We emphasize that our model takes into account the full mutual polarization of QM/MM systems. Our test case systems, the QM and MM subsystems, contain complete fragments, meaning there are no chemical bonds crossing the QM/MM boundary. For the cases with covalent bonds between QM and MM atoms, a link-atom or similar approach can be added straightforwardly. The periodic treatment is applied only to the MM subsystem through the periodic boundary conditions implemented in Tinker-HP. Periodic treatment of the full QM/MM system could be enabled by assigning a multipolar expansion to the QM atom sites and communicating them to Tinker-HP, thus treating the periodicity of the complete system classically through the AMOEBA electrostatics. However, this is out of scope of this study.