Benchmarking crystal structure refinement: A systematic study on Hirshfeld atom refinement

This study systematically investigates the influence of various parameters of the wavefunction calculation during Hirshfeld atom refinement (HAR). We aim to address the lack of consensus in the literature and conflicting information on a generally recommended procedure. A set of amino acid test structures, known for their immense biochemical importance and unimpeachable experimental data quality, was employed to ensure reliable results, unbiased by the question of insufficient diffraction data quality. A comprehensive permutation of refinement parameters was conducted to avoid overlooking potential influences, resulting in 2496 structure refinements per amino acid. Applying a solvent model systematically improved refinement results compared to gas-phase calculations. Additionally, it was observed that the pure Hartree-Fock method outperforms all tested density functional theory methods across all structures in this test set of polar-organic molecules. These findings underscore the importance of carefully considering the level of theory applied in HAR and offer an overview of the performance of various methods and parameters.