Department of Physics and Earth Sciences, Jacobs University Bremen, 28759 Bremen, Germany.
Department of Life Sciences and Chemistry, Jacobs University Bremen, 28759 Bremen, Germany.
J Chem Inf Model. 2020 Jun 22;60(6):3188-3203. doi: 10.1021/acs.jcim.0c00389. Epub 2020 Jun 15.
In the past two decades, molecular dynamics simulations have become the method of choice for elucidating the transport mechanisms of ions through various membrane channels. Often, these simulations heavily rely on classical nonpolarizable force fields (FFs), which lack electronic polarizability in the treatment of the electrostatics. The recent advancements in the Drude polarizable FF lead to a complete set of parameters for water, ions, protein, and lipids, allowing for a more realistic modeling of membrane proteins. However, the quality of these Drude FFs remains untested for such systems. Here, we examine the quality of this FF set in two ways, i.e., (i) in simple ionic aqueous solution simulations and (ii) in more complex membrane channel simulations. First, the aqueous solutions of KCl, NaCl, MgCl, and CaCl salts are simulated using the polarizable Drude and the nonpolarizable CHARMM36 FFs. The bulk conductivity has been estimated for both FF sets using applied-field simulations for several concentrations and temperatures in the case of all investigated salts and compared to experimental findings. An excellent improvement in the ability of the Drude FF to reproduce the experimental bulk conductivities for KCl, NaCl, and MgCl solutions can be observed but not in the case of CaCl. Moreover, the outer membrane channel OmpC from the bacterium has been employed to examine the ability of the polarizable and nonpolarizable FFs to reproduce ion transport-related quantities known from experiment. Unbiased and applied-field simulations have been performed in the presence of KCl using both FF sets. Unlike for the bulk systems of aqueous salt solutions, it has been found that the Drude FF is not accurate in modeling KCl transport properties across the OmpC porin.
在过去的二十年中，分子动力学模拟已成为阐明各种膜通道中离子传输机制的首选方法。通常，这些模拟严重依赖于经典的非极化力场（FF），在处理静电时缺乏电子极化率。最近在 Drude 极化 FF 方面的进展导致了一套完整的参数，用于水、离子、蛋白质和脂质，从而可以更真实地模拟膜蛋白。然而，这些 Drude FF 对于此类系统的质量仍未经过测试。在这里，我们通过两种方式检查了这个 FF 集的质量，即（i）在简单的离子水溶液模拟中和（ii）在更复杂的膜通道模拟中。首先，使用极化的 Drude 和非极化的 CHARMM36 FF 模拟了 KCl、NaCl、MgCl 和 CaCl 盐的水溶液。对于所有研究的盐，使用施加场模拟在几种浓度和温度下估算了这两个 FF 集的体电导率，并与实验结果进行了比较。可以观察到 Drude FF 能够显著提高对 KCl、NaCl 和 MgCl 溶液实验体电导率的再现能力，但对 CaCl 则不然。此外，还使用了来自细菌的外膜通道 OmpC 来检查极化和非极化 FF 再现实验中已知的离子传输相关量的能力。在存在 KCl 的情况下，使用这两个 FF 集进行了无偏和施加场模拟。与水溶液盐的体系统不同，发现 Drude FF 在模拟 OmpC 孔道中 KCl 的传输性质方面不够准确。
