Engineering Transferable Atomic Force Fields: Empirical Optimization of Hydrocarbon Lennard-Jones Interactions by...

The utility of atomistic simulations depends on the accuracy of the force field used to represent the potential energy landscape, the consistency with which interaction parameters can be assigned, and the extent to which parameters can be transferred between chemical entities. Here, parameter space mapping, a simple and robust procedure for atom typing (parameter assignment) and parameter optimization, is used to identify a minimal set of parameters capable of simultaneously reproducing the density, heat of vaporization, and solvation free energies for a targeted set of simple hydrocarbons. Using an atom-centered fixed charge model and a 6-12 Lennard-Jones potential, the experimental densities and the heats of vaporization for 22 hydrocarbons (linear, cyclic, and aromatic) could be predicted with high precision: average unsigned error (AUE) of 6.1 kg/m³ and 0.5 kJ/mol, respectively, and R² values of 0.991 and 0.999, respectively. For the 17 compounds with experimental solvation free energy values in water, the AUE was 1.3 kJ/mol, and the slope and R² for the line of best fit were 0.968 and 0.991, respectively. A key element in ensuring transferability in this work was minimizing confounding variables by ensuring that the calculation of observables was independent of the precise choice of simulation settings (cutoff, bond constraints, etc.) and the explicit consideration of correlations between parameters.