College of Physics and Electronics, Shandong Normal University, Jinan 250014, China.
J Am Chem Soc. 2010 Aug 18;132(32):11159-64. doi: 10.1021/ja102735g.
We report direct folding of a 17-residue helix protein (pdb:2I9M) by standard molecular dynamics simulation (single trajectory) at room temperature with implicit solvent. Starting from a fully extended structure, 2I9M successfully folds into the native conformation within 16 ns using adaptive hydrogen bond-specific charges to take into account the electrostatic polarization effect. Cluster analysis shows that conformations in the native state cluster have the highest population (78.4%) among all sampled conformations. Folding snapshots and the secondary structure analysis demonstrate that the folding of 2I9M begins at terminals and progresses toward the center. A plot of the free energy landscape indicates that there is no significant free energy barrier during folding, which explains the observed fast folding speed. For comparison, exactly the same molecular dynamics simulation but carried out under existing AMBER charges failed to fold 2I9M into native-like structures. The current study demonstrates that electrostatic polarization of intraprotein hydrogen bonding, which stabilizes the helix, is critical to the successful folding of 2I9m.
我们报告了在室温下使用隐溶剂通过标准分子动力学模拟（单轨迹）直接折叠 17 残基螺旋蛋白（pdb：2I9M）。从完全展开的结构开始，使用自适应氢键特定电荷成功地在 16 ns 内将 2I9M 折叠成天然构象，以考虑静电极化效应。聚类分析表明，在所有采样构象中，天然状态聚类的构象具有最高的种群（78.4%）。折叠快照和二级结构分析表明，2I9M 的折叠从末端开始并向中心推进。自由能景观图表明，在折叠过程中没有明显的自由能障碍，这解释了观察到的快速折叠速度。相比之下，在现有的 AMBER 电荷下进行完全相同的分子动力学模拟未能将 2I9M 折叠成类似天然的结构。本研究表明，稳定螺旋的蛋白质内氢键的静电极化对于 2I9m 的成功折叠至关重要。
