & Modeler. Glycan Reader & Modeler is freely available at http://charmm-gui.org/input/glycan.
在三维结构的背景下研究糖链和糖缀合物对于理解它们的生物学功能和开发有效的治疗剂非常重要。计算建模和分子模拟已成为实验方法的重要补充工具。在这里，我们介绍了一种计算工具，Glycan Modeler，用于目标蛋白质的 N-/O-糖基化的计算模拟和碳水化合物系统的生成。在我们之前的研究中，我们开发了 Glycan Reader，这是一种基于网络的工具，用于从 PDB 结构中检测碳水化合物分子，并生成模拟系统和输入文件。作为集成到 CHARMM-GUI 中的 Glycan Reader 的一部分，Glycan Modeler（Glycan Reader & Modeler）可以使用来自 Glycan Fragment Database（http://glycanstructure.org/fragment-db）的 PDB 糖模板结构，根据给定的糖序列和糖基化位点生成糖链和糖缀合物的结构。我们的基准测试表明，Glycan Reader & Modeler 对各种糖序列和靶蛋白具有普遍适用性。我们还通过对 HIV 包膜蛋白进行 2-μs 分子动力学模拟研究了模型化糖结构的结构特性。模拟结果表明，由 Glycan Reader & Modeler 构建的模型化糖结构具有与 X 射线晶体学方法确定的结构特征相似的结构特征。我们还通过视频演示描述了糖缀合物建模的代表性示例，以说明 Glycan Reader & Modeler 的实际应用。Glycan Reader & Modeler 可在 http://charmm-gui.org/input/glycan 免费获得。
