Clemons et al. found that protein-binding frequency and selectivity increased for small molecules with intermediate proportion of stereogenic carbons, in comparison to compounds with very low and high stereogenic content, indicating FCstereo as an important score for consideration in designing screening libraries. These selectivity results are also supported by other reports noting an improvement of selectivity with the increase in stereochemical complexity. Various 3D descriptors correlate well with compound selectivity, observed solubility and clinical success. However, a major drawback of calculating 3D descriptors is the necessity for accurate prediction of molecular conformations, which can pose a significant computational challenge and cost for the analysis of larger compound libraries.