To also take the uncertainty associating with the level of theory selection and conformational sampling into account, a soft margin of 1 kcal/mol was used for selecting candidates for further reaction exploration. For example, the difference between the overall barriers of intermediates 4-5 and 4-6 is only 0.3 kcal/mol (32.15 and 32.45 kcal/mol, respectively), thus both intermediates were considered reactants for the fourth-layer reaction exploration. Accounting for the soft margin sometimes led to the effective beam count being greater, but never less than five.