One of the most frequently used descriptors to quantify molecular flexibility is the number of rotatable bonds. Though common, this descriptor does suffer from a number of drawbacks. Perhaps the largest of these is that it requires a clear, and ideally easily computed, definition of which bonds are rotatable. There are many of such definitions, e.g., the one proposed by Bath et al. , but not one used by all. Furthermore, the number of rotatable bonds, being constrained to integer values, provides a very coarse-grained view of the size of the conformational space and ignores the fact that different types of bonds have different degrees of rotational freedom. To overcome these challenges, Kier developed the φ index , which provides a continuous description of the flexibility space derived solely based upon information from the molecular graph. While being an improvement in comparison to the number of rotatable bonds, the Kier φ does not resolve all issues as it is unable to distinguish stereo-and regioisomers , and, as we will discuss below, is not particularly effective when used to estimate the size of the conformational space for a molecule.