Departments of Molecular Biology and Biochemistry, Chemical and Biomolecular Engineering, Materials Science and Engineering, and Biomedical Engineering, University of California, Irvine, Irvine, California92697, United States.
SBP Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California92037, United States.
J Chem Theory Comput. 2022 Oct 11;18(10):6172-6188. doi: 10.1021/acs.jctc.2c00710. Epub 2022 Sep 12.
A key advantage of polarizable force fields is their ability to model the atomic polarization effects that play key roles in the atomic many-body interactions. In this work, we assessed the accuracy of the recently developed polarizable Gaussian Multipole (pGM) models in reproducing quantum mechanical (QM) interaction energies, many-body interaction energies, as well as the nonadditive and additive contributions to the many-body interactions for peptide main-chain hydrogen-bonding conformers, using glycine dipeptide oligomers as the model systems. Two types of pGM models were considered, including that with (pGM-perm) and without (pGM-ind) permanent atomic dipoles. The performances of the pGM models were compared with several widely used force fields, including two polarizable (Amoeba13 and ff12pol) and three additive (ff19SB, ff15ipq, and ff03) force fields. Encouragingly, the pGM models outperform all other force fields in terms of reproducing QM interaction energies, many-body interaction energies, as well as the nonadditive and additive contributions to the many-body interactions, as measured by the root-mean-square errors (RMSEs) and mean absolute errors (MAEs). Furthermore, we tested the robustness of the pGM models against polarizability parameterization errors by employing alternative polarizabilities that are either scaled or obtained from other force fields. The results show that the pGM models with alternative polarizabilities exhibit improved accuracy in reproducing QM many-body interaction energies as well as the nonadditive and additive contributions compared with other polarizable force fields, suggesting that the pGM models are robust against the errors in polarizability parameterizations. This work shows that the pGM models are capable of accurately modeling polarization effects and have the potential to serve as templates for developing next-generation polarizable force fields for modeling various biological systems.
各向异性极化力场的一个主要优势在于它们能够模拟在原子多体相互作用中起关键作用的原子极化效应。在这项工作中，我们使用甘氨酸二肽寡聚物作为模型系统，评估了最近开发的极化高斯多极（pGM）模型在再现量子力学（QM）相互作用能、多体相互作用能以及肽主链氢键构象中非加和和加和对多体相互作用的贡献方面的准确性。考虑了两种类型的 pGM 模型，包括带有（pGM-perm）和不带有（pGM-ind）永久原子偶极子的模型。将 pGM 模型的性能与几种广泛使用的力场进行了比较，包括两种极化（Amoeba13 和 ff12pol）和三种加和（ff19SB、ff15ipq 和 ff03）力场。令人鼓舞的是，pGM 模型在再现 QM 相互作用能、多体相互作用能以及非加和和加和对多体相互作用的贡献方面均优于所有其他力场，这可以通过均方根误差（RMSE）和平均绝对误差（MAE）来衡量。此外，我们通过使用要么缩放要么从其他力场获得的替代极化率来测试 pGM 模型对极化率参数化错误的稳健性。结果表明，与其他极化力场相比，具有替代极化率的 pGM 模型在再现 QM 多体相互作用能以及非加和和加和贡献方面表现出更高的准确性，这表明 pGM 模型对极化率参数化错误具有稳健性。这项工作表明，pGM 模型能够准确地模拟极化效应，并有可能作为开发用于模拟各种生物系统的下一代极化力场的模板。
