Re Suyong, Nishima Wataru, Miyashita Naoyuki, Sugita Yuji
RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
RIKEN Quantitative Biology Center, IMDA 6F, 1-6-5 Minatojimaminamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Biophys Rev. 2012 Sep;4(3):179-187. doi: 10.1007/s12551-012-0090-y. Epub 2012 Sep 1.
Protein-glycan recognition regulates a wide range of biological and pathogenic processes. Conformational diversity of glycans in solution is apparently incompatible with specific binding to their receptor proteins. One possibility is that among the different conformational states of a glycan, only one conformer is utilized for specific binding to a protein. However, the labile nature of glycans makes characterizing their conformational states a challenging issue. All-atom molecular dynamics (MD) simulations provide the atomic details of glycan structures in solution, but fairly extensive sampling is required for simulating the transitions between rotameric states. This difficulty limits application of conventional MD simulations to small fragments like di- and tri-saccharides. Replica-exchange molecular dynamics (REMD) simulation, with extensive sampling of structures in solution, provides a valuable way to identify a family of glycan conformers. This article reviews recent REMD simulations of glycans carried out by us or other research groups and provides new insights into the conformational equilibria of N-glycans and their alteration by chemical modification. We also emphasize the importance of statistical averaging over the multiple conformers of glycans for comparing simulation results with experimental observables. The results support the concept of "conformer selection" in protein-glycan recognition.
蛋白质-聚糖识别调控着广泛的生物学和致病过程。溶液中聚糖的构象多样性显然与它们与其受体蛋白的特异性结合不兼容。一种可能性是，在聚糖的不同构象状态中，只有一种构象异构体用于与蛋白质的特异性结合。然而，聚糖的不稳定性质使得表征其构象状态成为一个具有挑战性的问题。全原子分子动力学（MD）模拟提供了溶液中聚糖结构的原子细节，但模拟旋转异构体状态之间的转变需要相当广泛的采样。这一困难限制了传统MD模拟在二糖和三糖等小片段上的应用。副本交换分子动力学（REMD）模拟通过对溶液中的结构进行广泛采样，为识别聚糖构象异构体家族提供了一种有价值的方法。本文综述了我们或其他研究小组最近对聚糖进行的REMD模拟，并对N-聚糖的构象平衡及其化学修饰引起的变化提供了新的见解。我们还强调了对聚糖的多个构象异构体进行统计平均对于将模拟结果与实验观测值进行比较的重要性。结果支持了蛋白质-聚糖识别中的“构象异构体选择”概念。
