Freddolino Peter L, Liu Feng, Gruebele Martin, Schulten Klaus
Biophys J. 2008 May 15;94(10):L75-7. doi: 10.1529/biophysj.108.131565. Epub 2008 Mar 13.
All-atom molecular dynamics (MD) simulations of protein folding allow analysis of the folding process at an unprecedented level of detail. Unfortunately, such simulations have not yet reached their full potential both due to difficulties in sufficiently sampling the microsecond timescales needed for folding, and because the force field used may yield neither the correct dynamical sequence of events nor the folded structure. The ongoing study of protein folding through computational methods thus requires both improvements in the performance of molecular dynamics programs to make longer timescales accessible, and testing of force fields in the context of folding simulations. We report a ten-microsecond simulation of an incipient downhill-folding WW domain mutant along with measurement of a molecular time and activated folding time of 1.5 microseconds and 13.3 microseconds, respectively. The protein simulated in explicit solvent exhibits several metastable states with incorrect topology and does not assume the native state during the present simulations.
蛋白质折叠的全原子分子动力学（MD）模拟能够以前所未有的详细程度分析折叠过程。不幸的是，由于难以充分采样折叠所需的微秒时间尺度，以及所使用的力场可能既无法产生正确的动力学事件序列，也无法产生折叠结构，此类模拟尚未发挥出全部潜力。因此，通过计算方法对蛋白质折叠进行的持续研究既需要提高分子动力学程序的性能以实现更长的时间尺度，也需要在折叠模拟的背景下测试力场。我们报告了对一个初始下坡折叠的WW结构域突变体进行的十微秒模拟，同时分别测量了分子时间和活化折叠时间，分别为1.5微秒和13.3微秒。在显式溶剂中模拟的蛋白质表现出几种具有错误拓扑结构的亚稳态，并且在当前模拟过程中未呈现天然状态。
