Zhang Haomiao, Gong Qiankun, Zhang Haozhe, Chen Changjun
Biomolecular Physics and Modeling Group, School of Physics, Huazhong University of Science and Technology, Wuhan 430074, Hubei, China.
J Comput Chem. 2019 Jul 30;40(20):1806-1815. doi: 10.1002/jcc.25834. Epub 2019 Apr 3.
Constructing a free energy landscape for a large molecule is difficult. One has to use either a high temperature or a strong driving force to enhance the sampling on the free energy barriers. In this work, we propose a mixed method that combines these two kinds of acceleration strategies into one simulation. First, it applies an adaptive biasing potential to some replicas of the molecule. These replicas are particularly accelerated in a collective variable space. Second, it places some unbiased and exchangeable replicas at various temperature levels. These replicas generate unbiased sampling data in the canonical ensemble. To improve the sampling efficiency, biased replicas transfer their state variables to the unbiased replicas after equilibrium by Monte Carlo trial moves. In comparison to previous integrated methods, it is more convenient for users. It does not need an initial reference biasing potential to guide the sampling of the molecule. And it is also unnecessary to insert many replicas for the requirement of passing the free energy barriers. The free energy calculation is accomplished in a single stage. It samples the data as fast as a biased simulation and it processes the data as simple as an unbiased simulation. The method provides a minimalist approach to the construction of the free energy landscape. © 2019 Wiley Periodicals, Inc.
构建大分子的自由能景观很困难。必须使用高温或强大的驱动力来增强在自由能壁垒上的采样。在这项工作中，我们提出了一种混合方法，将这两种加速策略结合到一个模拟中。首先，它对分子的一些副本应用自适应偏置势。这些副本在集体变量空间中得到特别加速。其次，它在不同温度水平放置一些无偏且可交换的副本。这些副本在正则系综中生成无偏采样数据。为了提高采样效率，有偏副本在平衡后通过蒙特卡罗试算移动将其状态变量转移到无偏副本。与以前的集成方法相比，它对用户更方便。它不需要初始参考偏置势来指导分子的采样。而且也无需为越过自由能壁垒的要求插入许多副本。自由能计算在单个阶段完成。它采样数据的速度与有偏模拟一样快，处理数据的方式与无偏模拟一样简单。该方法为构建自由能景观提供了一种极简方法。© 2019威利期刊公司。
