Duan Lili, Guo Xiaona, Cong Yalong, Feng Guoqiang, Li Yuchen, Zhang John Z H
School of Physics and Electronics, Shandong Normal University, Jinan, China.
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.
Front Chem. 2019 Aug 6;7:540. doi: 10.3389/fchem.2019.00540. eCollection 2019.
In this study, we examined the folding processes of eight helical proteins (2I9M, TC5B, 1WN8, 1V4Z, 1HO2, 1HLL, 2KFE, and 1YYB) at room temperature using the explicit solvent model under the AMBER14SB force field with the accelerated molecular dynamics (AMD) and traditional molecular dynamics (MD), respectively. We analyzed and compared the simulation results obtained by these two methods based on several aspects, such as root mean square deviation (RMSD), native contacts, cluster analysis, folding snapshots, free energy landscape, and the evolution of the radius of gyration, which showed that these eight proteins were successfully and consistently folded into the corresponding native structures by AMD simulations carried out at room temperature. In addition, the folding occurred in the range of 40~180 ns after starting from the linear structures of the eight proteins at 300 K. By contrast, these stable folding structures were not found when the traditional molecular dynamics (MD) simulation was used. At the same time, the influence of high temperatures (350, 400, and 450 K) is also further investigated. Study found that the simulation efficiency of AMD is higher than that of MD simulations, regardless of the temperature. Of these temperatures, 300 K is the most suitable temperature for protein folding for all systems. To further investigate the efficiency of AMD, another trajectory was simulated for eight proteins with the same linear structure but different random seeds at 300 K. Both AMD trajectories reached the correct folded structures. Our result clearly shows that AMD simulation are a highly efficient and reliable method for the study of protein folding.
在本研究中，我们分别使用AMBER14SB力场下的显式溶剂模型，通过加速分子动力学（AMD）和传统分子动力学（MD），在室温下研究了八种螺旋蛋白（2I9M、TC5B、1WN8、1V4Z、1HO2、1HLL、2KFE和1YYB）的折叠过程。我们基于均方根偏差（RMSD）、天然接触、聚类分析、折叠快照、自由能景观以及回转半径的演变等几个方面，分析并比较了这两种方法获得的模拟结果，结果表明，通过在室温下进行的AMD模拟，这八种蛋白质成功且一致地折叠成了相应的天然结构。此外，从300K下八种蛋白质的线性结构开始，折叠在40~180ns范围内发生。相比之下，使用传统分子动力学（MD）模拟时未发现这些稳定的折叠结构。同时，还进一步研究了高温（350、400和450K）的影响。研究发现，无论温度如何，AMD的模拟效率都高于MD模拟。在这些温度中，300K对所有系统来说都是蛋白质折叠最合适的温度。为了进一步研究AMD的效率，在300K下对具有相同线性结构但不同随机种子的八种蛋白质模拟了另一条轨迹。两条AMD轨迹均达到了正确的折叠结构。我们的结果清楚地表明，AMD模拟是研究蛋白质折叠的一种高效且可靠的方法。
