The FE profiles of the acylation and deacylation steps were obtained by first applying WTMD along the HLDA reaction coordinate at the DFTB3 level and subsequently calculated using statistical reweighting. To assess the structural properties of the stable and metastable structures produced in course of the reaction, the representative configurations correlating with FE minima were extracted and simulated for 50 ps under the same conditions as those used for WTMD simulations. With this procedure (i) the average properties of these structures were extracted under equilibrium conditions and (ii), it was verified that the metastable states corresponding to putative reaction intermediate are stable in the absence of external biases. The average values of the descriptors calculated with this procedure are reported in Table and Table , and they are used to comment the progress of the two reaction stages in the following sections. The definition of each descriptor can be found in Table and illustrated in Figure , whereas the relevant atoms are highlighted in Figure .