Redox potential replica exchange molecular dynamics at constant pH in AMBER: implementation and validation
Redox potential replica exchange molecular dynamics at constant pH in AMBER: implementation and validation
复制标题
DOI：
10.1063/1.5027379
复制
发表时间：
2018-08-21
影响因子：
4.4
通讯作者：
Roitberg, Adrian E.
中科院分区：
文献类型：
--
作者：
Cruzeiro, Vinicius Wilian D.;Amaral, Marcos S.;Roitberg, Adrian E.
氧化还原过程在化学中很重要，在生物医学、化学分析等方面有应用。由于许多氧化还原实验也在固定的pH值下进行，因此具有有效的计算方法来支持恒定氧化还原电位和pH下的实验测量是非常重要的。这样的计算技术有可能验证在这些条件下进行的实验观察，并提供额外的信息无法实现的实验，如原子水平的宏观措施的描述。我们目前的实现离散氧化还原和质子化状态的方法恒定氧化还原电位分子动力学（CEMD），耦合恒定pH和恒定氧化还原电位MD（C（pH，E）MD），和E-REMD交换MD沿着氧化还原电位的尺寸（E-REMD）的AMBER软件包。验证结果是一个小的系统，包含一个单一的血红素组：N-乙酰微过氧化物酶-8（NAcMP 8）轴向连接到一个组氨酸肽。所实施的方法允许人们使用目前在AMBER上可用的恒定pH分子动力学和pH-REMD方法进行标准氧化还原电位（E度）预测，其简单性和准确性与pK（a）预测相同。在我们的模拟中，我们可以正确地描述，也与理论预测一致，以下行为：当氧化还原活性基团被还原时，接近pH活性基团的pK（a）增加，因为它变得更容易附着质子;同样，当pH活性基团被质子化时，相邻氧化还原活性基团的标准氧化还原电位（E度）上升。此外，我们的研究结果还表明，E-REMD是能够实现更快的统计收敛比CEMD或C（pH，E）MD。此外，使用我们的方法的计算基准显示GPU（图形处理单元）加速计算的高性能相比，传统的CPU（中央处理单元）计算。出版社：AIP Publishing
Redox processes are important in chemistry, with applications in biomedicine, chemical analysis, among others. As many redox experiments are also performed at a fixed value of pH, having an efficient computational method to support experimental measures at both constant redox potential and pH is very important. Such computational techniques have the potential to validate experimental observations performed under these conditions and to provide additional information unachievable experimentally such as an atomic level description of macroscopic measures. We present the implementation of discrete redox and protonation states methods for constant redox potential Molecular Dynamics (CEMD), for coupled constant pH and constant redox potential MD (C(pH,E)MD), and for Replica Exchange MD along the redox potential dimension (E-REMD) on the AMBER software package. Validation results are presented for a small system that contains a single heme group: N-acetylmicroperoxidase-8 (NAcMP8) axially connected to a histidine peptide. The methods implemented allow one to make standard redox potential (E degrees) predictions with the same easiness and accuracy as pK(a )predictions using the constant pH molecular dynamics and pH-REMD methods currently available on AMBER. In our simulations, we can correctly describe, in agreement also with theoretical predictions, the following behaviors: when a redox-active group is reduced, the pK(a) of a near pH-active group increases because it becomes easier for a proton to be attached; equivalently, when a pH-active group is protonated, the standard redox potential (E degrees) of an adjacent redox-active group rises. Furthermore, our results also show that E-REMD is able to achieve faster statistical convergence than CEMD or C(pH,E)MD. Moreover, computational benchmarks using our methodologies show high-performance of GPU (Graphics Processing Unit) accelerated calculations in comparison to conventional CPU (Central Processing Unit) calculations. Published by AIP Publishing.