Hamiltonian. As reference, we carried out QM/MM molecular dynamics simulations with the adaptive string method at the M06-2X/def2-SVP/CHARMM36 level of theory. corrections on the optimized DFTB3 profile, with a barrier of only 1.5 kcal/mol higher (see Figure ), while at the enolate region the energies were up to 8.8 kcal/mol higher. Here, it is worth to mention that these deviations are similar to the ones in the QM/MM potential energy profiles (see Figure ). On the other hand, the corrected profile in red showed good agreement with the profile obtained at the M06-2X/def2-SVP/CHARMM36 level of theory.