Department of Cell Biology, Microbiology and Molecular Biology , University of South Florida , Tampa , Florida 33620 , United States.
Physics and Materials Science Research Unit , University of Luxembourg , 162a avenue de la Fïancerie , Luxembourg City , L-1511 , Luxembourg.
J Chem Theory Comput. 2019 Apr 9;15(4):2444-2453. doi: 10.1021/acs.jctc.8b01198. Epub 2019 Mar 13.
Ion descriptors in molecular mechanics models are calibrated against reference data on ion-water interactions. It is then typically assumed that these descriptors will also satisfactorily describe interactions of ions with other functional groups, such as those present in biomolecules. However, several studies now demonstrate that this transferability assumption produces, in many different cases, large errors. Here we address this issue in a representative polarizable model and focus on transferability of cationic interactions from water to a series of alcohols. Both water and alcohols use hydroxyls for ion-coordination, and, therefore, this set of molecules constitutes the simplest possible case of transferability. We obtain gas phase reference data systematically from "gold-standard" quantum Monte Carlo and CCSD(T) methods, followed by benchmarked vdW-corrected DFT. We learn that the original polarizable model yields large gas phase water → alcohol transferability errors - the RMS and maximum errors are 2.3 and 5.1 kcal/mol, respectively. These errors are, nevertheless, systematic in that ion-alcohol interactions are overstabilized, and systematic errors typically imply that some essential physics is either missing or misrepresented. A comprehensive analysis shows that when both low- and high-field responses of ligand dipole polarization are described accurately, then transferability improves significantly - the RMS and maximum errors in the gas phase reduce, respectively, to 0.9 and 2.5 kcal/mol. Additionally, predictions of condensed phase transfer free energies also improve. Nevertheless, within the limits of the extrathermodynamic assumptions necessary to separate experimental estimates of salt dissolution into constituent cationic and anionic contributions, we note that the error in the condensed phase is systematic, which we attribute, at least, partially to the parametrization in long-range electrostatics. Overall, this work demonstrates a rational approach to boosting transferability of ionic interactions that will be applicable broadly to improving other polarizable and nonpolarizable models.
离子描述符在分子力学模型中是根据离子-水相互作用的参考数据进行校准的。通常假设这些描述符也可以满意地描述离子与其他官能团（如生物分子中的官能团）的相互作用。然而，现在有几项研究表明，这种可转移性假设在许多不同的情况下会产生很大的误差。在这里，我们在一个有代表性的极化模型中解决了这个问题，并专注于阳离子相互作用从水到一系列醇的转移。水和醇都使用羟基来进行离子配位，因此，这组分子构成了最简单的可转移情况。我们从“黄金标准”量子蒙特卡罗和 CCSD(T)方法系统地获得气相参考数据，然后进行经过基准测试的 vdW 修正 DFT。我们了解到原始的极化模型会导致很大的气相水→醇转移误差——均方根和最大误差分别为 2.3 和 5.1 kcal/mol。这些误差是系统的，因为离子-醇相互作用被过度稳定化，系统误差通常意味着一些基本物理要么缺失要么被错误地表示。综合分析表明，当准确描述配体偶极子极化的低场和高场响应时，转移性能会显著提高——气相中的均方根和最大误差分别降低到 0.9 和 2.5 kcal/mol。此外，预测的凝聚相转移自由能也有所提高。然而，在将盐溶解的实验估计值分离为组成阳离子和阴离子贡献所必需的外热力学假设的限制内，我们注意到凝聚相的误差是系统的，我们至少部分归因于长程静电的参数化。总的来说，这项工作展示了一种提高离子相互作用可转移性的合理方法，该方法将广泛适用于改进其他极化和非极化模型。
