Evaluation of Representations and Response Models for Polarizable Force Fields.

For classical simulations of condensed-phase systems, such as organic liquids and biomolecules, to achieve high accuracy, they will probably need to incorporate an accurate, efficient model of conformation-dependent electronic polarization. Thus, it is of interest to understand what determines the accuracy of a polarizable electrostatics model. This study approaches this problem by breaking polarization models down into two main components: the representation of electronic polarization and the response model used for mapping from an inducing field to the polarization within the chosen representation. Among the most common polarization representations are redistribution of atom-centered charges, such as those used in the fluctuating charge model, and atom-centered point dipoles, such as those used in a number of different polarization models. Each of these representations has been combined with one or more response models. The response model of fluctuating charge, for example, is based on the idea of electronegativity equalization in the context of changing electrostatic potentials (ESPs), whereas point-dipole representations typically use a response model based on point polarizabilities whose induced dipoles are computed based on interaction with other charges and dipoles. Here, we decouple polarization representations from their typical response models to analyze the strengths and weaknesses of various polarization approximations. First, we compare the maximal possible accuracies achievable by the charge redistribution and point-dipole model representations, by testing their ability to replicate quantum mechanical (QM) ESPs around small molecules polarized by external inducing charges. Perhaps not surprisingly, the atom-centered dipole model can yield higher accuracy. Next, we test two of the most commonly used response functions used for the point-dipole representations, self-consistent and direct (or first-order) inducible point polarizabilities, where the polarizabilities are optimized to best fit the full set of polarized QM potentials for each molecule studied. Strikingly, the induced-dipole response model markedly degrades accuracy relative to that obtainable with optimal point dipoles. In fact, the maximal accuracy achievable with this response model is even lower than that afforded by an optimal charge-redistribution representation. This means that, if coupled with a sufficiently accurate response function, the point-charge representation could outperform the standard induced-dipole model. Furthermore, although a key advantage of the point-dipole representation, relative to charge redistribution, is its ability to capture out-of-plane polarization, the inducible dipole response model causes it to be less accurate than optimal charge redistribution for out-of-plane induction of the planar nitrobenzene molecule. Thus, the widely used inducible dipole response function falls short of the full potential accuracy achievable with the point-dipole representation it employs. Additional results reported here bear on the relative accuracy of self-consistent inducible dipoles versus that of the first-order, or direct, approximation and on methods for assigning partial atomic charges for use in conjunction with inducible dipole models. In sum, these results point to the improvement of polarization response models as an important direction for future research aimed at improving the accuracy of molecular simulations.