File Name : figure_s1.png

Caption : the plot shows the benchmarking study between pbe and pbe0 functionals with different basis sets, dzvp-gth , tzvp-gth, and tzv2p-gth. the structures show a higher and lower energy state of bond b4, defined by the bond in its equilibrium position (0.15 nm) and a stretched position (0.21 nm) for fentanyl. we computed the energy difference between those two states.

File Name : figure_s2.png

Caption : the change in free energy as a function of time throughout the simulation for
furanyl fentanyl. the fmax − fmin is the difference in the free energy between the energy
barrier and the global minimum at 0 kj/mol. this quantity is computed in the interval of
every 2 picoseconds. the energy converges early, suggesting that the simulation is converged,
too.

File Name : figure_s3.png

Caption : the change in free energy as a function of time throughout the simulation for o-
fluoro fentanyl. the fmax −fmin is the difference in the free energy between the energy barrier
and the global minima (which is 0 kj/mol). this quantity is computed in the interval of
every 2 picoseconds. the energy converges early, suggesting that the simulation is converged,
too