The system was submitted to 300 ns of production runs, under NPT ensemble at 1 bar using the Martyna-Tuckerman-Klein (MTK) barostat and 300 K using the Nose-Hoover thermostat. Electrostatic forces were calculated with the smooth PME method using a 9 Å cut-off, while constraints were enforced with the M-SHAKE algorithm. Integration was done every 2 fs, with a recording interval of 50 ps. All protein-ligand complexes were submitted to the "Relax model system" using the default parameters. The quality of the simulation and trajectory analyses were carried out with the tools implemented in the Maestro-GUI (Schrödinger, New York, NY, USA). SAM was used as a procedure control, 150 ns of production were generated using the same protocol described in this section.