Roe Daniel R, Bergonzo Christina, Cheatham Thomas E
Department of Medicinal Chemistry, College of Pharmacy, University of Utah , 2000 South 30 East Room 105, Salt Lake City, Utah 84112, United States.
J Phys Chem B. 2014 Apr 3;118(13):3543-52. doi: 10.1021/jp4125099. Epub 2014 Mar 25.
Many problems studied via molecular dynamics require accurate estimates of various thermodynamic properties, such as the free energies of different states of a system, which in turn requires well-converged sampling of the ensemble of possible structures. Enhanced sampling techniques are often applied to provide faster convergence than is possible with traditional molecular dynamics simulations. Hamiltonian replica exchange molecular dynamics (H-REMD) is a particularly attractive method, as it allows the incorporation of a variety of enhanced sampling techniques through modifications to the various Hamiltonians. In this work, we study the enhanced sampling of the RNA tetranucleotide r(GACC) provided by H-REMD combined with accelerated molecular dynamics (aMD), where a boosting potential is applied to torsions, and compare this to the enhanced sampling provided by H-REMD in which torsion potential barrier heights are scaled down to lower force constants. We show that H-REMD and multidimensional REMD (M-REMD) combined with aMD does indeed enhance sampling for r(GACC), and that the addition of the temperature dimension in the M-REMD simulations is necessary to efficiently sample rare conformations. Interestingly, we find that the rate of convergence can be improved in a single H-REMD dimension by simply increasing the number of replicas from 8 to 24 without increasing the maximum level of bias. The results also indicate that factors beyond replica spacing, such as round trip times and time spent at each replica, must be considered in order to achieve optimal sampling efficiency.
通过分子动力学研究的许多问题都需要准确估计各种热力学性质，例如系统不同状态的自由能，这反过来又需要对可能结构的系综进行充分收敛的采样。增强采样技术经常被应用，以提供比传统分子动力学模拟更快的收敛速度。哈密顿副本交换分子动力学（H-REMD）是一种特别有吸引力的方法，因为它允许通过对各种哈密顿量进行修改来纳入多种增强采样技术。在这项工作中，我们研究了H-REMD与加速分子动力学（aMD）相结合对RNA四核苷酸r(GACC)的增强采样，其中对扭转施加了增强势，并将其与H-REMD提供的增强采样进行比较，在H-REMD中扭转势垒高度被缩放到更低的力常数。我们表明，H-REMD和多维REMD（M-REMD）与aMD相结合确实增强了对r(GACC)的采样，并且在M-REMD模拟中添加温度维度对于有效采样稀有构象是必要的。有趣的是，我们发现通过简单地将副本数量从8增加到24而不增加最大偏差水平，可以在单个H-REMD维度中提高收敛速度。结果还表明，为了实现最佳采样效率，必须考虑除副本间距之外的因素，例如往返时间和在每个副本上花费的时间。
