Shape and electrostatic properties of molecules are primary determinants of molecular recognition and should consequently be the method of choice when comparing the similarity of molecules encountered at various stages in drug design. Even though these methods have been used to achieve major impacts in related areas (e.g., virtual screening leading to the discovery of novel and unexpected chemotypes ), they have been largely unexplored in the context of de novo generative methods, although promising attempts have been made. One reason for the reluctance of using 3D methods is the challenge of obtaining accurate descriptions of molecules bioactive conformations. In this work, we reduce this notoriously difficult step by using 3D-fragments of the complete target compounds.