For CV in methanol, the chromophore was solvated in a pre-equilibrated solvent sphere of 32 Å, containing 1887 methanol molecules. The system was heated to 300 K using a Langevin thermostat with a collision frequency of 1 ps -1 , followed by a 100 ps equilibration under open boundary conditions. A 26 ps QM/MM trajectory was then generated, with the temperature held at 300 K using the Langevin thermostat. CV was treated at the QM level using the ωb97x 68 functional with the 6-31+G* basis set. The first 2 ps of the trajectory were discarded to allow for additional equilibration after switching the chromophore from the MM to the QM Hamiltonian. This procedure was repeated three times to obtain three independent trajectories. The 100 ps equilibration was carried out each time with different random number seeds, such that the QM/MM dynamics was started with different initial configurations of the system.