PACE Force Field for Protein Simulations. 2. Folding Simulations of Peptides
PACE Force Field for Protein Simulations. 2. Folding Simulations of Peptides
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DOI：
10.1021/ct100313a
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发表时间：
2010-11-01
影响因子：
5.5
通讯作者：
Wu, Yun-Dong
中科院分区：
文献类型：
--
作者：
Han, Wei;Wan, Cheuk-Kin;Wu, Yun-Dong
我们展示了我们最近开发的 PACE 力场在肽折叠中的应用。这些肽包括 a-螺旋（AK17 和 Fs）、β-折叠（GB1m2 和 Trpzip2）以及混合螺旋/螺旋（Trp-笼）肽。通过复制交换分子动力学（REMD），我们的力场可以将五种肽折叠成它们的天然结构，同时保持它们的稳定性相当好。我们的力场还能够捕获在之前的实验和计算研究中观察到的五种肽的重要热力学特征，例如AK17和Fs对螺旋-转角-螺旋拓扑的不同偏好，GB1p的四个疏水侧链对β-发夹稳定性的相对贡献，以及涉及Trp-H的氢键和D9/R16盐桥在稳定Trp-笼天然结构中的独特作用。此外，在 AK17、Trpzip2 和 Trp-cage 的微秒长正常 MD 模拟中观察到多次折叠和展开事件。这些模拟提供了机械信息，例如 Trpzip2 折叠机制的“zip-out”路径以及 AK.17 和 Trp-cage 的折叠时间，估计分别约为 51 +/- 43 ns 和 270 +/- 110 ns。 600 ns 的肽模拟可以在一天内完成。我们的力场的这些特征可能适用于真实蛋白质系统的热力学和动力学研究。
We present the application of our recently developed PACE force field to the folding of peptides. These peptides include a-helical (AK17 and Fs), beta-sheet (GB1m2 and Trpzip2), and mixed helical/coil (Trp-cage) peptides. With replica exchange molecular dynamics (REMD), our force field can fold the five peptides into their native structures while maintaining their stabilities reasonably well. Our force field is also able to capture important thermodynamic features of the five peptides that have been observed in previous experimental and computational studies, such as different preferences for a helix-turn-helix topology for AK17 and Fs, the relative contribution of four hydrophobic side chains of GB1p to the stability of beta-hairpin, and the distinct role of a hydrogen bond involving Trp-H, and a D9/R16 salt bridge in stabilizing the Trp-cage native structure. Furthermore, multiple folding and unfolding events are observed in our microsecond-long normal MD simulations of AK17, Trpzip2, and Trp-cage. These simulations provide mechanistic information such as a "zip-out" pathway of the folding mechanism of Trpzip2 and the folding times of AK.17 and Trp-cage, which are estimated to be about 51 +/- 43 ns and 270 +/- 110 ns, respectively. A 600 ns simulation of the peptides can be completed within one day. These features of our force field are potentially applicable to the study of thermodynamics and kinetics of real protein systems.