Department of Chemistry and Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, Texas 78712, USA.
J Chem Phys. 2017 Oct 21;147(15):152707. doi: 10.1063/1.4993228.
Recent single-molecule experiments probed transition paths of biomolecular folding and, in particular, measured the time biomolecules spend while crossing their free energy barriers. A surprising finding from these studies is that the transition barriers crossed by transition paths, as inferred from experimentally observed transition path times, are often lower than the independently determined free energy barriers. Here we explore memory effects leading to anomalous diffusion as a possible origin of this discrepancy. Our analysis of several molecular dynamics trajectories shows that the dynamics of common reaction coordinates used to describe protein folding is subdiffusive, at least at sufficiently short times. We capture this effect using a one-dimensional fractional Brownian motion (FBM) model, in which the system undergoes a subdiffusive process in the presence of a potential of mean force, and show that this model yields much broader distributions of transition path times with stretched exponential long-time tails. Without any adjustable parameters, these distributions agree well with the transition path times computed directly from protein trajectories. We further discuss how the FBM model can be tested experimentally.
最近的单分子实验探究了生物分子折叠的转变路径，特别是测量了生物分子穿越自由能势垒时所花费的时间。这些研究的一个惊人发现是，通过实验观察到的转变路径时间推断出的转变势垒，往往低于独立确定的自由能势垒。在这里，我们探讨了导致反常扩散的记忆效应，将其作为这种差异的可能起源。我们对几个分子动力学轨迹的分析表明，用于描述蛋白质折叠的常见反应坐标的动力学至少在足够短的时间内是亚扩散的。我们使用一维分数布朗运动（FBM）模型来捕获这种效应，在该模型中，系统在平均力势的存在下经历亚扩散过程，并表明该模型产生了具有扩展指数长尾的转变路径时间的更广泛分布。没有任何可调参数，这些分布与直接从蛋白质轨迹计算得到的转变路径时间非常吻合。我们进一步讨论了如何通过实验来检验 FBM 模型。
