Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
J Chem Phys. 2011 Oct 14;135(14):141104. doi: 10.1063/1.3650700.
Conjugating flexible polymers (such as oligosaccharides) to proteins or confining a protein in a restricted volume often increases protein thermal stability. In this communication, we investigate the interplay between conjugation and confinement which is not trivial as the magnitude and the mechanism of stabilization are different in each instance. Using coarse-grained computational approach the folding biophysics is studied when the protein is placed in a sphere of variable radius and is conjugated to 0-6 mono- or penta-saccharides. We observe a synergistic effect on thermal stability when short oligosaccharides are attached and the modified protein is confined in a small cage. However, when large oligosaccharides are added, a conflict between confinement and glycosylation arises as the stabilizing effect of the cage is dramatically reduced and it is almost impossible to further stabilize the protein beyond the mild stabilization induced by the sugars.
将柔性聚合物（如寡糖）与蛋白质连接，或在有限的体积内限制蛋白质，通常会增加蛋白质的热稳定性。在本通讯中，我们研究了连接和限制之间的相互作用，由于每种情况下稳定化的幅度和机制不同，因此这并不是微不足道的。使用粗粒度的计算方法，当蛋白质被放置在可变半径的球体中并与 0-6 个单糖或五糖连接时，我们研究了折叠生物物理学。当连接短的寡糖并将修饰的蛋白质限制在小笼中时，观察到协同热稳定性效应。然而，当添加较大的寡糖时，限制和糖基化之间会出现冲突，因为笼的稳定作用会大大降低，并且几乎不可能进一步稳定蛋白质，超过糖所诱导的温和稳定。
