【摘要】 用分子动力学(MD)模拟方法设计了两个模拟时间为600 ps的对比计算机模拟实验,研究了R6态的胰岛素六聚体在水溶液中的构象柔性。通过对MD模拟所得到的轨迹的分析发现,包含锌离子和苯酚的胰岛素六聚体体系的构象柔性弱于不含锌离子和苯酚的胰岛素六聚体体系,对于不包含锌离子和苯酚的体系,胰岛素六聚体的构象柔性表现得较为突出,特别是在实验研究认为与胰岛素和受体结合位点有关的每个单体的B链羧端的β折叠部分,发生了快速而显著的构象变化,表现出了很大的构象柔性。这些模拟结果与实验观测结果相吻合。更多还原

【Abstract】 In order to study the flexibility of insulin hexamer in solution, two 600 ps molecular dynamics (MD) simulations of the protein complex, R-state human insulin hexamer system, were carried out respectively. Through the comparison analysis for two MD simulation data, it was found that for the system with Zn2+ ions and phenol, the conformational flexibility of insulin hexamer was decreased. However, in the absence of Zn2+ and phenol, the insulin hexamer exhibits a higher degree of conformational flexibility in aqueous solution. The remarkable and rapid conformational changes of the β-sheet at C-terminus of the B-chain in every insulin monomer provide a structural basis for insulin to bind with its receptor. These results are in good agreement with the experimental observation.更多还原