3D-QSAR study on the HLA-A*0201 restricted CTL epitope

A set of 50 peptides with affinity for the class I MHC HLA-A * 0201 molecule was subjected to three-dimensional quantitative structure-affinity relationship (3D QSAR) studies using comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). A test set of 15 peptides was used to determine the predictive potential of the models. The results show that the CoMSIA models are better than the CoMFA models. The CoMFA models gave q(2) and r(pred)(2) below 0.5. The best CoMSIA model has q(2) = 0.628 and r(2) = 0.9979, and includes hydrophobic and steric fields, which were used to predict the binding affinity of 15 samples in the test set with good result r(pred)(2) = 0.743. The results show that the hydrophobic interactions play a dominant role in peptide MHC molecule binding. CoMSIA coefficient contour maps were used to analyze the structural features of the peptides accounting for the affinity in terms of the positively contributing physicochemical properties: local hydrophobicity and steric bulk. The results also provide useful information for structure modification of CTL epitope and theory base for molecular design of therapeutic vaccine.