Constant pH Molecular Dynamics in Explicit Solvent with Enveloping Distribution Sampling and Hamiltonian Exchange.
Constant pH Molecular Dynamics in Explicit Solvent with Enveloping Distribution Sampling and Hamiltonian Exchange.
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DOI：
10.1021/ct500175m
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发表时间：
2014-07-08
影响因子：
5.5
通讯作者：
Brooks, Bernard R.
中科院分区：
文献类型：
--
作者：
Lee, Juyong;Miller, Benjamin T.;Damjanovic, Ana;Brooks, Bernard R.
提出了一种基于包络分布抽样(EDS)和哈密顿副本交换(HREX)相结合的显式溶剂中恒定pH模拟的新方法。与基于可变电荷模型和连续电荷模型的恒定pH方法不同，我们的方法是基于离散质子化状态。EDS产生不同质子化状态的混合哈密顿量。使用光滑度参数S来控制混合状态能源景观的能量屏障高度。较小的S值可通过降低能量壁垒来促进状态转换。具有不同S值的EDS势之间的副本交换允许我们很容易地获得具有频繁态转变的多质子化态的热力学精确系综。分析是用从未经平滑的能谱哈密顿量得到的系综S=∞进行的，它严格遵循端态的最小能面。对天冬氨酸、赖氨酸和谷氨酸两种质子化状态、三种状态的组氨酸、四种状态的四个残基和八种状态的蛇心毒素进行了检测，验证了该方法的准确性和有效性。用EDS-HREX方法估算的pKa值与实验pKa值吻合较好。小型基准系统的平均绝对误差在0.03~0.17pkA单位之间，蛇心毒素三个可滴定组的平均绝对误差在0.2~1.6pkA单位之间。这项研究表明，EDS-HREX是一个有效的理论框架，它正确地描述了多个质子态，并计算了良好的pKa值。
We present a new computational approach for constant pH simulations in explicit solvent based on the combination of the enveloping distribution sampling (EDS) and Hamiltonian replica exchange (HREX) methods. Unlike constant pH methods based on variable and continuous charge models, our method is based on discrete protonation states. EDS generates a hybrid Hamiltonian of different protonation states. A smoothness parameter s is used to control the heights of energy barriers of the hybrid-state energy landscape. A small s value facilitates state transitions by lowering energy barriers. Replica exchange between EDS potentials with different s values allows us to readily obtain a thermodynamically accurate ensemble of multiple protonation states with frequent state transitions. The analysis is performed with an ensemble obtained from an EDS Hamiltonian without smoothing, s = ∞, which strictly follows the minimum energy surface of the end states. The accuracy and efficiency of this method is tested on aspartic acid, lysine, and glutamic acid, which have two protonation states, a histidine with three states, a four-residue peptide with four states, and snake cardiotoxin with eight states. The pKa values estimated with the EDS-HREX method agree well with the experimental pKa values. The mean absolute errors of small benchmark systems range from 0.03 to 0.17 pKa units, and those of three titratable groups of snake cardiotoxin range from 0.2 to 1.6 pKa units. This study demonstrates that EDS-HREX is a potent theoretical framework, which gives the correct description of multiple protonation states and good calculated pKa values.
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影响因子：
4.1
作者：
BENNETT, CH
通讯作者：
BENNETT, CH
影响因子：
4.4
作者：
Chu, JW;Trout, BL;Brooks, BR
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ANDERSON, DE;BECKTEL, WJ;DAHLQUIST, FW
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4.4
作者：
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van Gunsteren, Wilfred F.
影响因子：
4.4
作者：
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通讯作者：
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