Subtracting 100 from the activation energy ensures that all scores are negative as the calculated electronic activation energy typically ranges between -40 and 20 kcal • mol -1 . Without subtraction from the activation energy, most molecules in a randomly selected starting population will have a positive activation energy which would then be multiplied with the modified SA score ranging between 0 and 1 to give the final score which then would often be positive. This score could be easily minimised by generating molecules that are not synthesisable, therefore giving a modified SA score of 0 which again gives an overall score of 0. Hence, the GA could get trapped in an area of chemical space with low synthesisability and scores close to 0. With the subtraction, virtually all overall scores will be negative and the only way to minimise the score further is to increase the modified SA score while simultaneously decreasing the activation barrier.