MD SIMULATIONS OF HYBRID/COMPLEX TYPE OLIGOSACCHARIDES--BINDING TO PROTEINS

通过分子动力学模拟，我们进一步分析了 杂合体（GlcNAc 1 Man 5GlcNAC 2）的构象偏好和 复合物（GlcNAc 1 Man 3GicNAC 2; GlcNAC 2 Man 3GlcNAC 2）型天冬酰胺连接的 寡糖和相应的二等分寡糖， 是各种高尔基体糖基转移酶的底物， 糖蛋白生物合成的前体。 的结果予以 模拟，这已发表在国际期刊， 生物大分子（1996：18;101-14），表明波动 的核心Man-Mesal，3-Man片段被限制在一个区域周围， （-30度-30度），由于平分的“面对面”布置 GlcNAc和1，3-臂上的β 1，2-GlcNAc，并与 NMR研究得出的结论。 但偶尔 这种“面对面”排列被破坏的构象是 也访问。 1，6臂的方向不仅受到 KHI的变化，而且还受到核心周围phi和psi的变化的影响 人-人，6-人连锁，如先前在MD中观察到的 刺桐七糖部分的模拟 珊瑚木凝集素 核心周围的构象 在杂种和两种复合体中，6-Man连锁是不同的 类型表明phi、psi和khi的优选值是 受在《公约》中增加或删除《公约》 β-醛，6-连接甘露糖。 构象数据与 现有的实验研究，并解释了分支 半乳糖基转移酶的特异性。 α-乳白蛋白，一种改变底物特异性的蛋白质 β-1，4-半乳糖基转移酶，不结合任何糖， 它与A、B、C、D、E和F糖的结构相似 溶菌酶的结合位点。 溶菌酶结合六糖， （-NAM-NAG-）3，在A至F位点，其中D-E是催化位点。 计算机建模方法正被用来解决这个问题“为什么 α-乳白蛋白不结合任何糖，而其同源物 蛋白质c型溶菌酶，它与它具有序列和结构 同源性，结合和水解低聚糖”？ 计算机建模 方法被用于研究单糖与C的结合， α-乳白蛋白和溶菌酶的B和D位点。

By using molecular dynamics (MD) simulations we have further analyzed the conformational preferences of hybrid (GlcNAc1Man5GIcNAC2) and complex (GlcNAc1Man3GicNAC2; GlcNAC2Man3GlcNAC2) type asparagine-linked oligosaccharides and the corresponding bisected oligosaccharides that are the substrates for various Golgi glycosyltransferases and precursors in the biosynthesis of glycoproteins. The results of these simulations, which have been published in the International Journal of Biological Macromolecules (1996:18;101-14), show that the fluctuations of the core Man-alphal,3-Man fragment are restricted to a region around (-30degrees-30degrees) due to a 'face-to-face' arrangement of bisecting GlcNAc and the beta1,2-GlcNAc on the 1,3-arm and are in agreement with the conclusions drawn from NMR studies. However, occasionally conformations where such a 'face-to-face' arrangement is disrupted are also accessed. 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-alphal,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-alphal,6-Man linkage is different in the hybrid and the two complex types suggesting that the preferred values of phi, psi, and khi are affected by the addition or deletion of saccharides to the alphal,6-linked mannose. The conformational data are in agreement with the available experimental studies and also explain the branch specificity of galactosyltransferases. alpha-Lactalbumin, a protein that modifies the substrate specificity of beta-1,4-galactosyltransferase, does not bind any sugar even though it does show structural similarity with the A, B, C, D, E, & F sugar binding sites of lysozyme. Lysozyme binds a hexasaccharide, (-NAM-NAG-)3, in the A to F sites, where D-E is the catalytic site. Computer modeling methods are being used to address the question "why alpha-lactalbumin does not bind any sugar while as its homologous protein c-type lysozyme, with which it has both sequence and structural homology, does bind and hydrolyse oligosaccharides"? Computer modeling approach is being used to study the binding of monosaccharides to C, B and D sites of alpha-lactalbumin and lysozyme.