Toward Automated Benchmarking of Atomistic Force Fields: Neat Liquid Densities and Static Dielectric Constants from the ThermoML Data Archive
Toward Automated Benchmarking of Atomistic Force Fields: Neat Liquid Densities and Static Dielectric Constants from the ThermoML Data Archive
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DOI：
10.1021/acs.jpcb.5b06703
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发表时间：
2015-10-08
影响因子：
3.3
通讯作者：
Chodera, John D.
中科院分区：
文献类型：
--
作者：
Beauchamp, Kyle A.;Behr, Julie M.;Chodera, John D.
原子分子模拟是进行定量预测的有力方法，但这些预测的准确性完全取决于所使用的力场的质量。尽管对基本物理性质的实验测量为评估力场质量提供了一种直接的方法，但这些信息的大部分都是以机器不可读的格式捆绑在一起的。从非机器可读的源编译物理属性的基准数据集需要大量的人力，并且容易积累人为错误，从而阻碍了可重复的力场精度基准的开发。在这里，我们研究了针对NIST的物理化学测量的温度计数据档案的原子力场基准测试的可行性，该档案以便携式，机器可读，自注释的iupac标准格式汇总了数千个实验测量。作为概念证明，我们使用AM1-BCC电荷模型对从档案中自动提取的实验测量（特别是体积液体密度和环境压力下的静态介电常数）提出了广义琥珀小分子力场（GAFF）的详细基准，并讨论了可用于更大规模（或连续执行）基准的数据范围。即使这个有限的初始基准的结果也突出了低介电环境中固定电荷力场的普遍问题，例如在结合腔或生物膜中看到的那些。
Atomistic molecular simulations are a powerful way to make quantitative predictions, but the accuracy of these predictions depends entirely on the quality of the force field employed. Although experimental measurements of fundamental physical 0 properties offer a straightforward approach for evaluating force field quality, the bulk of this information has been tied up in formats that are not machine-readable. Compiling benchmark data sets of physical properties from non-machine-readable sources requires substantial human effort and is prone to the accumulation of human errors, hindering the development of reproducible benchmarks of force-field accuracy. Here, we examine the feasibility of benchmarking atomistic force fields against the NIST ThermoML data archive of physicochemical measurements, which aggregates thousands of experimental measurements in a portable, machine-readable, self-annotating IUPAC-standard format. As a proof of concept, we present a detailed benchmark of the generalized Amber small-molecule force field (GAFF) using the AM1-BCC charge model against experimental measurements (specifically, bulk liquid densities and static dielectric constants at ambient pressure) automatically extracted from the archive and discuss the extent of data available for use in larger scale (or continuously performed) benchmarks. The results of even this limited initial benchmark highlight a general problem with fixed-charge force fields in the representation low-dielectric environments, such as those seen in binding cavities or biological membranes.