Background: Saponin metabolism shows high structural variability due to the diversity
of aglycones and glycosylations (Gly). Although they represent a potential source of drug design,
their metabolism remains misunderstood yet due to insufficient investments in analytical methods.
Aims: Bibliographic structural data offer a wide field for extensive statistical analysis, highlighting
mechanistic orders governing metabolic diversity. This work presents an original simulation
method based on simplex rule for highlighting regulatory mechanisms of metabolism from categorical
Methods: Simulation was applied on a set of 231 saponins of the Caryophyllaceae plant family initially
affiliated to four aglycone types: gypsogenin (Gyp), quillaic acid (QA), gypsogenic acid
(GA), and 16-OH-gypsogenic acid (16-OH-GA). Molecules were initially characterized by relative
glycosylation levels of different carbons. Simplex approach was applied by combining saponins of
the four aglycone groups using a complete set of N gradual weightings between structural groups.
In silico combinations were applied by randomly sampling representative saponins from the four
groups conforming to their weights given by mixture design. Gly profiles of sampled saponins
were averaged to calculate a barycentric molecular profile for each mixture. With N mixtures, N
barycentric molecules were iteratively calculated by bootstrap, leading to smoothed data from
which Gly trends between carbons were highlighted.
Results: Sequential, competing and cooperative Gly trends were highlighted according to the types
of aglycones, attached saccharides and positions of substituted carbons. Such various conditional
Gly trends seemed to be linked to multiple factors, including steric effects, regio-selectivity, enzymatic
specificity and enzymatic promiscuity. These simulated results could be helpfully useful in
chemical synthesis and drug design.
Conclusion: These simulated results could usefully help for chemical syntheses and drug design.