Theoretical and Computational Chemistry

Improving force field accuracy by training against condensed phase mixture properties



Developing a sufficiently accurate classical force field representation of molecules is key to realizing the full potential of molecular simulation as a route to gaining fundamental insight into a broad spectrum of chemical and biological phenomena. This is only possible, however, if the many complex interactions between molecules of different species in the system are accurately captured by the model. Historically, the intermolecular van der Waals (vdW) interactions have primarily been trained against densities and enthalpies of vaporization of pure (single-component) systems, with occasional usage of hydration free energies. In this study, we demonstrate how including physical property data of binary mixtures can better inform these parameters, encoding more information about the underlying physics of the system in complex chemical mixtures. To demonstrate this, we re-train a select number of the Lennard-Jones parameters describing the vdW interactions of the OpenFF 1.0.0 (Parsley) fixed charge force field against training sets composed of densities and enthalpies of mixing for binary liquid mixtures as well as densities and enthalpies of vaporization of pure liquid systems, and assess the performance of each of these combinations. We show that retraining against the mixture data almost universally improves the force field's ability to reproduce both pure and mixture properties, reducing some systematic errors that exist when training vdW interactions against properties of pure systems only.

Version notes

This version adds additional benchmarks against solvation free energies, as well as new metrics for force field performance for all benchmark physical properties. The introduction has also been updated with additional context.


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Supplementary material

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Supporting Information for "Improving force field accuracy by training against condensed phase mixture properties"
Supporting information for the paper "Improving force field accuracy by training against condensed phase mixture properties". Includes description of the property selection process for the test set (SI Section 1), changes in parameter values, training set performance, and optimization objective function (SI Section 2), test set performance (SI Section 3) and an experimental data error (SI Section 4).