Towards Automated Benchmarking of Atomistic Forcefields: Neat Liquid Densities and Static Dielectric Constants from the ThermoML Data Archive

TL;DR

This paper demonstrates the feasibility of automating the benchmarking of atomistic forcefields using the machine-readable ThermoML data archive, focusing on liquid densities and dielectric constants to evaluate forcefield accuracy.

Contribution

It introduces a method for automated benchmarking of forcefields against experimental data from ThermoML, reducing manual effort and errors in data compilation.

Findings

Fixed-charge forcefields struggle with low dielectric environments.

Automated data extraction from ThermoML is feasible and effective.

Benchmarking reveals limitations of GAFF in certain conditions.

Abstract

Atomistic molecular simulations are a powerful way to make quantitative predictions, but the accuracy of these predictions depends entirely on the quality of the forcefield employed. While experimental measurements of fundamental physical properties offer a straightforward approach for evaluating forcefield quality, the bulk of this information has been tied up in formats that are not machine-readable. Compiling benchmark datasets of physical properties from non-machine-readable sources require substantial human effort and is prone to accumulation of human errors, hindering the development of reproducible benchmarks of forcefield accuracy. Here, we examine the feasibility of benchmarking atomistic forcefields against the NIST ThermoML data archive of physicochemical measurements, which aggregates thousands of experimental measurements in a portable, machine-readable, self-annotating format. As a proof of concept, we present a detailed benchmark of the generalized Amber small molecule forcefield (GAFF) using the AM1-BCC charge model against measurements (specifically bulk liquid densities and static dielectric constants at ambient pressure) automatically extracted from the archive, and discuss the extent of available data. The results of this benchmark highlight a general problem with fixed-charge forcefields in the representation low dielectric environments such as those seen in binding cavities or biological membranes.