Calculation of the free energy of polarization: quantifying the effect of explicitly treating electronic polarization on the transferability of force-field parameters.
Calculation of the free energy of polarization: quantifying the effect of explicitly treating electronic polarization on the transferability of force-field parameters.
复制标题
极化自由能的计算：量化明确处理电子极化对力场参数可传递性的影响。
DOI：
10.1021/jp0706477
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
W. V. van Gunsteren
中科院分区：
文献类型：
--
作者：
D. Geerke;W. V. van Gunsteren
在nonpolarizable力场中的电子极化的缺乏一个明确的描述通常会导致力场参数集的不完整的transferability时，在极地或非极地环境中的感兴趣的系统的模拟应用。例如，使用优化的nonpolarizable参数集再现实验数据的性质的纯液体的极性化合物通常产生太低的溶解度在水中的相应的化合物。原因在于，对于纯液体校准的固定电荷分布在水合的情况下可能对应于过低的分子偶极矩。在目前的研究中，我们定量地表明，明确包括电子极化可以提高生物分子力场参数集的可转移性。有了这个目的，自由能的极化，DeltaGpola，已计算出，与DeltaGpola对应的自由能差相同的系统所描述的极化和nonpolarizable模型。使用一个nonpolarizable模型和一个polarizable一个（基于弹簧上的电荷的方法）的二甲醚（DME），这两个参数化再现纯液体性质的实验值，小的值被发现为DeltaGpola的纯液体或当DME溶质溶剂化在非极性溶剂环己烷。然而，对于在水中水合的溶质，DeltaGpola被发现是相同的数量级之间的差异，从模拟使用nonpolarizable溶质模型和实验值的水合自由能。因此，引入极化率明显提高了参数集的可传递性。此外，在计算溶剂化在DME中的阴离子时，溶剂的DeltaGpola采用了相对较大的值。从计算的自由能差异的误差估计，它进一步表明，DeltaGpola的计算提供了一个有效的和准确的方法来获得由极化和nonpolarizable模型描述的系统之间的溶剂化（或过剩）自由能的差异相比，溶剂化（或过剩）自由能的直接计算。
The lack of an explicit description of electronic polarization in nonpolarizable force fields usually results in an incomplete transferability of force-field parameter sets when applied in simulations of the system of interest in either a polar or an apolar environment. For example, the use of nonpolarizable parameter sets optimized to reproduce experimental data on properties of pure liquids of polar compounds commonly yields too low solubilities in water for the corresponding compounds. The reason is that the fixed charge distributions calibrated for the pure liquid might correspond to too low molecular dipole moments in case of hydration. In the current study, we quantitatively show that explicit inclusion of electronic polarization can improve the transferability of biomolecular force-field parameter sets. With this aim, free energies of polarization, DeltaGpola, have been calculated, with DeltaGpola corresponding to the free energy difference between identical systems described by a polarizable and a nonpolarizable model. Using a nonpolarizable model and a polarizable one (based on the charge-on-spring approach) for dimethyl ether (DME), which were both parametrized to reproduce experimental values for pure liquid properties, small values were found for DeltaGpola for the pure liquid or when a DME solute was solvated in the apolar solvent cyclohexane. For the solute hydrated in water, however, DeltaGpola was found to be of the same order of magnitude as the discrepancy between the free energy of hydration from simulation using a nonpolarizable solute model and the experimental value. Thus, introducing polarizabilities clearly improves the transferability of the parameter set. Additionally, in calculations of an anion solvated in DME, DeltaGpola for the solvent adopted relatively large values. From an estimation of the errors in the calculated free energy differences, it was furthermore shown that the calculation of DeltaGpola offers an effective and accurate method to obtain differences in solvation (or excess) free energies between systems described by polarizable and nonpolarizable models when compared to a direct calculation of solvation (or excess) free energies.