Wang Anhui, Zhang Zhichao, Li Guohui
Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics , Dalian Institute of Chemical Physics, Chinese Academy of Sciences , Dalian 116023 , China.
State Key Laboratory of Fine Chemicals, School of Chemistry , Dalian University of Technology , Dalian 116024 , China.
J Phys Chem Lett. 2018 Dec 20;9(24):7110-7116. doi: 10.1021/acs.jpclett.8b03471. Epub 2018 Dec 7.
The accuracy of molecular mechanics force fields is of vital importance in biomolecular simulations. However, the admittedly more accurate polarizable force fields were recently reported to be less able to reproduce the experimental properties in comparison to additive force fields in some cases. Here, we perform long-time-scale molecular dynamics simulations to systematically evaluate the effect of explicit electronic polarization in polarizable force fields. The results show that the inclusion of electrostatic polarization effect in polarizable force fields can improve their accuracies in protein structure refinement and generate conformational ensembles more approximate to experiments for intrinsically disordered proteins. In contrast, it is difficult for polarizable force fields to approach the native structure, let alone to predict the native state when it is unknown a priori in the real protein structure predictions. We speculate that these effects might be attributed to the preference of protein-water interactions in polarizable force fields.
分子力学力场的准确性在生物分子模拟中至关重要。然而，最近有报道称，在某些情况下，与加和力场相比，公认更精确的可极化力场在重现实验性质方面的能力较弱。在此，我们进行长时间尺度的分子动力学模拟，以系统评估可极化力场中显式电子极化的影响。结果表明，在可极化力场中纳入静电极化效应可以提高其在蛋白质结构优化方面的准确性，并为内在无序蛋白质生成更接近实验的构象集合。相比之下，在实际的蛋白质结构预测中，当天然状态先验未知时，可极化力场很难接近天然结构，更不用说预测天然状态了。我们推测，这些效应可能归因于可极化力场中蛋白质 - 水相互作用的偏好。
