Evaluating the Performance of Water Models with Host-Guest Force Fields in Binding Enthalpy Calculations for Cucurbit[7]uril-Guest Systems
Evaluating the Performance of Water Models with Host-Guest Force Fields in Binding Enthalpy Calculations for Cucurbit[7]uril-Guest Systems
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DOI：
10.1021/acs.jpcb.0c11383
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发表时间：
2021-02-04
影响因子：
3.3
通讯作者：
Biggin, Philip C.
中科院分区：
文献类型：
--
作者：
Cinaroglu, Suleyman Selim;Biggin, Philip C.
在计算机辅助药物设计中，用计算方法对热力学组分进行计算预测已变得越来越常规。尽管最近在自由能的计算方面有了很大的努力和改进，但对焓(和熵)的预测仍然没有得到充分的探索。此外，到目前为止，试图比较评估不同力场和水模型相互配合的情况的工作相对较少。在这里，我们报告了一个使用主-客体系统的力场和水模型的全面评估，该系统模仿了蛋白质-配体系统的许多特征。这些系统在计算上是便宜的，可能是因为与蛋白质配体系统相比，它们的体积很小。我们用多盒方法对一组25个瓜环-客体对进行了绝对热焓计算。考虑了8个水模型(TIP3P、TIP4P、TIP4P-EW、SPC、SPC/E、OPC、TIP5P、Bind3P)以及文献中常用的5个力场(GAFFv1、GAFFv2、CGenFF、Parsley和SwissParam)。我们观察到主客体结合热对力场和水模型的选择非常敏感。在水模型方面，我们发现TIP3P及其衍生模型Bind3P对于这一特定的主-客系统是性能最好的模型。脂肪族化合物的性能通常好于芳香族化合物，这表明在这些简单的力场中，芳香性仍然是一个很难准确包含的属性。
Computational prediction of thermodynamic components with computational methods has become increasingly routine in computer-aided drug design. Although there has been significant recent effort and improvements in the calculation of free energy, the prediction of enthalpy (and entropy) remains underexplored. Furthermore, there has been relatively little work reported so far that attempts to comparatively assess how well different force fields and water models perform in conjunction with each other. Here, we report a comprehensive assessment of force fields and water models using host-guest systems that mimic many features of protein-ligand systems. These systems are computationally inexpensive, possibly because of their small size compared to protein-ligand systems. We present absolute enthalpy calculations using the multibox approach on a set of 25 cucurbit[7]uril-guest pairs. Eight water models were considered (TIP3P, TIP4P, TIP4P-Ew, SPC, SPC/E, OPC, TIP5P, Bind3P), along with five force fields commonly used in the literature (GAFFv1, GAFFv2, CGenFF, Parsley, and SwissParam). We observe that host-guest binding enthalpies are strongly sensitive to the selection of force field and water model. In terms of water models, we find that TIP3P and its derivative Bind3P are the best performing models for this particular host-guest system. The performance is generally better for aliphatic compounds than for aromatic ones, suggesting that aromaticity remains a difficult property to include accurately in these simple force fields.