Department of Physics, Tampere University of Technology, FI-33101 Tampere, Finland.
SAR QSAR Environ Res. 2009 Oct;20(7-8):595-609. doi: 10.1080/10629360903438198.
We used the crystal structure of prolyl oligopeptidase (POP) with bound Z-pro-prolinal (ZPP) inhibitor (Protein Data Bank (PDB) structure 1QFS) to perform an intensive molecular dynamics study of the POP-ZPP complex. We performed 100 ns of simulation with the hemiacetal bond, through which the ZPP is bound to the POP, removed in order to better investigate the binding cavity environment. From basic analysis, measuring the radius of gyration, root mean square deviation, solvent accessible surface area and definition of the secondary structure of protein, we determined that the protein structure is highly stable and maintains its structure over the entire simulation time. This demonstrates that such long time simulations can be performed without the protein structure losing stability. We found that water bridges and hydrogen bonds play a negligible role in binding the ZPP thus indicating the importance of the hemiacetal bond. The two domains of the protein are bound by a set of approximately 12 hydrogen bonds, specific to the particular POP protein.
我们使用脯氨酰寡肽酶 (POP) 与结合的 Z-脯-脯氨酰 (ZPP) 抑制剂的晶体结构（蛋白质数据库 (PDB) 结构 1QFS）对 POP-ZPP 复合物进行了深入的分子动力学研究。我们进行了 100 ns 的模拟，其中通过半缩醛键去除了与 POP 结合的 ZPP，以便更好地研究结合腔环境。通过基本分析，测量了旋转半径、均方根偏差、溶剂可及表面积和蛋白质二级结构的定义，我们确定蛋白质结构非常稳定，并在整个模拟时间内保持其结构。这表明可以在不使蛋白质结构失去稳定性的情况下进行如此长时间的模拟。我们发现，水桥和氢键在结合 ZPP 方面的作用可以忽略不计，这表明半缩醛键的重要性。蛋白质的两个结构域通过一组约 12 个氢键结合，这些氢键是特定于特定的 POP 蛋白的。
