Learnings from quantitative structure-activity relationship (QSAR) studies with respect to food protein-derived bioactive peptides: a review

The generation of bioactive peptides (BAPs) from dietary proteins has been widely studied. One of the main limitations of a broader application of BAPs in functional foods may arise from their low potency. Therefore, the search for more potent structures is crucial. Quantitative structure-activity relationship (QSAR) has been widely applied in drug discovery and some examples may also be found in the study of BAPs. The aim of this review was to assess the efficiency of QSAR for the discovery of novel and potent BAPs, derived from food protein sources. A wide range of bioactive properties including antioxidant, antimicrobial, angiotensin converting enzyme (ACE), renin and dipeptidyl peptidase IV (DPP-IV) inhibition as well as bitter peptides has been investigated with QSAR. Some studies have identified structural requirements for specific bioactivities, which generally confirmed findings from earlier studies carried out on those BAPs. However, discrepancies are found across analyses, possibly due to the quality of the peptide datasets as well as the descriptors used to build QSAR models. It appears to date that only a limited number of QSAR studies conducted with BAPs have subsequently carried out confirmatory studies and evaluated promising peptide sequences in vivo. This suggests that more research is needed in order to advance knowledge in the area of BAP discovery using QSAR.