In Figure , we show the time record of the T 1 and T 2 dihedral angles during a 128 ns long standard MD simulation of compound 2. We observed one naphtyl flipping as probed by T 1 and no flipping for the methylene connected naphtyl moieties during the entire simulation. Standard MD is apparently unable to reliable sample the conformational states of compound 2 even extending In Figure we finally show the PMF obtained for the torsional potential of the T 1 (black color lines) and T 2 (green color lines) dihedral angles using standard MD and replicates of much shorter standard MD simulations. In the Figure, the PMF obtained with the adaptive HREM (in blue and cyan color) is also superimposed for comparison. For the T 1 torsion, characterized by a barrier of 5 kcal/mol, we notice that the statistics collected in the 8 replicates MD simulations (128 ns in total) produces a PMF that closely follows that obtained with the 16 ns of HREM simulation. For the T 2 , standard MD simulations, whether using short replicates or a single long lasting run, are unable to sample the secondary minimum detected in HREM at θ = 60 • , showing the limitations of the straightforward replicates approach when dealing with long-lived metastable states.