Focusing on the rRNA:M5 interface, our simulated model comprised the M5 enzyme, the UL18 cofactor (PDB chain h) and part of the rRNA chain (PDB chain V), selecting a 104-nucleotide portion (5 ′ strand up to residue U72, and 3 ′ strand up to A99) relevant for the interaction with M5 (see Figure ). A loop (sequence G-G-U-A-U-G-A-G from 5 ′ to 3 ′ ) was then added using RNA Composer to avoid fraying of the RNA ends. Using Gromacs tools, this rRNA:protein complex was then immersed in a 130 Å box of water molecules with a background NaCl concentration of 150 mM. Force fields. Proteins were described with the ff14SB force field, and RNA with the amberff99-bsc0-χ OL3 force field. These force fields were combined with the TIP3P water model 27 and Joung-Cheatham parameters for monovalent ions. The stability of the active site structure was tested using 3 different force field for Mg 2+ : the non-polarizable full charge model proposed by Merz and coworkers "Mg m " (TIP3P CM set version); the parametrization proposed by Schwierz and coworkers 30 (TIP3P version) with pair-specific Lennard-Jones parameters to capture the Mg 2+ -phosphate interaction strength; and our scaled charge "Electronic Continuum Correction" (ECC) force field, with a charge reduced to +1.6 on both Mg 2+ atoms. The ECC approach is a mean-field strategy that takes into account electronic polarization as a dielectric continuum, which is formerly equivalent to scaling ionic charges by a factor 1/ √ ϵ ∞ ∼ 0.75 in water. This approach has been found very promising to describe electrolyte solutions and capture ion pairing to phosphate moieties, where a scaling factor of 0.8 was found more appropriate. We used this force field in combinaison with the SPC/E water model, that it was developed to be compatible with.