The authors identify the key limitations of the model as being its inability to capture the orientation between groups when there are large distance changes between the reactant and product structures, which would be exacerbated as the system increases in size and flexibility, and the tendency of the model to produce mirror images of the TS, as the distance matrix representation cannot distinguish between these (see Figure ). However, the primary shortcoming of this approach is the requirement for expensive DFT optimisation of the TS guesses produced and also that only 71 % of the predicted