DFTB/MM implementation DFTB/MM in PBC has been implemented in a development version of GAMESS-US (2021 R2 Patch 2) interfaced with Tinker 8.10.1. In summary, the QM contribution to the external potential depends on the QM density due to the Mulliken charges that appear in the replica cells. As a consequence, at each SCF step, the external potential is updated and included in the Kohn-Sham Hamiltonian until convergence. The long-range part of the potential is computed using the standard sPME algorithm as implemented in Tinker, from which the value of the external potential at the position of the QM (and, eventually, link atom) centers is extracted. When the electronic density reaches convergence, it is possible to compute the final set of Mulliken charges, construct the converged QM external potential, and compute the total energy and gradient of the system (Eq. 10).