【作者】 王维宴；

【导师】 王存新； 陈慰祖；

【作者基本信息】 北京工业大学 ， 流体力学， 2002， 硕士

【摘要】 分子动力学(MD)模拟已经成为生物大分子理论研究的一种重要工具。MD模拟不但能够在微观层次上理解和解释实验数据，而且在用实验手段无法研究或者实验研究花费昂贵的情况下更是显示出它的优势。模拟的结果对于理解蛋白质分子体系的相互作用和蛋白质的生物功能，对于在分子、原子结构层次上了解生命现象的基本过程和本质具有重要意义。 本论文用MD模拟方法设计了两个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稳定性和构象柔性，以及苯酚和锌离子对结构稳定性和构象柔性的影响。MD模拟使用GROMOS96程序及其力场进行。通过对这两个模拟所得到的轨迹在原子的平均位置、方均根涨落、方均根偏差、单体之间相互作用、氢键网络、二级结构等方面进行的比较分析发现，对于包含锌离子和苯酚的体系，胰岛素六聚体的稳定性得到了增强，但其构象柔性却受到了削弱；对不含锌离子和苯酚的体系，胰岛素六聚体的稳定性明显减弱，构象柔性却表现得较为突出，在这种情况下，胰岛素六聚体还表现出解聚的倾向。 MD模拟结果与实验结果相吻合。该研究对理解胰岛素的基本属性以及蛋白质聚集体的相互作用机制与稳定性十分重要，还可以为蛋白质工程的分子设计提供有用的信息。更多还原

【Abstract】 Molecular dynamics (MD) simulation has become an extremely powerful tool not only to understand and interpret the experiments at the microscopic level, but also to study regions which are not accessible experimentally or imply very expensive experiments. The result of MD simulations is also very useful not only to understand the essential process and nature of life phenomena at the atomic and molecular level, but also to understand the biological function and interactions between proteins.In order to study the flexibility and stability of insulin hexamer in solution and the role of Zn2+ and phenol, two 600 ps MD simulations of the R-state human insulin hexamer system were carried out respectively. The two MD simulations were carried out with the GROMOS96 package and its force field. The MD simulation data were analyzed in terms of average atomic positions, root mean square (RMS) fluctuations, monomer-monomer interactions, hydrogen bond (H-bond) network, secondary structure, and so on. Through the comparison, we found that when the system includes Zn2+ ions and phenol, the stability of insulin hexamer is enhanced, but the conformational flexibility related to its biological activity is decreased. In addition, the insulin hexamer tends to dissociate in the absence of Zn2+ and phenol.These simulation results agree well with the experimental data, which deepen and increase our understanding of essential properties of the insulin molecules, and provide a basis for the rational design of insulin pharmaceutical preparations.更多还原