Constant-pH Hybrid Nonequilibrium Molecular Dynamics Monte Carlo Simulation Method
Constant-pH Hybrid Nonequilibrium Molecular Dynamics Monte Carlo Simulation Method
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DOI：
10.1021/acs.jctc.5b00261
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发表时间：
2015-08-01
影响因子：
5.5
通讯作者：
Roux, Benoit
中科院分区：
文献类型：
--
作者：
Chen, Yunjie;Roux, Benoit
本文开发了一种计算方法，用于在恒定ph条件下对复杂分子体系进行显式溶剂模拟。在恒定ph模拟中，预先确定的可电离位点可以根据环境和施加的ph作为时间的函数自发地进行质子化和去质子化。物理学报，2007,126,164112)，包括执行短的非平衡分子动力学（neMD）开关轨迹，以产生具有改变质子状态的物理上合理的构型，这些构型随后根据Metropolis蒙特卡罗（MC）标准被接受或拒绝。为了保证这种非平衡开关产生的微观细节平衡，原子动量根据对称的两端动量反转处方被改变。为了获得更高的效率，原始neMD-MC方案被分成两个步骤，减少了生成大量非生产性和昂贵的非平衡轨迹的需要。在第一步中，根据固有的pK(a)，通过Metropolis MC过程随机地确定一个位点的质子化状态；只有当质子化状态的这种变化被接受时，才会产生一个尝试的非平衡开关。该方法采用两步固有pK(a) neMD-MC模拟方法，以单氨基酸（Asp、Glu和His）为测试对象，并应用于火鸡卵样黏液第三结构域和蛋清溶菌酶。由于计算成本相对于可滴定位点的数量呈简单的线性增长，因此本方法自然能够处理非常大的系统。
A computational method is developed to carry out explicit solvent simulations of complex molecular systems under conditions of constant pH. In constant-pH simulations, preidentified ionizable sites are allowed to spontaneously protonate and deprotonate as a function of time in response to the environment and the imposed pH. The method, based on a hybrid scheme originally proposed by H. A. Stern (J. Chem. Phys. 2007, 126, 164112), consists of carrying out short nonequilibrium molecular dynamics (neMD) switching trajectories to generate physically plausible configurations with changed protonation states that are subsequently accepted or rejected according to a Metropolis Monte Carlo (MC) criterion. To ensure microscopic detailed balance arising from such nonequilibrium switches, the atomic momenta are altered according to the symmetric two-ends momentum reversal prescription. To achieve higher efficiency, the original neMD-MC scheme is separated into two steps, reducing the need for generating a large number of unproductive and costly nonequilibrium trajectories. In the first step, the protonation state of a site is randomly attributed via a Metropolis MC process on the basis of an intrinsic pK(a); an attempted nonequilibrium switch is generated only if this change in protonation state is accepted. This hybrid two-step inherent pK(a) neMD-MC simulation method is tested with single amino acids in solution (Asp, Glu, and His) and then applied to turkey ovomucoid third domain and hen egg-white lysozyme. Because of the simple linear increase in the computational cost relative to the number of titratable sites, the present method is naturally able to treat extremely large systems.