German Research School for Simulation Science, FZ-Juelich and RWTH Aachen, Jülich, Germany.
FEBS Lett. 2011 Oct 3;585(19):3086-9. doi: 10.1016/j.febslet.2011.08.036. Epub 2011 Aug 30.
The first 17 amino acids of Huntingtin protein (N17) play a crucial role in the protein's aggregation. Here we predict its free energy landscape in aqueous solution by using bias exchange metadynamics. All our findings are consistent with experimental data. N17 populates four main kinetic basins, which interconvert on the microsecond time-scale. The most populated basin (about 75%) is a random coil, with an extended flat exposed hydrophobic surface. This might create a hydrophobic seed promoting Huntingtin aggregation. The other main populated basins contain helical conformations, which could facilitate N17 binding on its cellular targets.
亨廷顿蛋白的前 17 个氨基酸（N17）在蛋白质聚集过程中起着至关重要的作用。在这里，我们使用偏置交换元动力学方法预测其在水溶液中的自由能景观。我们所有的发现都与实验数据一致。N17 分布在四个主要的动力学基态中，它们在微秒时间尺度上相互转换。最常见的基态（约 75%）是一个无规卷曲，具有扩展的平坦暴露的疏水面。这可能会形成一个促进亨廷顿蛋白聚集的疏水性种子。其他主要的基态包含螺旋构象，这可能有助于 N17 与其细胞靶标结合。
