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 TSs converge to the target structure. Despite these limitations, this first approach provides a valuable starting point for tackling the TS prediction problem. The final distance-matrix approach, developed by Choi, predicted the interatomic distances of a TS structure using the reactant and product structures combined with a linear interpolation between the two. Through different methodologies, all three of the discussed approaches have predicted or generated a guess of the TS geometry using a distance or Coulomb matrix, before converting this matrix back to Cartesian coordinates through some form of optimisation. However, all methods required costly QM optimisations to achieve high accuracy TS geometries, and some even had poor convergence in TS optimisations despite using the guess TS as the starting structure. Additionally, a limitation across all methods was the molecular representation itself. The use of distance and Coulomb matrices occasionally generated TS geometries which did not geometrically resemble the target TS, due to the inability of these representations to encode the spatial orientation of atoms (see Figure ). This highlights the need for molecular representations which utilise Cartesian coordinates directly for more reliable TS predictions.