Institute of Physical Chemistry, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany.
J Chem Phys. 2018 Aug 21;149(7):072328. doi: 10.1063/1.5027100.
We present a new concept of free energy calculations of chemical reactions by means of extended sampling molecular dynamics simulations. Biasing potentials are applied on partial atomic charges, which may be combined with atomic coordinates either in a single collective variable or in multi-dimensional biasing simulations. The necessary additional gradients are obtained by solving coupled-perturbed equations within the approximative density-functional tight-binding method. The new computational scheme was implemented in a combination of Gromacs and Plumed. As a prospective application, proton-coupled electron transfer in a model molecular system is studied. Two collective variables are introduced naturally, one for the proton transfer and the other for the electron transfer. The results are in qualitative agreement with the extended free simulations performed for reference. Free energy minima as well as the mechanism of the process are identified correctly, while the topology of the transition region and the height of the energy barrier are only reproduced qualitatively. The application also illustrates possible difficulties with the new methodology. These may be inefficient sampling of spatial coordinates when atomic charges are biased exclusively and a decreased stability of the simulations. Still, the new approach represents a viable alternative for free energy calculations of a certain class of chemical reactions, for instance a proton-coupled electron transfer in proteins.
我们提出了一种通过扩展采样分子动力学模拟计算化学反应自由能的新概念。偏置势应用于部分原子电荷，可以与原子坐标组合在单个集体变量或多维偏置模拟中。所需的附加梯度通过在近似密度泛函紧束缚方法内求解耦合微扰方程来获得。新的计算方案在 Gromacs 和 Plumed 的组合中实现。作为前瞻性应用，在模型分子系统中研究了质子耦合电子转移。引入了两个自然的集体变量，一个用于质子转移，另一个用于电子转移。结果与参考进行的扩展自由模拟定性一致。正确识别了自由能最小值以及过程的机制，而过渡区域的拓扑和能量势垒的高度仅定性再现。该应用还说明了新方法可能存在的困难。当仅偏置原子电荷时，空间坐标的采样效率可能较低，并且模拟的稳定性可能降低。尽管如此，对于某些类别的化学反应的自由能计算，例如蛋白质中的质子耦合电子转移，新方法代表了一种可行的替代方案。
