Moreover, one can control linker flexibility through the "linker ratio of rotatable bonds" component which is defined as the number of rotatable bonds (as calculated by RDKit 46 ) over the total number of bonds (Fig. ). We note that this treatment of flexibility is not the only valid definition and inherent limitations exist such as being completely agnostic to intra-molecular hydrogen bonds. Furthermore, RDKit's calculation of rotatable bonds does not consider bonds to terminal atoms rotatable as it depends on the hybridization of the atom it is attached to. Consequently, bonds to attachment points are always considered non-rotatable. This is exemplified in Fig. where the butane linker receives a ratio of 60/100. Consequently, a linker can never achieve a ratio of rotatable bonds of 100 and to achieve a higher ratio, linkers must become increasingly longer which can lead to unrealistic ideas being proposed.