Born-Oppenheimer Ab Initio QM/MM Molecular Dynamics Simulations of Enzyme Reactions.
Born-Oppenheimer Ab Initio QM/MM Molecular Dynamics Simulations of Enzyme Reactions.
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DOI：
10.1016/bs.mie.2016.05.013
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发表时间：
2016
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Zhou Y;Wang S;Li Y;Zhang Y
可靠地模拟酶反应有两个关键要求：一个是合理准确的势能面，以描述键形成/断裂过程以及充分模拟异质酶环境;另一个是进行广泛的采样，因为酶系统由至少数千个原子组成，其能量景观非常复杂。一个有吸引力的方法，以满足这两个艰巨的任务是Born-Oppenheimer从头算QM/MM分子动力学模拟（aiQM/MM-MD）与伞采样。在这一章中，我们描述了我们最近开发的赝键Q-Chem-Amber界面，它采用了结合静电-机械嵌入方案与周期性边界条件和粒子网格Ewald方法的远程静电相互作用。在我们的实现中，Q-Chem和Amber的打磨模块在源代码级别结合在一起，而不使用系统调用，QM和MM计算之间的所有必要数据通信都是通过计算机内存实现的。我们证明了这种pseudobond Q-Chem-Amber接口的适用性，提出了两个例子，一个反应在水溶液中，一个酶反应。最后，我们描述了我们建立的aiQM/MM-MD酶模拟协议，该协议已成功地应用于研究十几种酶。
There are two key requirements for reliably simulating enzyme reactions: one is a reasonably accurate potential energy surface to describe the bond forming/breaking process as well as to adequately model the heterogeneous enzyme environment; the other is to perform extensive sampling since an enzyme system consists of at least thousands of atoms and its energy landscape is very complex. One attractive approach to meet both daunting tasks is Born-Oppenheimer ab initio QM/MM molecular dynamics simulation (aiQM/MM-MD) with umbrella sampling. In this chapter, we describe our recently developed pseudobond Q-Chem–Amber interface, which employs a combined electrostatic-mechanical embedding scheme with periodic boundary condition and the particle mesh Ewald method for long-range electrostatics interactions. In our implementation, Q-Chem and the sander module of Amber are combined at the source code level without using system calls, and all necessary data communications between QM and MM calculations are achieved via computer memory. We demonstrate the applicability of this pseudobond Q-Chem–Amber interface by presenting two examples, one reaction in aqueous solution and one enzyme reaction. Finally, we describe our established aiQM/MM-MD enzyme simulation protocol, which has been successfully applied to study more than a dozen enzymes.