Quantitative Structure–Activity Relationship Study of Bitter Di-, Tri- and Tetrapeptides Using Integrated Descriptors

New quantitative structure–activity relationship (QSAR) models for bitter peptides were built with integrated amino acid descriptors. Datasets contained 48 dipeptides, 52 tripeptides and 23 tetrapeptides with their reported bitter taste thresholds. Independent variables consisted of 14 amino acid descriptor sets. A bootstrapping soft shrinkage approach was utilized for variable selection. The importance of a variable was evaluated by both variable selecting frequency and standardized regression coefficient. Results indicated model qualities for di-, tri- and tetrapeptides with R2 and Q2 at 0.950 ± 0.002, 0.941 ± 0.001; 0.770 ± 0.006, 0.742 ± 0.004; and 0.972 ± 0.002, 0.956 ± 0.002, respectively. The hydrophobic C-terminal amino acid was the key determinant for bitterness in dipeptides, followed by the contribution of bulky hydrophobic N-terminal amino acids. For tripeptides, hydrophobicity of C-terminal amino acids and the electronic properties of the amino acids at the second position were important. For tetrapeptides, bulky hydrophobic amino acids at N-terminus, hydrophobicity and partial specific volume of amino acids at the second position, and the electronic properties of amino acids of the remaining two positions were critical. In summary, this study not only constructs reliable models for predicting the bitterness in different groups of peptides, but also facilitates better understanding of their structure-bitterness relationships and provides insights for their future studies.