The system is composed of 204,687 atoms where the RSB moiety, formed by 63 atoms, forms part of the QM subsystem. This subsystem is modeled using the BLYP exchange-correlation (XC) functional 48 including Grimme's van der Waals D3 correction 49 using the new driver for the calculation of the XC energy as implemented in the CPMD code. Troullier-Martins norm-conserving pseudopotentials described the valence-core electron interactions. The Poisson's equation was solved with the Martyna-Tuckerman method 52 to ensure isolated system conditions for the QM subsystem. This method requires the size of the QM to be the extent of the RSB moiety plus 3 Å border and twice the size of the electron charge distribution. This results in an orthorhombic QM unit cell with dimensions of a = 92.6, b = c = 62.58 A.U. The MM subsystem is described by the same force fields as in the classical MD simulations. All classical electrostatic interactions were computed within periodic boundary conditions employing the same cutoff for the short-range nonbonded interactions as in the classical MD simulations and particle mesh Ewald 34 for the long-range. Minimum image convention without periodic repetition was employed for the electrostatic QM-MM interactions. The electrostatic QM-MM interactions are calculated using a cut-off distance criteria as implemented in MiMiC: All interactions involving MM atoms within that cutoff are computed directly from the QM electron density. Long-range interactions for MM atoms located further from that cutoff are calculated via a multiple expansion of the QM subsystem. The fragment-based scheme was used in this work, which uses the distances between the center of mass of the fragments in the MM subsystem and the centroid of the QM subsystem. The effect of different short-range cutoffs and multiple orders in the energy and forces was investigated, as shown in the results section. The QM boundary atom is the C α atom of the RSB moiety (Fig. ). This atom is replaced by monovalent pseudopotentials. The MiMiCPy python library 54 was used to prepare the input files.