Hydrogen-bond donors, however, fell recently under scrutiny, as they can impede bioavailability and solvation and should therefore be limited, especially in the early stage of hit-and lead-development. In this regard, 86% of the fragments have only one or zero donors (Figure ). All fragments also show desired medium lipophilicity and polarity, with all logP values below three and only four fragments having a TPSA larger than 60 Å 2 (Figure & F). Also, the focus on solubility during the design stage shifts the distribution of the logS distinctly towards higher values in contrast to the in-stock library (Figure ). This results in high RO3 compliance as only 11% of the members violate one rule (Figure ). In the past, fragment libraries used to be primarily flat and two-dimensional. Recently, though, there has been a rising attentiveness to escape from this "flatland". Even though using more three-dimensional fragments can result in lower hit rates due to the increased complexity and impede synthetic tractability, a certain degree can also help introduce more diversity and improve the solubility and selectivity of hits. In this regard, almost all fragments of the Core Library have at least one rotatable bond and a median fraction of sp hybridised carbon atoms of 32% (Figure A & B). This is also reflected in the principal moments of inertia plot (Figure ). Almost all of the fragments have some degree of "spherelikeness", even though they are close to the "Rod"-"Disc" axis. However, this should be an intuitive observation, as FBDD deals with small and less complex molecules. As rings are ubiquitous in drug design, it is not surprising that all fragments contain at least one ring. Most of the rings being aromatic contributes to the somewhat limited three-dimensionality, primarily due to the focus on sociability (Figure D, E & F).