Quantitative structure-activity relationship models for bitter-tasting tripeptides based on integrated descriptors

Abstract

In the present work, three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed in an attempt to predict the key features of bitter-tasting tripeptides. The 3D-QSAR models were carried out by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods and the corresponding statistical correlation coefficients R2cv for the training set are 0.534 and 0.547, respectively, the predicted correlation coefficients R2pred for the test set are found to be 0.7162 and 0.5792, respectively. The information obtained from the QSAR contour maps enables the interpretation of the structure-activity relationship. In addition, molecular docking was also employed to investigate the interaction between bitter-tasting peptides and related receptor hTAS2R1, results indicate that the Lys76, Pro188 and His243 were significant for binding to the peptides, and some essential features were identified to deduce some interesting structure-activity relationships. The present QSAR models along with information contour maps and molecular docking study may be used for designing and predicting novel bitter-tasting peptides.