The model reaction TS is then "aligned" (Fig. ) by replacing the geometries of the reactive part of the selected side with the model reaction TS geometry, followed by constrained forcefield and GFN2-xTB (optional) optimization with the reactive atoms fixed in place. By fixing the reactive atoms and relaxing the rest of the structure, the resulting geometry has the correct connectivity while being close to the TS of the input reaction. For SSIII and SSIV, additional conformational sampling is performed at this stage using CREST, with conformers selected based on GFN2-xTB energies until reaching a user-defined number. Finally, the resulting TS guess or guesses are optimized using standard methods (e.g. Berny optimization or QST3 algorithm ) at the relevant level of theory.