Department of Chemistry , University of Florida , Gainesville , Florida 32611 , United States.
J Chem Theory Comput. 2019 Feb 12;15(2):871-881. doi: 10.1021/acs.jctc.8b00935. Epub 2019 Jan 18.
Efficient computational methods that are capable of supporting experimental measures obtained at constant values of pH and redox potential are important tools as they serve to, among other things, provide additional atomic level information that cannot be obtained experimentally. Replica Exchange is an enhanced sampling technique that allows converged results to be obtained faster in comparison to regular molecular dynamics simulations. In this work we report the implementation, also available with GPU-accelerated code, of pH and redox potential (E) as options for multidimensional REMD simulations in AMBER. Previous publications have only reported multidimensional REMD simulations with the temperature and Hamiltonian dimensions. In this work results are shown for N-acetylmicroperoxidase-8 (NAcMP8) axially attached to a histidine peptide. This is a small system that contains only a single heme group. We compare results from E,pH-REMD, E,T-REMD, and E,T,pH-REMD to one-dimensional REMD simulations and to simulations without REMD. We show that two-dimensional REMD simulations improve sampling convergence in comparison to one-dimensional REMD simulations and that three-dimensional REMD further improves convergence in comparison to two-dimensional REMD simulations. Also, our computational benchmarks show that our multidimensional REMD calculations have a small and bearable computational performance, essentially the same as one-dimensional REMD. However, multidimensional REMD makes use of a significantly higher number of replicas because the number of replicas scales geometrically with the number of dimensions; therefore, more computational resources are required. In addition to the pH dependence on standard redox potential values and the redox potential dependence on p K values, we also investigate the influence of the temperature in our results. We observe an agreement between our computational results and purely theoretical predictions.
高效的计算方法能够支持在恒定 pH 值和氧化还原电位条件下获得的实验测量，这是一种重要的工具，因为它可以提供无法通过实验获得的额外原子水平信息。复制交换是一种增强采样技术，与常规分子动力学模拟相比，可以更快地获得收敛结果。在这项工作中，我们报告了在 AMBER 中实现 pH 值和氧化还原电位（E）作为多维 REMD 模拟选项的情况，也提供了 GPU 加速代码。以前的出版物仅报告了具有温度和哈密顿维度的多维 REMD 模拟。在这项工作中，展示了轴向附着在组氨酸肽上的 N-乙酰基微过氧化物酶-8（NAcMP8）的结果。这是一个包含单个血红素基团的小系统。我们将 E,pH-REMD、E,T-REMD 和 E,T,pH-REMD 的结果与一维 REMD 模拟和没有 REMD 的模拟进行了比较。我们表明，二维 REMD 模拟比一维 REMD 模拟改善了采样收敛性，而三维 REMD 模拟进一步提高了与二维 REMD 模拟的收敛性。此外，我们的计算基准表明，我们的多维 REMD 计算具有较小且可承受的计算性能，基本上与一维 REMD 相同。然而，多维 REMD 利用了更高数量的副本，因为副本数量与维度数量呈几何级数增长；因此，需要更多的计算资源。除了标准氧化还原电位值对 pH 值的依赖性和 pK 值对氧化还原电位的依赖性外，我们还研究了温度对我们结果的影响。我们观察到我们的计算结果与纯粹的理论预测之间的一致性。
