Almond A, Sheehan J K, Brass A
Division of Biochemistry, School of Biological Sciences, University of Manchester, UK.
Glycobiology. 1997 Jul;7(5):597-604. doi: 10.1093/glycob/7.5.597.
Hyaluronan is an unusually stiff polymer when in aqueous solution, which has important consequences for its biological function. Molecular dynamics simulations of hyaluronan disaccharides have been performed, with explicit inclusion of water, to determine the molecular basis of this stiffness, and to investigate the dynamics of the glycosidic linkages. Our simulations reveal that stable sets of hydrogen bonds frequently connect the neighboring residues of hyaluronan. Water caging around the glycosidic linkage was observed to increase the connectivity between sugars, and further constrain them. This, we propose, explains the unusual stiffness of polymeric hyaluronan. It would allow the polysaccharide to maintain local secondary structure, and occupy large solution domains consistent with the visco-elastic nature of hyaluronan. Simulations in water showed no significant changes on inclusion of the exoanomeric effect. This, we deduced, was due to hyaluronan disaccharides ordering first shell water molecules. In some cases these waters were observed to transiently induce conformational change, by breaking intramolecular hydrogen bonds.
透明质酸在水溶液中是一种异常坚硬的聚合物，这对其生物学功能具有重要影响。已对透明质酸二糖进行了分子动力学模拟，并明确包含水，以确定这种硬度的分子基础，并研究糖苷键的动力学。我们的模拟表明，稳定的氢键集经常连接透明质酸的相邻残基。观察到糖苷键周围的水笼增加了糖之间的连接性，并进一步限制了它们。我们认为，这解释了聚合透明质酸异常的硬度。它将允许多糖维持局部二级结构，并占据与透明质酸的粘弹性性质一致的大溶液区域。在水中的模拟显示，包含异头效应后没有显著变化。我们推断，这是由于透明质酸二糖使第一壳层水分子有序排列。在某些情况下，观察到这些水通过打破分子内氢键而短暂诱导构象变化。
