# The Structure-Activity Relationship of the Antioxidant Peptides from Natural Proteins
## 4 Systematic Schemes to Predict the Antioxidative Activity of Peptides  
The bioactivity of peptides may result from their chemical structure. Recently, a quantitative structure-activity relationship (QSAR) scheme as an application of chemometric and bioinformatics methods has been used [62]. It has been used extensively in this context in the fields of medical science and toxicology [33; 55; 63]. The characteristic chemical structure of antioxidant peptides can be predicted by a model expressed as a mathematical expression for the relationship between structure and activity. It may be a useful tool to evaluate food proteins as potential precursors of bioactive peptides and to predict the possible release of bioactive peptides from various proteins using proteolytic enzymes with different specificity. QSAR models involving antioxidant peptides have been established [33; 63]. [PERSON] and coworkers reported that by QSAR models with the FRAD assay, some structural characteristics, including electron and hydrogen-bonding properties of the amino acids, the steric properties of the amino acid residues at the C- and \(N\)-termini and the neighboring amino acids of the Cys or Trp units are predicted to play an important role in the antioxidant activities of the tripeptides from \(\beta\)-lactoglobulin [33]. [PERSON] and [PERSON] have also successfully predicted the relationship of the C-terminal and \(N\)-terminal regions and antioxidant potency using QSAR models with three databases, namely, Trolox-equivalent antioxidant capacity (TEAC), oxygen radical absorption capacity (ORAC), and superoxide radical (SOR) [55]. For predicting antioxidant activity, the properties of amino acids at the C-terminal regions were found more important than those at the N-terminal regions. The electronic donating ability is found to significantly influence the antioxidant activity in the three free radical systems. Furthermore, their synergistic effects are displayed notably at each position. Bulky hydrophobic amino acids at the C-terminal were related to the antioxidant activity of peptides in the three free radical systems. Some TEAC databases show the probable influence of stericity in the N-terminal segment (N2, N3) and the activity exists [53].  
Bioinformatics, as well as QSAR models, can provide insight at the molecular level of specific peptide sequences. Most limitations on the application of QSAR in exploring antioxidant peptides from protein hydrolysates cannot be neglected. The distinguishing features for using the bioinformatics methods is heavily dependent on the relative data. The results reported in the field mainly focus on tripeptides for their simple structures. Since only peptides with the same number of amino acids were used to illustrate the QSAR modeling, the knowledge of the structure-activity relationships of peptideslonger than four amino acids is far from being accessible as the process becomes more complicated with longer peptides. Further investigations are often limited by the high cost of chemical synthesis of longer peptides, which may involve cross-validation tests to objectively evaluate the anticipated accuracy of the predictor. The data in the literature cannot be fully used due to the defects of evaluation assays, nevertheless, it will be a useful tool for initiative and systemic research on antioxidant peptides hydrolyzed from proteins [64].