An Imbalance in the Force: The Need for Standardized Benchmarks for Molecular Simulation.

Force fields (FFs) for molecular simulation have been under development for more than half a century. As with any predictive model, rigorous testing and comparisons of models critically depends on the availability of standardized data sets and benchmarks. While such benchmarks are rather common in the fields of quantum chemistry, this is not the case for empirical FFs. That is, few benchmarks are reused to evaluate FFs, and development teams rather use their own training and test sets. Here we present an overview of currently available tests and benchmarks for computational chemistry, focusing on organic compounds, including halogens and common ions, as FFs for these are the most common ones. We argue that many of the benchmark data sets from quantum chemistry can in fact be reused for evaluating FFs, but new gas phase data is still needed for compounds containing phosphorus and sulfur in different valence states. In addition, more nonequilibrium interaction energies and forces, as well as molecular properties such as electrostatic potentials around compounds, would be beneficial. For the condensed phases there is a large body of experimental data available, and tools to utilize these data in an automated fashion are under development. If FF developers, as well as researchers in artificial intelligence, would adopt a number of these data sets, it would become easier to compare the relative strengths and weaknesses of different models and to, eventually, restore the balance in the force.

Theoretical Infrared Spectra: Quantitative Similarity Measures and Force Fields.

Infrared spectroscopy can provide significant insight into the structures and dynamics of molecules of all sizes. The information that is contained in the spectrum is, however, often not easily extracted without the aid of theoretical calculations or simulations. We present here the calculation of the infrared spectra of a database of 703 gas phase compounds with four different force fields (CGenFF, GAFF-BCC, GAFF-ESP, and OPLS) using normal-mode analysis. Modern force fields increasingly use virtual sites to describe, e.g., lone-pair electrons or the σ-holes on halogen atoms. This requires some adaptation of code to perform normal-mode analysis of such compounds, the implementation of which into the GROMACS software is briefly described as well. For the quantitative comparison of the obtained spectra with experimental reference data, we discuss the application of two different statistical correlation coefficients, Pearson and Spearman. The advantages and drawbacks of the different methods of comparison are discussed, and we find that both methods of comparison give the same overall picture, showing that present force field methods cannot match the performance of quantum chemical methods for the calculation of infrared spectra.