QSAR Study on Antioxidant Tripeptides and the Antioxidant Activity of the Designed Tripeptides in Free Radical Systems

In this study, quantitative structure-activity relationship (QSAR) models were determined based on 91 antioxidant tripeptides. We firstly adopted the stepwise regression (SWR) method for selecting key variables without autocorrelation and then utilized multiple linear regression (MLR), support vector machine (SVM), random forest (RF), and partial least square regression (PLS) to develop predictive QSAR models based on the screened variables. The results demonstrated that all the established models have good reliability (R(2)(train) > 0.86, Q(2)(train) > 0.70) and relatively good predictability (R(2)(test) > 0.88). The contribution of amino acid residues was calculated from the stepwise regression combined with multiple linear regression (SWR-MLR) method model that shows Trp, Tyr, or Cys at C-terminus is favorable for antioxidant activity of tripeptides. Nineteen antioxidant tripeptides were designed based on SWR-MLR models, and the antioxidant activity of these tripeptides were evaluated using three antioxidant assays in free radical systems (1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity, trolox equivalent antioxidant capacity assay, and the ferric reducing antioxidant power assay). The experimental antioxidant activities of these tripeptides were higher than the calculated/predicted activity values of the QSAR models. The QSAR models established can be used to identify and screen novel antioxidant tripeptides with high activity.