Panel b) and c) of Figure display in some detail the effect of the inclusion of specific LJ interactions and how they are handled within the new Route II. In fact, by comparing the original QM profiles with those corrected for non-bonded interactions according to equation (11), the significant role of these interactions in reshaping the curves becomes evident. Moreover, as expected, the effect of the specific interactions is generally repulsive, as the corrected profiles consistently appear at lower energies compared to the original values when non-bonded terms are considered. Finally, it is worth noticing how the corrected curves are well reproduced (gray symbols and brown dashed lined in both panels) by the flexible torsional valence term (9), while the original QM profiles is recovered when the whole QMD-FF is relaxed (green symbols and lines, respectively). Turning to the comparison of the results obtained with those delivered from the two general purpose FFs, Figures 7, S13, S14 and S20 show how the QMD-FF outperforms the one computed for both transferable FFs, when they are compared with QM data. Figure clearly shows that GAFF and OPLS miss or displace some minima, and provide generally overestimated barriers, while this in turn reflects in internal energy landscapes significantly dif-ferent from those obtained at QM level (see for instance Figure ). As a final validation, Figure .d shows the results of the same test conducted for the previous molecules, namely verifying that the molecular conformations sampled by the target molecule during gas-phase dynamics are indeed accessible under the given thermodynamic conditions. This is determined by checking if their QM internal energy falls within the range predicted by the virial theorem.