Li Hongzhi, Min Donghong, Liu Yusong, Yang Wei
School of Computational Science, Florida State University, Tallahassee, Florida 32306, USA.
J Chem Phys. 2007 Sep 7;127(9):094101. doi: 10.1063/1.2769356.
To overcome the possible pseudoergodicity problem, molecular dynamic simulation can be accelerated via the realization of an energy space random walk. To achieve this, a biased free energy function (BFEF) needs to be priori obtained. Although the quality of BFEF is essential for sampling efficiency, its generation is usually tedious and nontrivial. In this work, we present an energy space metadynamics algorithm to efficiently and robustly obtain BFEFs. Moreover, in order to deal with the associated diffusion sampling problem caused by the random walk in the total energy space, the idea in the original umbrella sampling method is generalized to be the random walk in the essential energy space, which only includes the energy terms determining the conformation of a region of interest. This essential energy space generalization allows the realization of efficient localized enhanced sampling and also offers the possibility of further sampling efficiency improvement when high frequency energy terms irrelevant to the target events are free of activation. The energy space metadynamics method and its generalization in the essential energy space for the molecular dynamics acceleration are demonstrated in the simulation of a pentanelike system, the blocked alanine dipeptide model, and the leucine model.
为了克服可能的伪遍历性问题，可以通过实现能量空间随机游走加速分子动力学模拟。为此，需要预先获得一个有偏自由能函数（BFEF）。尽管BFEF的质量对于采样效率至关重要，但其生成通常繁琐且不易。在这项工作中，我们提出了一种能量空间元动力学算法，以高效且稳健地获得BFEF。此外，为了处理由总能量空间中的随机游走引起的相关扩散采样问题，将原始伞形采样方法中的思想推广为在本质能量空间中的随机游走，该空间仅包括决定感兴趣区域构象的能量项。这种本质能量空间的推广允许实现高效的局部增强采样，并且当与目标事件无关的高频能量项未被激活时，还提供了进一步提高采样效率的可能性。在戊烷类系统、受阻丙氨酸二肽模型和亮氨酸模型的模拟中展示了用于分子动力学加速的能量空间元动力学方法及其在本质能量空间中的推广。
