Chemical Space Exploration with Artificial “Mindless” Molecules
Thomas Gasevic, Marcel Müller, Jonathan Schöps, Stephanie Lanius, Jan Hermann, Stefan Grimme, Andreas Hansen
Abstract
We introduce MindlessGen, a Python-based generator for creating chemically diverse, “mindless” molecules through random atomic placement and subsequent geometry optimization. Using this framework, we constructed the MB2061 benchmark set, containing 2061 molecules with high-level PNO-LCCSD(T)-F12 reference data for H 2 -promoted decomposition reactions. This set provides a challenging benchmark for testing, validating, and training density functional approximations (DFAs), semiempirical methods, force fields, and machine learning potentials using molecular structures beyond conventional chemical space. For DFAs, we initially hypothesized that highly parametrized functionals might perform poorly on this set. However, no consistent relationship between the fitting strategy and accuracy was observed. A clear Jacob’s ladder trend emerges, with ωB97X-2 achieving the lowest mean absolute error (MAE) of 8.4 kcal·mol –1 and r 2 SCAN-3c offering a robust cost-efficient alternative (19.6 kcal·mol –1 ). Furthermore, we discuss the performance of selected semiempirical methods and contemporary machine-learning interatomic potentials.