Open Force Field Evaluator: An Automated, Efficient, and Scalable Framework for the Estimation of Physical Properties from Molecular Simulation

Developing accurate classical force field representations of molecules is key to realizing the full potential of molecular simulations, both as a powerful route to gaining fundamental insights into a broad spectrum of chemical and biological phenomena and for predicting physicochemical and mechanical properties of substances. The Open Force Field Consortium is an industry-funded open science effort to this end, developing open-source tools for rapidly generating new high-quality small-molecule force fields. An integral aspect of this is the parameterization and assessment of force fields against high-quality, condensed-phase physical property data, curated from open data sources such as the NIST ThermoML Archive, alongside quantum chemical data. The quantity of such experimental data in open data archives alone would require an onerous amount of human and computational resources to both curate and estimate manually, especially when estimations must be obtained for numerous sets of force field parameters. Here, we present an entirely automated, highly scalable framework for evaluating physical properties and their gradients in terms of force field parameters. It is written as a modular and extensible Python framework, which employs an intelligent multiscale estimation approach that allows for the automated estimation of properties from simulation and cached simulation data, and a pluggable API for estimation of new properties. In this study, we demonstrate the utility of the framework by benchmarking the OpenFF 1.0.0 small-molecule force field and GAFF 1.8 and GAFF 2.1 force fields against a test set of binary density and enthalpy of mixing measurements curated using the framework utilities. Further, we demonstrate the framework's utility as part of force field optimization by using it alongside ForceBalance, a framework for systematic force field optimization, to retrain a set of nonbonded van der Waals parameters against a training set of density and enthalpy of vaporization measurements.

Automated summary

This study presents a fully automated and highly scalable framework for evaluating physical properties based on force field parameters. The framework utilizes an intelligent multiscale estimation approach and is written in modular and extensible Python.