Frank Martin, Bohne-Lang Andreas, Wetter Thomas, Lieth Claus-W von der
DKFZ (German Cancer Research Centre), Molecular Modelling, INF 280, 69120 Heidelberg, Germany.
In Silico Biol. 2002;2(3):427-39.
Glycosylated proteins are ubiquitous components of extracellular matrices and cellular surfaces where their oligosaccharide moieties are implicated in a wide range of cell-cell and cell-matrix recognition events. Glycans constitute highly flexible molecules. Only a small number of glycan X-ray structures is available for which sufficient electron density for an entire oligosaccharide chain has been observed. An unambiguous structure determination based on NMR-derived geometric constraints alone is often not possible. Time consuming computational approaches such as Monte Carlo calculations and molecular dynamics simulations have been widely used to explore the conformational space accessible to complex carbohydrates. The generation of a comprehensive data base for N-glycan fragments based on long time molecular dynamics simulations is presented. The fragments are chosen in such a way that the effects of branched N-glycan structures are taken into account. The prediction database constitutes the basis of a procedure to generate a complete set of all possible conformations for a given N-glycan. The constructed conformations are ranked according to their energy content. The resulting conformations are in reasonable agreement with experimental data. A web interface has been established (http://www.dkfz.de/spec/glydict/), which enables to input any N-glycan of interest and to receive an ensemble of generated conformations within a few minutes.
糖基化蛋白是细胞外基质和细胞表面普遍存在的成分，其寡糖部分参与了广泛的细胞间和细胞与基质的识别事件。聚糖构成了高度灵活的分子。仅有少数聚糖的X射线结构可用于观察到整个寡糖链有足够的电子密度。仅基于核磁共振衍生的几何约束进行明确的结构测定通常是不可能的。诸如蒙特卡罗计算和分子动力学模拟等耗时的计算方法已被广泛用于探索复杂碳水化合物可及的构象空间。本文提出了基于长时间分子动力学模拟生成N-聚糖片段综合数据库的方法。片段的选择方式考虑了分支N-聚糖结构的影响。该预测数据库构成了为给定N-聚糖生成所有可能构象的完整集合的程序基础。构建的构象根据其能量含量进行排序。所得构象与实验数据合理一致。已建立了一个网络界面（http://www.dkfz.de/spec/glydict/），它能够输入任何感兴趣的N-聚糖，并在几分钟内接收生成的构象集合。
