The activation energy for TMA is found to be 23.4 kcal/mol. Side reactions having activation energies that are lower than or close to this value must thus be considered. This can be done by incorporating knowledge of side reactions in the scoring function of the genetic algorithm e.g. a given catalyst is optimized to both lower the activation energy for the target reaction while simultaneously raising it for side reactions. From the reaction network of TMA, we see that any side reaction needs to go through intermediate 150, 176, 216 or 553 (Figure ). The primary path to intermediates 150, 176 and 216 originates from intermediate 77 while intermediate 553 is formed from intermediate 166 (Figure ). We find neither new meta-MD nor proton-transfer reactions from intermediate 216 -only the back-reaction to intermediate 77 is observed. With a Gibbs free energy 14 kcal/mol higher than the reactants, the system will also not get stuck here meaning that this side-reaction is deemed unimportant. Both intermediates 150 and 176 have high Gibbs free energies close to the activation energy of the MBH reaction; 23 and 20 kcal/mol, respectively. However, if the barriers are low enough they could act as "gateways" to products with lower reaction energies than the MBH product (Figure ). Thus we use a previously published method for finding TS guess structures based on the same kind of biasing potentials used in the meta-MD to find TSs for the reaction between intermediates 77 and 150 and between intermediates 77 and 176 . For the 77 → 176 reaction we find a barrier of 29 kcal/mol. When searching for the 77 → 150 TS, we instead find the TS for the 176 → 150 reaction with a barrier of 25 kcal/mol. Looking at intermediates 150 and 177, it makes sense that the 77 → 150 goes through intermediate 176. Thus, we expect a 29 kcal/mol barrier for getting to either intermediates. Compared to a barrier of 23 kcal/mol for the MBH reaction we do not deem these side-reactions important and ignore them in the GA scoring function. Finally, intermediate 553 has a Gibbs free energy 24 kcal/mol higher than the reactant system. Since the intermediate Gibbs free energy is already higher than the MBH activation energy, this side-reaction is also deemed unimportant.