Toward the quantitative prediction of T-cell epitopes: CoMFA and CoMSIA studies of peptides with affinity for the class I MHC molecule HLA-A*0201

A set of 102 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 indices analysis (CoMSIA). A test set of 50 peptides was used to determine the predictive value of the models. The CoMFA models gave q2 and r2pred below 0.5. The best CoMSIA model has q2 = 0.542 and r2pred = 0.679, and includes hydrophobic, steric, and H-bond donor fields. 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 three positively contributing physicochemical properties:  local hydrophobicity, steric bulk and hydrogen-bond-donor ability.