Speed up Multi‐Scale Force‐Field Parameter Optimization by Substituting Molecular Dynamics Calculations with a Machine Learning Surrogate Model

Molecular modeling plays a vital role in many scientific fields, ranging from material science to drug design. To predict and investigate the properties of those systems, a suitable force field (FF) is required. Improving the accuracy or expanding the applicability of the FFs is an ongoing process, referred to as force‐field parameter (FFParam) optimization. In recent years, data‐driven machine learning (ML) algorithms have become increasingly relevant in computational sciences and elevated the capability of many molecular modeling methods. Herein, time‐consuming molecular dynamic simulations, used during a multiscale FFParam optimization, are substituted by a ML surrogate model to speed‐up the optimization process. Subject to this multiscale optimization are the Lennard–Jones parameters for carbon and hydrogen that are used to reproduce the target properties: n ‐octane's relative conformational energies and its bulk‐phase density. By substituting the most time‐consuming element of this optimization, the required time is reduced by a factor of ≈20, while retaining FFs with similar quality. Furthermore, the workflow used to obtain the surrogate model (i.e., training data acquisition, data preparation, model selection, and training) for such substitution is presented.