CONFORMATIONAL ANALYSIS OF HIGH MANNOSE OLIGOSACCHARIDES BY MD SIMULATIONS

天冬酰胺连接低聚糖的构象分析 分子动力学(MD)模拟进一步扩展到 混合型和复合型中间结构，它们是 不同糖基转移酶的底物和前体 最终杂交型和复合型低聚糖的生物合成。这个 模拟表明，在二等分GlcNAc存在的情况下， 核心Man-α1，3-Man片段的涨落仅限于 (30度，30度)左右的区域 复杂类型，这与从 核磁共振研究。然而，大于0%的phi和 围绕Man Alpha1、3-Man片段的PSI也以对分形式访问 低聚糖，尽管是偶尔的，表明 1，3-臂在不存在的情况下可访问的构象 一分为二的GlcNAc不是立体化学消除的。这个 1，6-臂的取向不仅受khi变化的影响，而且 也通过核心人周围的phi和psi的变化-α1，6-人 如先前在分子动力学模拟中观察到的那样 刺桐凝集素的七糖部分。这个 核心的人-α1，6-人连锁的构象不同于 混合和两种复杂的类型表明，首选 Phi、Psi、Khi的值受添加或删除 糖链与α-1，6-甘露糖相连。这些分子动力学 研究使光谱和生化观察合理化，如 α-甘露糖苷酶切割α-1，2-连接甘露糖的速率， β-1，4-半乳糖基转移酶在双天线中的作用 低聚糖与寡糖的结合亲和力 去唾液酸糖蛋白受体的配体。评选结果 现在和我们以前的MD模拟已经在一个 特邀评论文章。

The conformational analysis of asparagine-linked oligosaccharides by molecular dynamics (MD) simulations were further extended to the hybrid and complex type intermediate structures which are the substrates for various glycosyl-transferases and precursors in the biosynthesis of final hybrid and complex type oligosaccharides. The simulations show that in the presence of the bisecting GlcNAc, the fluctuations of the core Man-alpha 1,3-Man fragment are restricted to a region around (30 degrees,30 degrees) in both the hybrid and complex types, which is in agreement with the conclusions drawn from NMR studies. However, conformations greater than 0 percent of phi and psi around the Man alpha1,3-Man fragment are also accessed in bisected oligosaccharides, albeit occasionally, suggesting that the conformations that are accessible for the 1,3-arm in the absence of the bisecting GlcNAc, are not stereochemically eliminated. The orientation of the 1,6-arm is affected not only by changes in khi, but also by changes in phi and psi around the core Man-alpha1,6-Man linkage as was observed previously in the MD simulations of the heptasaccharide moiety of the Erythrina corallodendron lectin. The conformation around the core Man-alpha1,6-Man linkage is different in the hybrid and the two complex types suggesting that the preferred values of phi, psi, khi are affected by the addition or deletion of saccharides to the alpha1,6-linked mannose. These molecular dynamics studies rationalize spectroscopic and biochemical observations like rate of cleavage of alpha1,2-linked mannoses by alpha-mannosidases, action of beta-1,4-galactosyl-transferase on biantennary oligosaccharides, and the binding affinities of oligosaccharide ligands to the asialoglycoprotein receptor. The results of the present and our previous MD simulations have been summarized in an invited review article.