Although fine-tuning the polarization damping (ε in equation ( )) could improve results further, we believe the present level of accuracy is satisfactory for such a simple polarization model. More sophisticated approaches, such as on-the-fly prediction of atomic polarizabilities or a full Thole induction model, may offer further refinements. However, implementing these enhancements falls beyond the scope of this work, especially given that additional issues can arise when deploying these methods in specific workflows (e.g., free energy calculations, virtual screening, or assessing the influence of protein or ligand modifications on binding free energies). Overall, our findings show that ML/MM simulations exhibit consistent and reliable behavior while providing a physically accurate representation of protein-ligand interactions, demonstrating their potential for use in in silico drug design pipelines.