We start by considering a very simple search problem for which the various factors contributing to successful searches can be demonstrated analytically (see SI). The sentence "to be or not to be that is the question" has 39 lower case characters including spaces. It is one of 27 39 = 6.7×10 55 39-character sequences, which is roughly the same size as chemical space. Despite this vast search space a simple genetic algorithm (GA) can easily identify the target: using an initial population of 100 randomly generated phrases and a mutation rate of 20% the target phrase is identified after no more than ∼300 generations (median ∼200), i.e. the solution is consistently found by evaluating only ca 10,000 to 30,000 sequences out of 6.7× 10 55 possible (Figure )