Department of Biological Sciences, Chemistry, Bioengineering, and Computer Science and Engineering, Lehigh University, Bethlehem, Pennsylvania 18015, United States.
Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas 76019-9800, United States.
J Chem Theory Comput. 2024 Jun 25;20(12):5337-5351. doi: 10.1021/acs.jctc.4c00439. Epub 2024 Jun 10.
Quantum mechanical (QM) treatments, when combined with molecular mechanical (MM) force fields, can effectively handle enzyme-catalyzed reactions without significantly increasing the computational cost. In this context, we present CHARMM-GUI , a web-based cyberinfrastructure designed to streamline the preparation of various QM/MM simulation inputs with ligand modification. The development of has been achieved through integration with existing CHARMM-GUI modules, such as , , and . In addition, new functionalities have been developed to facilitate the one-stop preparation of QM/MM systems and enable interactive and intuitive ligand modifications and QM atom selections. offers support for a range of semiempirical QM methods, including AM1(+/d), PM3(+/PDDG), MNDO(+/d, +/PDDG), PM6, RM1, and SCC-DFTB, tailored for both AMBER and CHARMM. A nontrivial setup related to ligand modification, link-atom insertion, and charge distribution is automatized through intuitive user interfaces. To illustrate the robustness of , we conducted QM/MM simulations of three enzyme-substrate systems: dihydrofolate reductase, insulin receptor kinase, and oligosaccharyltransferase. In addition, we have created three tutorial videos about building these systems, which can be found at https://www.charmm-gui.org/demo/qmi. is expected to be a valuable and accessible web-based tool that simplifies and accelerates the setup process for hybrid QM/MM simulations.
量子力学（QM）处理方法与分子力学（MM）力场相结合，可以有效地处理酶催化反应，而不会显著增加计算成本。在这种情况下，我们提出了 CHARMM-GUI，这是一个基于网络的网络基础设施，旨在简化具有配体修饰的各种 QM/MM 模拟输入的准备工作。的开发是通过与现有的 CHARMM-GUI 模块（如 ， ，和 ）集成实现的。此外，还开发了新的功能，以方便一站式准备 QM/MM 系统，并实现交互式和直观的配体修饰和 QM 原子选择。提供了一系列半经验 QM 方法的支持，包括 AM1(+/d)、PM3(+/PDDG)、MNDO(+/d, +/PDDG)、PM6、RM1 和 SCC-DFTB，适用于 AMBER 和 CHARMM。通过直观的用户界面，自动处理配体修饰、链接原子插入和电荷分布等复杂设置。为了说明的稳健性，我们对三个酶-底物系统进行了 QM/MM 模拟：二氢叶酸还原酶、胰岛素受体激酶和寡糖基转移酶。此外，我们还创建了三个关于构建这些系统的教程视频，可以在 https://www.charmm-gui.org/demo/qmi 上找到。预计将成为一个有价值的、易于访问的基于网络的工具，简化和加速混合 QM/MM 模拟的设置过程。
