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The development of Enamine\u2019s REAL Space has shown that large spaces of readily available compounds may be created this way. These are several orders of magnitude larger than previous libraries. So far, searching and navigating these spaces is mostly limited to topological approaches. A way to overcome this limitation is optimization via metaheuristics which can be combined with arbitrary scoring functions. Here we present Galileo, a novel Genetic Algorithm to sample fragment spaces. We showcase Galileo in combination with a novel pharmacophore mapping approach, called Phariety, enabling 3D searches in fragment spaces. We estimate the effectiveness of the approach with a small fragment space. 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