Table 2 Helper functions from PKS_Enumerator class. The descriptions for each function were provided to help understand the workflow of PKS Enumerator provided in Fig. 7

Binary search function (F_BS)

Searches target item in the given list. Implemented to ensure no duplicate macrocycles are generated

Descriptor computing function (F_DC)

Computes six molecular descriptors for the input compound via RDKit library: Molecular Weight—MW, Hydrophobicity—SlogP, Hydrogen Bond Acceptors—HBA, Hydrogen Bond Donors—HBD, Topological Polar Surface Area—TPSA, and Rotatable Bonds—NRB

Length pair function (F_LP)

Generates all possible common and rare SM length arrangements based on total number of SMs allowed in the program. This method is reliant on parameters 1, 2, 3, 4, 5, 6 and 7 in the building rules. The length pairs returned are sorted based on ascending number of either common or rare structural motifs (7th parameter). Default prioritizes CSMs, i.e. length pairs are sorted based on ascending lengths of rare SMs, thereby prioritizing CSMs in the macrocycles. In each length pair, the number of CSMs are noted as L_C and RSMs as L_R. Their sum provides the total number of SMs per macrocycle

Combination function (F_C)

Generates all different combinations of SMs per input length