The ff15ipq protein force field is a fixed charge model built by automated tools based on the two charge sets of the implicitly polarized charge method: one set (appropriate for vacuum) for deriving bonded parameters and the other (appropriate for aqueous solution) for running simulations. The duality is intended to treat water-induced electronic polarization with an understanding that fitting data for bonded parameters will come from quantum mechanical calculations in the gas phase. In this study, we compare ff15ipq to two alternatives produced with the same fitting software and a further expanded data set but following more conventional methods for tailoring bonded parameters (harmonic angle terms and torsion potentials) to the charge model. First, ff15ipq-Qsolv derives bonded parameters in the context of the ff15ipq solution phase charge set. Second, ff15ipq-Vac takes ff15ipq’s bonded parameters and runs simulations with the vacuum phase charge set used to derive those parameters. The IPolQ charge model and associated protocol for deriving bonded parameters are shown to be an incremental improvement over protocols that do not account for the material phases of each source of their fitting data. Both force fields incorporating the polarized charge set depict stable globular proteins and have varying degrees of success modeling the metastability of short (5–19 residues) peptides. In this particular case, ff15ipq-Qsolv increases stability in a number of $\alpha$-helices, correctly obtaining 70% helical character in the K19 system at 275 K and showing appropriately diminishing content up to 325 K, but overestimating the helical fraction of AAQAA₃ by 50% or more, forming long-lived $\alpha$-helices in simulations of a $\beta$-hairpin, and increasing the likelihood that the disordered p53 N-terminal peptide will also form a helix. This may indicate a systematic bias imparted by the ff15ipq-Qsolv parameter development strategy, which has the hallmarks of strategies used to develop other popular force fields, and may explain some of the need for manual corrections in this force fields’ evolution. In contrast, ff15ipq-Vac incorrectly depicts globular protein unfolding in numerous systems tested, including Trp cage, villin, lysozyme, and GB3, and does not perform any better than ff15ipq or ff15ipq-Qsolv in tests on short peptides. We analyze the free energy surfaces of individual amino acid dipeptides and the electrostatic potential energy surfaces of each charge model to explain the differences.

中文翻译：

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电荷模型与生物分子力场中键合参数力常数之间的联系

ff15ipq蛋白力场是由固定工具建立的固定电荷模型，该模型基于隐式极化电荷方法的两个电荷集：一组（适合真空）用于导出键合参数，另一组（适合水溶液）用于运行模拟。对偶性旨在处理水诱导的电子极化，同时要理解，用于键合参数的拟合数据将来自气相中的量子力学计算。在这项研究中，我们将ff15ipq与使用相同的拟合软件和进一步扩展的数据集但遵循更常规的方法将电荷参数（谐波角度项和扭转势）调整为电荷模型的两种替代方法进行比较。首先，ff15ipq- Qsolv在ff15ipq溶液相电荷集的背景下得出键合参数。其次，ff15ipq- Vac获取ff15ipq的键合参数，并使用真空相电荷集进行仿真，以得出这些参数。IPolQ收费模型和用于导出绑定参数的相关协议显示出相对于不考虑其拟合数据的每个源的材料阶段的协议的增量改进。包含极化电荷集的两个力场都描述了稳定的球状蛋白，并且成功地模拟了短肽（5–19个残基）的亚稳性。在这种特定情况下，ff15ipq- Qsolv可在以下几种情况下提高稳定性：$\alpha$-螺旋，可以在275 K时在K19系统中正确获得70％的螺旋特性，并显示适当降低的含量，直到325 K，但高估了AAQAA ₃的螺旋分数50％或更多，形成了长寿命的$\alpha$-a的模拟中的螺旋 $\beta$-发夹，并增加无序的p53 N末端肽也会形成螺旋的可能性。这可能表明ff15ipq- Qsolv参数开发策略赋予了系统性的偏见，它具有用于开发其他流行力场的策略的标志，并且可能解释了在此力场的演变过程中需要进行手动校正的某些情况。相比之下，ff15ipq- Vac错误地描述了在许多测试的系统中球形蛋白的展开，包括Trp笼，villin，溶菌酶和GB3，并且没有比ff15ipq或ff15ipq- Qsolv更好的表现在短肽测试中。我们分析了单个氨基酸二肽的自由能表面和每个电荷模型的静电势能表面，以解释差异。